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No VTE prophylaxis needed after joint surgery in patients with hemophilia
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.
In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.
The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.
“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.
“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.
Skip the heparin?
VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.
Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.
The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.
The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.
As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.
The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).
“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.
The study was internally funded. The investigators reported no conflicts of interest.
AT WFH 2016 WORLD CONGRESS
Key clinical point: Prophylaxis against thromboembolic events after orthopedic surgery in patients with hemophilia may not be necessary.
Major finding: There were no thromboembolic events after joint surgery without anticoagulant prophylaxis in patients with hemophilia A or B.
Data source: Cohort study of 50 patients with hemophilia A or B undergoing major joint replacement surgery.
Disclosures: The study was internally funded. The investigators reported no conflicts of interest.
Hematuria a common finding in pediatric hemophilia
ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.
Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.
“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.
Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.
The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.
They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.
They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.
A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).
Characteristics associated with risk for hematuria included older age and hemophilia A.
Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.
Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.
“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.
Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”
The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.
ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.
Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.
“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.
Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.
The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.
They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.
They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.
A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).
Characteristics associated with risk for hematuria included older age and hemophilia A.
Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.
Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.
“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.
Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”
The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.
ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.
Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.
“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.
Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.
The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.
They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.
They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.
A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).
Characteristics associated with risk for hematuria included older age and hemophilia A.
Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.
Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.
“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.
Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”
The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.
AT WFH 2016 WORLD CONGRESS
Key clinical point:. Hematuria is a common finding in children with hemophilia A or B.
Major finding: Of 93 patients with hemophilia, 43 (47%) had hematuria findings on routine urinalysis.
Data source:. Prospective study in 67 patients with hemophilia A and 26 with hemophilia B.
Disclosures: The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures
Hemophilia may not be protective against CVD
ORLANDO – Conventional wisdom holds that persons with hemophilia are at lower risk for death from cardiovascular events than the general population, but there are conflicting data from studies attempting to confirm or refute this notion.
In a prospective, multicenter European study of more than 500 patients with hemophilia, the predicted cardiovascular disease (CVD) event rate was less than half of what was expected, reported Paul R. van der Valk, MD, from University Medical Center in Utrecht, the Netherlands, and colleagues.
In patients with hemophilia, “the leading cause of death seems to be malignancy related and intracranial hemorrhage. Atrial fibrillation is quite common,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
But a second study of 100 patients with hemophilia showed that the bleeding disorder did not appear to offer protection against cardiovascular or thrombotic adverse events, Beatriz Delgado, MD, and colleagues at the Centro Hospitalar São João in Porto, Portugal, also presented in a poster session.
Risk scores considered
The prospective study by Dr. van der Valk and colleagues was designed to assess the incidence of CVD in patients with hemophilia in the Netherlands and the United Kingdom, compared with the general population. They used the QRISK2 cardiovascular risk score (2011 version). This instrument is used to calculate risk of CVD events in adults from 30 to 84 with no history of CVD or statin use.
Among 557 patients with a calculable QRISK2 score at 2 years of follow-up, there were four CVD events, including two cases of ischemic heart disease, one ischemic stroke, and one intracranial hemorrhage. The median 2-year QRISK2 score was 1.7%, and the 10-year risk was 9.0%, which translated in to an expected 9.5 CVD events during 2 years of follow-up.
Among the additional 104 patients who could not have a QRISK2 score calculated because of age over 84, statin use, or history of CVD, there were four CVD events: ischemic heart disease, transient ischemic attack/carotid artery stenosis, myocardial infarction, and intracranial hemorrhage.
Other CVD events occurring in both groups included atrial fibrillation in eight patients, other arrhythmia in three, and, in one patient each, aortic valve pathology, pericarditis, and carotid artery plaque.
Portuguese experience
Dr, Delgado and colleagues noted that although hemophilia has traditionally been regarded as protective against ischemic heart disease or thrombotic events, modern management “has prolonged life expectancy of people with hemophilia and consequently, an associated increase in incidence and prevalence of conditions that affect the general older population, such as cardiovascular disease and hypertension, are expected.”
They conducted a retrospective analysis of 100 adults (69 with hemophilia A, and 31 with hemophilia B) treated at their center. Overall, 29 patients had severe hemophilia A, 20 moderate hemophilia A, and 20 mild hemophilia A. Among patients with hemophilia B, 11 had severe, 15 moderate, and 5 mild disease.
Two patients (one with moderate and one with severe hemophilia) had angina episodes with coronary artery disease and underwent multiple coronary bypass grafts. The patient with severe disease had a disabling ischemic stroke during recovery from bypass surgery, and the patient with moderate hemophilia had an acute myocardial infarction prior to bypass surgery.
Two other patients had transient ischemic strokes from which they recovered without disability.
The main cardiovascular risk factors identified in this population were hypertension, diabetes mellitus, heavy smoking, obesity, and dyslipidemia. All patients were screened for prothrombotic risk, and all patients had negative test results.
“Hemophilia does not seem to have a protective effect against thrombotic/cardiovascular events, mainly in [patients with] coronary artery disease,” the investigators wrote.
Endothelial function
In a study presented in an oral abstract session, Shannon Jackson, MD, of the University of British Columbia in Vancouver found that men with hemophilia appear to have better macrovascular endothelial function but worse microvascular endothelial function than did men with normal clotting parameters.
“Based on endothelial function, contemporary hemophilia cohorts may have a different profile of cardiovascular risk than healthy controls,” she said.
Although they do not have an obvious mechanistic explanation for the differences in microvascular function among patients with hemophilia vs. healthy controls, there is evidence to show that microvascular function is predictive of cardiovascular events independent of other risk factors in otherwise healthy people. Their findings indicate that further study of the association between endothelial function, cardiovascular risk factors, and atherosclerosis among patients with hemophilia is warranted, she said.
Dr. van der Valk and colleagues and Dr. Delgado and colleagues did not disclose funding or conflicts of interest. The study by Dr. Jackson and colleagues was supported by the Canadian Hemophilia Society and Pfizer. She disclosed honoraria for speaking engagements for Biogen, Baxalta, and Pfizer and for participating in scientific advisory boards for Bayer, Pfizer, Baxalta, CLS Behring, and Novo Nordisk.
ORLANDO – Conventional wisdom holds that persons with hemophilia are at lower risk for death from cardiovascular events than the general population, but there are conflicting data from studies attempting to confirm or refute this notion.
In a prospective, multicenter European study of more than 500 patients with hemophilia, the predicted cardiovascular disease (CVD) event rate was less than half of what was expected, reported Paul R. van der Valk, MD, from University Medical Center in Utrecht, the Netherlands, and colleagues.
In patients with hemophilia, “the leading cause of death seems to be malignancy related and intracranial hemorrhage. Atrial fibrillation is quite common,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
But a second study of 100 patients with hemophilia showed that the bleeding disorder did not appear to offer protection against cardiovascular or thrombotic adverse events, Beatriz Delgado, MD, and colleagues at the Centro Hospitalar São João in Porto, Portugal, also presented in a poster session.
Risk scores considered
The prospective study by Dr. van der Valk and colleagues was designed to assess the incidence of CVD in patients with hemophilia in the Netherlands and the United Kingdom, compared with the general population. They used the QRISK2 cardiovascular risk score (2011 version). This instrument is used to calculate risk of CVD events in adults from 30 to 84 with no history of CVD or statin use.
Among 557 patients with a calculable QRISK2 score at 2 years of follow-up, there were four CVD events, including two cases of ischemic heart disease, one ischemic stroke, and one intracranial hemorrhage. The median 2-year QRISK2 score was 1.7%, and the 10-year risk was 9.0%, which translated in to an expected 9.5 CVD events during 2 years of follow-up.
Among the additional 104 patients who could not have a QRISK2 score calculated because of age over 84, statin use, or history of CVD, there were four CVD events: ischemic heart disease, transient ischemic attack/carotid artery stenosis, myocardial infarction, and intracranial hemorrhage.
Other CVD events occurring in both groups included atrial fibrillation in eight patients, other arrhythmia in three, and, in one patient each, aortic valve pathology, pericarditis, and carotid artery plaque.
Portuguese experience
Dr, Delgado and colleagues noted that although hemophilia has traditionally been regarded as protective against ischemic heart disease or thrombotic events, modern management “has prolonged life expectancy of people with hemophilia and consequently, an associated increase in incidence and prevalence of conditions that affect the general older population, such as cardiovascular disease and hypertension, are expected.”
They conducted a retrospective analysis of 100 adults (69 with hemophilia A, and 31 with hemophilia B) treated at their center. Overall, 29 patients had severe hemophilia A, 20 moderate hemophilia A, and 20 mild hemophilia A. Among patients with hemophilia B, 11 had severe, 15 moderate, and 5 mild disease.
Two patients (one with moderate and one with severe hemophilia) had angina episodes with coronary artery disease and underwent multiple coronary bypass grafts. The patient with severe disease had a disabling ischemic stroke during recovery from bypass surgery, and the patient with moderate hemophilia had an acute myocardial infarction prior to bypass surgery.
Two other patients had transient ischemic strokes from which they recovered without disability.
The main cardiovascular risk factors identified in this population were hypertension, diabetes mellitus, heavy smoking, obesity, and dyslipidemia. All patients were screened for prothrombotic risk, and all patients had negative test results.
“Hemophilia does not seem to have a protective effect against thrombotic/cardiovascular events, mainly in [patients with] coronary artery disease,” the investigators wrote.
Endothelial function
In a study presented in an oral abstract session, Shannon Jackson, MD, of the University of British Columbia in Vancouver found that men with hemophilia appear to have better macrovascular endothelial function but worse microvascular endothelial function than did men with normal clotting parameters.
“Based on endothelial function, contemporary hemophilia cohorts may have a different profile of cardiovascular risk than healthy controls,” she said.
Although they do not have an obvious mechanistic explanation for the differences in microvascular function among patients with hemophilia vs. healthy controls, there is evidence to show that microvascular function is predictive of cardiovascular events independent of other risk factors in otherwise healthy people. Their findings indicate that further study of the association between endothelial function, cardiovascular risk factors, and atherosclerosis among patients with hemophilia is warranted, she said.
Dr. van der Valk and colleagues and Dr. Delgado and colleagues did not disclose funding or conflicts of interest. The study by Dr. Jackson and colleagues was supported by the Canadian Hemophilia Society and Pfizer. She disclosed honoraria for speaking engagements for Biogen, Baxalta, and Pfizer and for participating in scientific advisory boards for Bayer, Pfizer, Baxalta, CLS Behring, and Novo Nordisk.
ORLANDO – Conventional wisdom holds that persons with hemophilia are at lower risk for death from cardiovascular events than the general population, but there are conflicting data from studies attempting to confirm or refute this notion.
In a prospective, multicenter European study of more than 500 patients with hemophilia, the predicted cardiovascular disease (CVD) event rate was less than half of what was expected, reported Paul R. van der Valk, MD, from University Medical Center in Utrecht, the Netherlands, and colleagues.
In patients with hemophilia, “the leading cause of death seems to be malignancy related and intracranial hemorrhage. Atrial fibrillation is quite common,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
But a second study of 100 patients with hemophilia showed that the bleeding disorder did not appear to offer protection against cardiovascular or thrombotic adverse events, Beatriz Delgado, MD, and colleagues at the Centro Hospitalar São João in Porto, Portugal, also presented in a poster session.
Risk scores considered
The prospective study by Dr. van der Valk and colleagues was designed to assess the incidence of CVD in patients with hemophilia in the Netherlands and the United Kingdom, compared with the general population. They used the QRISK2 cardiovascular risk score (2011 version). This instrument is used to calculate risk of CVD events in adults from 30 to 84 with no history of CVD or statin use.
Among 557 patients with a calculable QRISK2 score at 2 years of follow-up, there were four CVD events, including two cases of ischemic heart disease, one ischemic stroke, and one intracranial hemorrhage. The median 2-year QRISK2 score was 1.7%, and the 10-year risk was 9.0%, which translated in to an expected 9.5 CVD events during 2 years of follow-up.
Among the additional 104 patients who could not have a QRISK2 score calculated because of age over 84, statin use, or history of CVD, there were four CVD events: ischemic heart disease, transient ischemic attack/carotid artery stenosis, myocardial infarction, and intracranial hemorrhage.
Other CVD events occurring in both groups included atrial fibrillation in eight patients, other arrhythmia in three, and, in one patient each, aortic valve pathology, pericarditis, and carotid artery plaque.
Portuguese experience
Dr, Delgado and colleagues noted that although hemophilia has traditionally been regarded as protective against ischemic heart disease or thrombotic events, modern management “has prolonged life expectancy of people with hemophilia and consequently, an associated increase in incidence and prevalence of conditions that affect the general older population, such as cardiovascular disease and hypertension, are expected.”
They conducted a retrospective analysis of 100 adults (69 with hemophilia A, and 31 with hemophilia B) treated at their center. Overall, 29 patients had severe hemophilia A, 20 moderate hemophilia A, and 20 mild hemophilia A. Among patients with hemophilia B, 11 had severe, 15 moderate, and 5 mild disease.
Two patients (one with moderate and one with severe hemophilia) had angina episodes with coronary artery disease and underwent multiple coronary bypass grafts. The patient with severe disease had a disabling ischemic stroke during recovery from bypass surgery, and the patient with moderate hemophilia had an acute myocardial infarction prior to bypass surgery.
Two other patients had transient ischemic strokes from which they recovered without disability.
The main cardiovascular risk factors identified in this population were hypertension, diabetes mellitus, heavy smoking, obesity, and dyslipidemia. All patients were screened for prothrombotic risk, and all patients had negative test results.
“Hemophilia does not seem to have a protective effect against thrombotic/cardiovascular events, mainly in [patients with] coronary artery disease,” the investigators wrote.
Endothelial function
In a study presented in an oral abstract session, Shannon Jackson, MD, of the University of British Columbia in Vancouver found that men with hemophilia appear to have better macrovascular endothelial function but worse microvascular endothelial function than did men with normal clotting parameters.
“Based on endothelial function, contemporary hemophilia cohorts may have a different profile of cardiovascular risk than healthy controls,” she said.
Although they do not have an obvious mechanistic explanation for the differences in microvascular function among patients with hemophilia vs. healthy controls, there is evidence to show that microvascular function is predictive of cardiovascular events independent of other risk factors in otherwise healthy people. Their findings indicate that further study of the association between endothelial function, cardiovascular risk factors, and atherosclerosis among patients with hemophilia is warranted, she said.
Dr. van der Valk and colleagues and Dr. Delgado and colleagues did not disclose funding or conflicts of interest. The study by Dr. Jackson and colleagues was supported by the Canadian Hemophilia Society and Pfizer. She disclosed honoraria for speaking engagements for Biogen, Baxalta, and Pfizer and for participating in scientific advisory boards for Bayer, Pfizer, Baxalta, CLS Behring, and Novo Nordisk.
At WFH 2016 World Congress
Key clinical point: Hemophilia has traditionally been considered protective against CVD but data presented at the World Federation of Hemophilia World Congress show conflicting results.Major finding: The CVD event rate in one study was lower than predicted by risk scores, but a separate study showed a higher rate of events. A third study suggests that men with hemophilia have worse microvascular endothelial function than men without bleeding disorders.
Data source: Two prospective and one retrospective study of CVD in patients with hemophilia.
Disclosures: Dr. van der Valk and colleagues and Dr. Delgado and colleagues did not disclose funding or conflicts of interest. The study by Dr. Jackson and colleagues was supported by the Canadian Hemophilia Society and Pfizer. She disclosed honoraria for speaking engagements for Biogen, Baxalta, and Pfizer and for participating in scientific advisory boards for Bayer, Pfizer, Baxalta, CLS Behring, and Novo Nordisk.
Age, not infusion frequency, affects hemophilia prophylaxis adherence
ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.
A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.
“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.
Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).
Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.
“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.
The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).
Age may be a factor
In a separate study, German investigators report that adherence appears to vary by age.
Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.
Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.
“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.
Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.
Both studies were internally funded. The authors reported no relevant disclosures.
ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.
A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.
“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.
Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).
Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.
“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.
The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).
Age may be a factor
In a separate study, German investigators report that adherence appears to vary by age.
Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.
Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.
“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.
Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.
Both studies were internally funded. The authors reported no relevant disclosures.
ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.
A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.
“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.
Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).
Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.
“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.
The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).
Age may be a factor
In a separate study, German investigators report that adherence appears to vary by age.
Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.
Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.
“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.
Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.
Both studies were internally funded. The authors reported no relevant disclosures.
AT WFH 2016 WORLD CONGRESS
Key clinical point: Adherence to hemophilia prophylaxis regimens may be influenced by age but not frequency of infusions.
Major finding: Infusion frequency did not make a difference in adherence rates, but young and middle-aged adults reported lower adherence than did children or seniors.
Data source: A study of 23 pediatric hemophilia patients in Canada, and a separate study of 364 children and adults with moderate to severe hemophilia in Germany.
Disclosures: Both studies were internally funded. The authors reported no relevant disclosures.
Gene profile predicts RCC response to nivolumab
Many patients with advanced renal cell carcinoma have tumors that do not respond to immune checkpoint inhibitors targeted against the programmed death-1 (PD-1) pathway, despite expression of the target PD ligand 1 (PD-L1) on their tumors. Now investigators think they know why, and hope to use the information to predict which patients are likely to benefit and identify potential new therapies or combinations.
A study of renal cell carcinoma (RCC) samples from tumors with both good and poor clinical responses to treatment with the anti–PD-1 agent nivolumab (Opdivo) showed that a tumor gene–expression profile tipped more toward genes for controlling metabolic functions rather than immune functions was associated with a lack of response to anti-PD-1 therapy, reported Suzanne L. Topalian, MD, and her colleagues from Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, both in Baltimore.
“These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti–PD-1,” they wrote in a study published online in Cancer Immunology Research.
The investigators obtained tumor samples from 13 patients with unresectable metastatic RCC treated in one of four clinical trials. They used radiographic staging to classify each patient as either a responder or nonresponder to anti–PD-1 therapy according to RECIST (Response Evaluation Criteria in Solid Tumors). The samples were evaluated with whole genome microarray and multiplex quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling and analysis, and the results were compared with those from eight renal cell carcinoma cell lines.
They looked for expression of nearly 30,000 gene targets in samples from responders and nonresponders and found a pattern of differential expression of genes encoding for metabolic pathways and immune functions.
Specifically, they found that the expression of genes involved in metabolic and solute transport functions (for example, UGT1A) were associated with poor response to nivolumab, whereas overexpression of genes for immune markers involved in T-cell differentiation (BACH2) and leukocyte migration (CCL3) were associated with a good response.
The investigators acknowledge that the study was retrospective and limited by the analysis of only a small number of tumor samples but suggest that their findings point the way to further investigations in larger groups of patients with RCC tumors, including those both positive and negative for PD-L1 expression.
“The general approach to identifying biomarkers of clinical response to PD-1–targeted therapies has so far focused on immunologic factors in the [tumor microenvironment]. However, a deeper level of investigation may be warranted for individual tumor types, and intersections of tumor cell–intrinsic factors with immunologic factors may be particularly revealing,” they wrote.
The study was supported by research grants from the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Bristol-Myers Squibb, the National Cancer Institute, and Stand Up To Cancer. Dr. Topalian has served as a consultant/advisory board member for Five Prime Therapeutics, MedImmune, Merck, and Pfizer, and has an ownership interest in Bristol-Myers Squibb, Five Prime Therapeutics,and Potenza Therapeutics. Other coauthors reported similar potential conflicts of interest.
Many patients with advanced renal cell carcinoma have tumors that do not respond to immune checkpoint inhibitors targeted against the programmed death-1 (PD-1) pathway, despite expression of the target PD ligand 1 (PD-L1) on their tumors. Now investigators think they know why, and hope to use the information to predict which patients are likely to benefit and identify potential new therapies or combinations.
A study of renal cell carcinoma (RCC) samples from tumors with both good and poor clinical responses to treatment with the anti–PD-1 agent nivolumab (Opdivo) showed that a tumor gene–expression profile tipped more toward genes for controlling metabolic functions rather than immune functions was associated with a lack of response to anti-PD-1 therapy, reported Suzanne L. Topalian, MD, and her colleagues from Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, both in Baltimore.
“These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti–PD-1,” they wrote in a study published online in Cancer Immunology Research.
The investigators obtained tumor samples from 13 patients with unresectable metastatic RCC treated in one of four clinical trials. They used radiographic staging to classify each patient as either a responder or nonresponder to anti–PD-1 therapy according to RECIST (Response Evaluation Criteria in Solid Tumors). The samples were evaluated with whole genome microarray and multiplex quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling and analysis, and the results were compared with those from eight renal cell carcinoma cell lines.
They looked for expression of nearly 30,000 gene targets in samples from responders and nonresponders and found a pattern of differential expression of genes encoding for metabolic pathways and immune functions.
Specifically, they found that the expression of genes involved in metabolic and solute transport functions (for example, UGT1A) were associated with poor response to nivolumab, whereas overexpression of genes for immune markers involved in T-cell differentiation (BACH2) and leukocyte migration (CCL3) were associated with a good response.
The investigators acknowledge that the study was retrospective and limited by the analysis of only a small number of tumor samples but suggest that their findings point the way to further investigations in larger groups of patients with RCC tumors, including those both positive and negative for PD-L1 expression.
“The general approach to identifying biomarkers of clinical response to PD-1–targeted therapies has so far focused on immunologic factors in the [tumor microenvironment]. However, a deeper level of investigation may be warranted for individual tumor types, and intersections of tumor cell–intrinsic factors with immunologic factors may be particularly revealing,” they wrote.
The study was supported by research grants from the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Bristol-Myers Squibb, the National Cancer Institute, and Stand Up To Cancer. Dr. Topalian has served as a consultant/advisory board member for Five Prime Therapeutics, MedImmune, Merck, and Pfizer, and has an ownership interest in Bristol-Myers Squibb, Five Prime Therapeutics,and Potenza Therapeutics. Other coauthors reported similar potential conflicts of interest.
Many patients with advanced renal cell carcinoma have tumors that do not respond to immune checkpoint inhibitors targeted against the programmed death-1 (PD-1) pathway, despite expression of the target PD ligand 1 (PD-L1) on their tumors. Now investigators think they know why, and hope to use the information to predict which patients are likely to benefit and identify potential new therapies or combinations.
A study of renal cell carcinoma (RCC) samples from tumors with both good and poor clinical responses to treatment with the anti–PD-1 agent nivolumab (Opdivo) showed that a tumor gene–expression profile tipped more toward genes for controlling metabolic functions rather than immune functions was associated with a lack of response to anti-PD-1 therapy, reported Suzanne L. Topalian, MD, and her colleagues from Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, both in Baltimore.
“These findings suggest that tumor cell–intrinsic metabolic factors may contribute to treatment resistance in RCC, thus serving as predictive markers for treatment outcomes and potential new targets for combination therapy regimens with anti–PD-1,” they wrote in a study published online in Cancer Immunology Research.
The investigators obtained tumor samples from 13 patients with unresectable metastatic RCC treated in one of four clinical trials. They used radiographic staging to classify each patient as either a responder or nonresponder to anti–PD-1 therapy according to RECIST (Response Evaluation Criteria in Solid Tumors). The samples were evaluated with whole genome microarray and multiplex quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling and analysis, and the results were compared with those from eight renal cell carcinoma cell lines.
They looked for expression of nearly 30,000 gene targets in samples from responders and nonresponders and found a pattern of differential expression of genes encoding for metabolic pathways and immune functions.
Specifically, they found that the expression of genes involved in metabolic and solute transport functions (for example, UGT1A) were associated with poor response to nivolumab, whereas overexpression of genes for immune markers involved in T-cell differentiation (BACH2) and leukocyte migration (CCL3) were associated with a good response.
The investigators acknowledge that the study was retrospective and limited by the analysis of only a small number of tumor samples but suggest that their findings point the way to further investigations in larger groups of patients with RCC tumors, including those both positive and negative for PD-L1 expression.
“The general approach to identifying biomarkers of clinical response to PD-1–targeted therapies has so far focused on immunologic factors in the [tumor microenvironment]. However, a deeper level of investigation may be warranted for individual tumor types, and intersections of tumor cell–intrinsic factors with immunologic factors may be particularly revealing,” they wrote.
The study was supported by research grants from the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Bristol-Myers Squibb, the National Cancer Institute, and Stand Up To Cancer. Dr. Topalian has served as a consultant/advisory board member for Five Prime Therapeutics, MedImmune, Merck, and Pfizer, and has an ownership interest in Bristol-Myers Squibb, Five Prime Therapeutics,and Potenza Therapeutics. Other coauthors reported similar potential conflicts of interest.
FROM CANCER IMMUNOLOGY RESEARCH
Key clinical point: Many renal cell carcinoma tumors do not respond to therapy with an anti-PD-1 agent, despite being positive for the PD-L1 target.
Major finding: A gene expression profile favoring genes associated with metabolic and solute transport functions was associated with poor response to nivolumab.
Data source: Retrospective study of tumor gene expression in 13 patients with advanced RCC and 8 RCC cell lines.
Disclosures: The study was supported by research grants from the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore; Bristol-Myers Squibb; the National Cancer Institute; and Stand Up To Cancer. Dr. Topalian has served as a consultant/advisory board member for Five Prime Therapeutics, MedImmune, Merck, and Pfizer, and has an ownership interest in Bristol-Myers Squibb, Five Prime Therapeutics,and Potenza Therapeutics. Other coauthors reported similar potential conflicts of interest.
Post-AMI Death Risk Model Has High Predictive Accuracy
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Post-AMI death risk model has high predictive accuracy
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
Data analyses for the risk models developed by the ACTION Registry generally showed good accuracy and precision. The calibration information showed that patients with a cardiac arrest experienced much greater risk for mortality than did the other major groups (STEMI, NSTEMI, or no cardiac arrest). Until now, clinicians and researchers have generally used either the TIMI [Thrombolysis in Myocardial Infarction] or GRACE [Global Registry of Acute Coronary Events] score to guide therapeutic decisions. With the advent of the ACTION score, which appears to be most helpful for patients with moderate to severe disease, and the HEART [history, ECG, age, risk factor, troponin] score, which targets care for patients with minimal to mild disease, there are other options. Recently, the DAPT (Dual Antiplatelet Therapy) investigators published a prediction algorithm that provides yet another prognostic score to assess risk of ischemic events and risk of bleeding in patients who have undergone percutaneous coronary intervention. The key variables in the DAPT score are age, cigarette smoking, diabetes, MI at presentation, previous percutaneous coronary intervention or previous MI, use of a paclitaxel-eluting stent, stent diameter of less than 3 mm, heart failure or reduced ejection fraction, and use of a vein graft stent.
A comprehensive cross validation and comparison across at least some of the algorithms – TIMI, GRACE, HEART, DAPT, and ACTION – would help at this point. Interventions and decision points have evolved over the past 15 years, and evaluation of relatively contemporary data would be especially helpful. For example, the HEART score is likely to be used in situations in which the negative predictive capabilities are most important. The ACTION score is likely to be most useful in severely ill patients and to provide guidance for newer interventions. If detailed information concerning stents is available, then the DAPT score should prove helpful.
It is likely that one score does not fit all. Each algorithm provides a useful summary of risk to help guide decision making for patients with ischemic symptoms, depending on the severity of the signs and symptoms at presentation and the duration of the follow-up interval. Consensus building would help to move this field forward for hospital-based management of patients evaluated for cardiac ischemia.
Peter W.F. Wilson, MD, of the Atlanta VAMC and Emory Clinical Cardiovascular Research
Institute, Atlanta; and Ralph B. D’Agostino Sr., PhD, of the department of mathematics and statistics, Boston University, made these comments in an accompanying editorial (J Am Coll Cardiol. 2016 Aug 1;68[6]:636-8). They reported no relevant disclosures.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
An updated risk model based on data from patients presenting after acute myocardial infarction to a broad spectrum of U.S. hospitals appears to predict with a high degree of accuracy which patients are at the greatest risk for in-hospital mortality, investigators say.
Created from data on more than 240,000 patients presenting to one of 655 U.S. hospitals in 2012 and 2013 following ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation MI (NSTEMI), the model identified the following independent risk factors for in-hospital mortality: age, heart rate, systolic blood pressure, presentation to the hospital after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with STEMI, creatinine clearance, and troponin ratio, reported Robert L. McNamara, MD, of Yale University, New Haven, Conn.
The investigators are participants in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With the Guidelines).
“The new ACTION Registry–GWTG in-hospital mortality risk model and risk score represent robust, parsimonious, and contemporary risk adjustment methodology for use in routine clinical care and hospital quality assessment. The addition of risk adjustment for patients presenting after cardiac arrest is critically important and enables a fairer assessment across hospitals with varied case mix,” they wrote (J Am Coll Cardiol. 2016 Aug 1;68[6]:626-35).
The revised risk model has the potential to facilitate hospital quality assessments and help investigators to identify specific factors that could help clinicians even further lower death rates, the investigators write.
Further mortality reductions?
Although improvements in care of patients with acute MI over the last several decades have driven the in-hospital death rate from 29% in 1969 down to less than 7% today, there are still more than 100,000 AMI-related in-hospital deaths in the United States annually, with wide variations across hospitals, Dr. McNamara and colleagues noted.
A previous risk model published by ACTION Registry–GWTG members included data on patients treated at 306 U.S. hospitals and provided a simple, validated in-hospital mortality and risk score.
Since that model was published, however, the dataset was expanded to include patients presenting after cardiac arrest at the time of AMI presentation.
“Being able to adjust for cardiac arrest is critical because it is a well-documented predictor of mortality. Moreover, continued improvement in AMI care mandates periodic updates to the risk models so that hospitals can assess their quality as contemporary care continues to evolve,” the authors wrote.
To see whether they could develop a new and improved model and risk score, they analyzed data on 243,440 patients treated at one of 655 hospitals in the voluntary network. Data on 145,952 patients (60% of the total), 57,039 of whom presented with STEMI, and 88,913 of whom presented with NSTEMI, were used to for the derivation sample.
Data on the remaining 97,488 (38,060 with STEMI and 59,428 with NSTEMI) were used to create the validation sample.
The authors found that for the total cohort, the in-hospital mortality rate was 4.6%. In multivariate models controlled for demographic and clinical factors, independent risk factors significantly associated with in-hospital mortality (validation cohort) were:
• Presentation after cardiac arrest (odds ratio, 5.15).
• Presentation in cardiogenic shock (OR, 4.22).
• Presentation in heart failure (OR, 1.83).
• STEMI on electrocardiography (OR, 1.81).
• Age, per 5 years (OR, 1.24).
• Systolic BP, per 10 mm Hg decrease (OR, 1.19).
• Creatinine clearance per 5/mL/min/1.73 m2 decrease (OR, 1.11).
• Heart rate per 10 beats/min (OR, 1.09).
• Troponin ratio, per 5 units (OR, 1.05).
The 95% confidence intervals for all of the above factors were significant.
The C-statistic, a standard measure of the predictive accuracy of a logistic regression model, was 0.88, indicating that the final ACTION Registry–GWTG in-hospital mortality model had a high level of discrimination in both the derivation and validation populations, the authors state.
The ACTION Registry–GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: An updated cardiac mortality risk model may help to further reduce in-hospital deaths following acute myocardial infarction.
Major finding: The C-statistic for the model, a measure of predictive accuracy, was 0.88.
Data source: Updated risk model and in-hospital mortality score based on data from 243,440 patients following an AMI in 655 U.S. hospitals.
Disclosures: The ACTION Registry-GWTG is a Program of the American College of Cardiology and the American Heart Association, with funding from Schering-Plough and the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Dr. McNamara serves on a clinical trials endpoint adjudication committee for Pfizer. Other coauthors reported multiple financial relationships with pharmaceutical and medical device companies.
Children under 6 with factor XIII deficiency had no major bleeds with recombinant product
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
ORLANDO –A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency, a rare and serious bleeding disorder.
In a small international phase III trial, there were no major bleeding episodes among six young children treated for at least 1 year with recombinant factor XIII (rFXIII; trade name Tretten), reported Susan L. Kearney, MD, of Children’s Hospitals and Clinics of Minnesota in Minneapolis.
“Prophylaxis was effective. The annualized bleeding rate was zero and the mean trough [FXIII activity] was greater than 10%,” she said at a moderated poster session at the World Federation of Hemophilia World Congress. “We feel that recombinant factor XIII is safe and effective in pediatric subjects less than 6 years of age with congenital factor XIII-A subunit deficiency, similar to the older age cohort.”
Factor XIII-A subunit deficiency is a rare and serious heritable bleeding disorder associated with spontaneous intracranial hemorrhage and other unpredictable types of serious bleeding.
In a previous phase III trial, 77 patients, ranging in age from 7 to 60 years, received rFXIII for bleeding prophylaxis. When given monthly, the recombinant factor was effective at preventing serious bleeding in 90% of patients. The most commonly reported adverse events were headache, pain in the extremities, and injection site pain.
Based on these results, the Food and Drug Administration granted rFXIII orphan-drug designation for treatment of patients 6 and older with factor XIII-A subunit deficiency.
In the trial reported here, investigators from the United States, United Kingdom, Israel, and Denmark enrolled three boys and three girls under age 6 who had previously completed a single dose efficacy and safety study of rFXIII. The patients received intravenous rFXIII at a dose of 35 IU/kg every 28 days for a minimum of 52 weeks.
The total treatment duration ranged from 1.8 to 3.5 years, for a total of 16.6 patient years.
There were no thromboembolic events or systemic allergic reactions, the primary safety endpoint of the study. One patient experienced three incidences of atopic dermatitis, however; two serious adverse events related to head injuries from falls during play occurred in one patient, who did not experience intracranial hemorrhage.
Two adverse events were deemed to be probably or possibly related to rFXIII: a case of viral gastroenteritis affected one patient who recovered without a change in dose, and mild fluctuating lymphocytopenia seen at baseline persisted in another patient throughout the trial.
There were no inhibitory or noninhibitory antibodies to rFXIII detected in any patient during the trial, and there were no bleeding episodes requiring additional treatment. The 14 minor bleeding episodes seen in five patients did not require treatment with an FXIII-containing product, the authors noted.
“It’s a very rare disorder, but ... the phenotype is quite severe and patients are severely affected. So this product is very useful,” said Lakshmi Srivaths, MD, a pediatric hematologist at Texas Children’s Hospital in Houston. She was not involved in the study. Unlike patients with hemophilia A or B, who require frequent factor infusions, the long half-life of this product means patients need just once-a-month infusions “that change the phenotype very significantly.”
Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
AT WFH 2016 WORLD CONGRESS
Key clinical point: A recombinant form of factor XIII was effective at preventing serious bleeding episodes in young children with factor XIII-A subunit deficiency.
Major finding: No bleeds occurred within a year in children with factor XIII-A subunit deficiency.
Data source: Open-label international phase III trial in three boys and three girls under age 6.
Disclosures: Dr. Kearney disclosed grant/research support from Novo Nordisk, which funded the study. Some coauthors reported consulting or employment with the company.
Hemophilia guideline recommends integrated care model
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
ORLANDO – An integrated care model that includes a hematologist, a specialized hematology nurse, a physical therapist, a social worker, and 24/7 access to a specialized coagulation laboratory is recommended in a new hemophilia care guideline jointly developed by the National Hemophilia Foundation and McMaster University in Hamilton, Ontario.
The guideline has been formally accepted for inclusion in the National Guideline Clearinghouse (NGC), the National Hemophilia Foundation announced at its annual meeting, held immediately before the World Hemophilia Foundation World Congress here.
“The integrated care model, as is utilized within the U.S. federally funded network of hemophilia treatment centers (HTCs), should be advocated for optimal care of persons with hemophilia,” wrote guideline coauthors Steven W. Pipe, MD, from the University of Michigan School of Medicine in Ann Arbor, and Craig M. Kessler, MD, from Georgetown University in Washington, in an introduction to the guideline, published in the journal Hemophilia.
Developed according to evidence-based principles, the guideline is hoped to “promote harmonization of care delivery and reduce practice variations within the U.S. HTC network. This guideline will inform the HTC network how best to prioritize additional ‘high-value’ research to fill data gaps or strengthen the evidence base as outlined in the manuscript,” they added.
The guideline authors recognized three basic models of care in use in the United States:
The integrated care, comprehensive care, or HTC model, which generally assumes that all aspects of care will be delivered in a specialized center.
Specialist-based care, under which a hematologist may or may not have training in the management of patients with hemophilia, is provided in a hospital or medical office, but not in a specialized center.
Non-specialist care, delivered in an emergency department or primary care practitioners office.
“We believe that the ‘No Care’ model, theoretically indicating complete absence of care, does not currently operate in the U.S. Yet, this is likely the de facto model of care for many individuals with hemophilia who do not have access to care due to profound resource constraints, particularly in developing countries or underserved minorities,” the authors wrote.
The guideline’s main recommendation – that the integrated-care model is preferable to the non-integrated care model – is conditional, with moderate certainty in the evidence.
For persons with hemophilia with inhibitors to clotting factors, however, the integrated-care model recommendation is considered to be strong, with moderate certainty.
The guideline development panel found that there were significant gaps in evidence for the benefits of integrated care for specific populations such as older patients and populations with poor access to care, and called for additional studies to clarify these questions.
Additionally, the panelists call for study into which specific interventions or aspects of care should be included in the integrated model, and for more in-depth studies into the effects on patient-important outcomes.
“This collaborative project constitutes an important milestone on a critical component of evidence-based guideline methodology,” Alfonso Iorio, MD, PhD, from the Department of Clinical Epidemiology and Biostatistics at McMaster University, said in a press statement. “It demonstrates how a patient advocacy organization can promote and support a guideline process, in the true spirit of patient involvement in research and care process, without compromising a rigorous and transparent conflict of interest management process.”
The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
AT WFH 2016 WORLD CONGRESS
Key clinical point: An integrated care model is recommended as optimal for management of persons with hemophilia.
Major finding: The joint National Hemophilia Foundation/McMaster University guidelines have been accepted by the National Guideline Clearinghouse.
Data source: Evidence-based recommendations on models of care.
Disclosures: The guidelines were funded by the National Hemophilia Foundation. Several guideline panelists reported financial relationships with companies that make clotting factors and other products for persons with hemophilia.
Ipilimumab may restore antitumor immunity after relapse from HSCT
Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.
Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.
“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).
More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.
“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.
Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.
The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.
Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.
There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.
Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.
The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.
Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).
The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.
The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.
Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.
Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.
“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).
More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.
“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.
Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.
The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.
Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.
There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.
Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.
The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.
Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).
The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.
The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.
Early data hint that immune checkpoint inhibitors may be able to restore antitumor activity in patients with hematologic malignancies that have relapsed after allogeneic transplant.
Among 22 patients with relapsed hematologic cancers following allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/Ib study, treatment with the anti-CTLA-4 antibody ipilimumab (Yervoy) at a dose of 10 mg/kg was associated with complete responses in five patients, partial responses in two, and decreased tumor burden in six, reported Matthew S. Davids, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues.
“CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, even in patients with refractory myeloid cancers,” they wrote (N Engl J Med. 2016 Jul 14. doi: 10.1056/NEJMoa1601202).
More than one-third of patients who undergo HSCT for hematologic malignancies such as lymphoma, multiple myeloma, or leukemia will experience a relapse, and most will die within a year of relapse despite salvage therapies or retransplantation, the authors noted.
“Immune escape (i.e., tumor evasion of the donor immune system) contributes to relapse after allogeneic HSCT, and immune checkpoint inhibitory pathways probably play an important role,” they wrote.
Selective CTLA-4 blockade has been shown in mouse models to treat late relapse after transplantation by augmenting graft-versus-tumor response without apparent exacerbation of graft-versus-host disease (GVHD). To see whether the use of a CTLA-4 inhibitor could have the same effect in humans, the investigators instituted a single-group, open-label, dose-finding, safety and efficacy study of ipilimumab in 28 patients from six treatment sites.
The patients had all undergone allogeneic HSCT more than 3 months before the start of the study. The diagnoses included acute myeloid leukemia (AML) in 12 patients (including 3 with leukemia cutis and 1 with a myeloid sarcoma), Hodgkin lymphoma in 7, non-Hodgkin lymphoma in 4, myelodysplastic syndrome (MDS) in 2, and multiple myeloma, myeloproliferative neoplasm, and acute lymphoblastic leukemia in 1 patient each. Eight of the patients had previously had either grade I or II acute GVHD; 16 had had chronic GVHD.
Patients received induction therapy with ipilimumab at a dose of either 3 mg/kg (6 patients), or 10 mg/kg (22 patients) every 3 weeks for a total of 4 doses. Patients who experienced a clinical benefit from the drug could receive additional doses every 12 weeks for up to 60 weeks.
There were no clinical responses meeting study criteria in any of the patients who received the 3-mg/kg dose. Among the 22 who received the 10-mg/kg dose, however, the rate of complete responses was 23% (5 of 22), partial responses 9% (2 of 22), and decreased tumor burden 27% (6 of 22). The remaining nine patients experienced disease progression.
Four of the complete responses occurred in patients with extramedullary AML, and one occurred in a patient with MDS transforming into AML.
The safety analysis, which included all 28 patients evaluable for adverse events, showed four discontinuations due to dose-limiting chronic GVHD of the liver in the 3 patients, and acute GVHD of the gut in 1, and to severe immune-related events in one additional patient, leading to the patient’s death.
Other grade 3 or greater adverse events possibly related to ipilimumab included acute kidney injury (one patient) , corneal ulcer (one), thrombocytopenia (nine), neutropenia (three), anemia and pleural effusion (two).
The investigators point out that therapy to stimulate a graft-versus-tumor effect has the potential to promote or exacerbate GVHD, as occurred in four patients in the study. The GVHD in these patients was effectively managed with glucocorticoids, however.
The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Anti-CTLA-4 therapy may restore graft-versus-tumor effect in patients with hematologic malignancies relapsed after allogeneic transplantation.
Major finding: Five of 22 patients on a 10-mg/kg dose of ipilimumab had a complete response.
Data source: Phase I/Ib investigator-initiated study of 28 patients with hematologic malignancies relapsed after allogeneic hematopoietic stem cell transplantation.
Disclosures: The National Institutes of Health, Leukemia and Lymphoma Society, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute supported the study. Dr. Davids disclosed grants from ASCO, the Pasquarello Tissue Bank, NIH, NCI, and Leukemia and Lymphoma society, and personal fees from several companies outside the study. Several coauthors disclosed relationships with various pharmaceutical companies, including Bristol-Myers Squibb, maker of ipilimumab.
