In Reply: I thank Dr. Keller for his interest in my review on the side effects and drug interactions of proton pump inhibitors (PPIs).¹ In particular, the concern about the potentially increased risk of a cardiovascular event in patients taking a PPI while on clopidogrel is a matter of active research. Since the prevention of death, myocardial infarction, or stroke is the desired outcome in patients receiving antiplatelet therapy, any reduction in the antiplatelet effect of clopidogrel could put patients at increased risk. Because of the enormous number of patients on both PPIs and clopidogrel, investigators are studying the effect of PPIs on clopidogrel to determine the true significance in day-to-day practice. We should expect that the data will continue to evolve in the coming years as more research is done on this important interaction.

The FDA Web site that Dr. Keller brings up² was posted a few months after the submission of my manuscript. But even with the FDA’s cautionary words, it is important to realize that the risk that purportedly exists with the interaction of omeprazole and clopidogrel and the suggestion for the alternative use of pantoprazole are both based on pharmacokinetic, pharmacodynamic, and epidemiologic studies, not on clinical outcome data.

As much as we would like to rely on such studies, pharmacokinetic and pharmacodynamic studies do not address clinical outcomes, and observational studies cannot account for every confounder, because patients in these studies are not randomly assigned to the intervention, which is the rationale behind the necessity for a prospective trial. The Clopidogrel and the Optimization of Gastrointestinal Events (COGENT) study,³ a prospective randomized controlled trial with 3,761 analyzed patients, found no differences in adjudicated cardiovascular outcomes between groups who received a clopidogrel plus omeprazole vs clopidogrel alone.³ Although the COGENT study ended prematurely because of bankruptcy of the funding source, these outcomes represent the only randomized prospective data that can be found to date on PubMed. With such large numbers of patients in each group (1,876 and 1,885, respectively) and no differences in outcomes, it stands to reason that only a study with massive sample sizes would be able to detect a statistically significant difference. Differences between clopidogrel-treated patients taking and not taking omeprazole are likely be found in a well-designed prospective trial; however, it would be virtually impossible to find differences among PPIs.

To make matters even less convincing that therapy should be altered, the Working Group on High On-treatment Platelet Reactivity stated in their recent consensus paper that there are “limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes.” ⁴ Additionally, a recent multisociety Expert Consensus Document discussing the concomitant use of PPIs and thienopyridine drugs to reduce gastrointestinal complications further supports this argument.⁵ Therefore, it is difficult to justify a marked increase in cost of the PPI selected (pantoprazole costs nearly seven times more per dose than omeprazole, according to one Web site⁶) for a benefit that is supported only by theoretical and observational data, not by outcome data.

As Dr. Keller also mentions, Aggrenox can be used for secondary stroke prophylaxis, but a discussion about a therapeutic exchange between clopidogrel and other antiplatelet agents was beyond the scope of my review. A recently published joint guideline of the American Heart Association and the American Stroke Association guideline should be consulted for further information.⁷

Other gastroprotective therapies are available. However, misoprostol (as mentioned) is associated with significant gastrointestinal side effects and must be taken four times a day. H2-receptor antagonists are not considered to be as effective as PPIs.^8,9

In Reply: I thank Dr. Keller for his interest in my review on the side effects and drug interactions of proton pump inhibitors (PPIs).¹ In particular, the concern about the potentially increased risk of a cardiovascular event in patients taking a PPI while on clopidogrel is a matter of active research. Since the prevention of death, myocardial infarction, or stroke is the desired outcome in patients receiving antiplatelet therapy, any reduction in the antiplatelet effect of clopidogrel could put patients at increased risk. Because of the enormous number of patients on both PPIs and clopidogrel, investigators are studying the effect of PPIs on clopidogrel to determine the true significance in day-to-day practice. We should expect that the data will continue to evolve in the coming years as more research is done on this important interaction.

The FDA Web site that Dr. Keller brings up² was posted a few months after the submission of my manuscript. But even with the FDA’s cautionary words, it is important to realize that the risk that purportedly exists with the interaction of omeprazole and clopidogrel and the suggestion for the alternative use of pantoprazole are both based on pharmacokinetic, pharmacodynamic, and epidemiologic studies, not on clinical outcome data.

As much as we would like to rely on such studies, pharmacokinetic and pharmacodynamic studies do not address clinical outcomes, and observational studies cannot account for every confounder, because patients in these studies are not randomly assigned to the intervention, which is the rationale behind the necessity for a prospective trial. The Clopidogrel and the Optimization of Gastrointestinal Events (COGENT) study,³ a prospective randomized controlled trial with 3,761 analyzed patients, found no differences in adjudicated cardiovascular outcomes between groups who received a clopidogrel plus omeprazole vs clopidogrel alone.³ Although the COGENT study ended prematurely because of bankruptcy of the funding source, these outcomes represent the only randomized prospective data that can be found to date on PubMed. With such large numbers of patients in each group (1,876 and 1,885, respectively) and no differences in outcomes, it stands to reason that only a study with massive sample sizes would be able to detect a statistically significant difference. Differences between clopidogrel-treated patients taking and not taking omeprazole are likely be found in a well-designed prospective trial; however, it would be virtually impossible to find differences among PPIs.

To make matters even less convincing that therapy should be altered, the Working Group on High On-treatment Platelet Reactivity stated in their recent consensus paper that there are “limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes.” ⁴ Additionally, a recent multisociety Expert Consensus Document discussing the concomitant use of PPIs and thienopyridine drugs to reduce gastrointestinal complications further supports this argument.⁵ Therefore, it is difficult to justify a marked increase in cost of the PPI selected (pantoprazole costs nearly seven times more per dose than omeprazole, according to one Web site⁶) for a benefit that is supported only by theoretical and observational data, not by outcome data.

As Dr. Keller also mentions, Aggrenox can be used for secondary stroke prophylaxis, but a discussion about a therapeutic exchange between clopidogrel and other antiplatelet agents was beyond the scope of my review. A recently published joint guideline of the American Heart Association and the American Stroke Association guideline should be consulted for further information.⁷

Other gastroprotective therapies are available. However, misoprostol (as mentioned) is associated with significant gastrointestinal side effects and must be taken four times a day. H2-receptor antagonists are not considered to be as effective as PPIs.^8,9

In Reply: I thank Dr. Keller for his interest in my review on the side effects and drug interactions of proton pump inhibitors (PPIs).¹ In particular, the concern about the potentially increased risk of a cardiovascular event in patients taking a PPI while on clopidogrel is a matter of active research. Since the prevention of death, myocardial infarction, or stroke is the desired outcome in patients receiving antiplatelet therapy, any reduction in the antiplatelet effect of clopidogrel could put patients at increased risk. Because of the enormous number of patients on both PPIs and clopidogrel, investigators are studying the effect of PPIs on clopidogrel to determine the true significance in day-to-day practice. We should expect that the data will continue to evolve in the coming years as more research is done on this important interaction.

The FDA Web site that Dr. Keller brings up² was posted a few months after the submission of my manuscript. But even with the FDA’s cautionary words, it is important to realize that the risk that purportedly exists with the interaction of omeprazole and clopidogrel and the suggestion for the alternative use of pantoprazole are both based on pharmacokinetic, pharmacodynamic, and epidemiologic studies, not on clinical outcome data.

As much as we would like to rely on such studies, pharmacokinetic and pharmacodynamic studies do not address clinical outcomes, and observational studies cannot account for every confounder, because patients in these studies are not randomly assigned to the intervention, which is the rationale behind the necessity for a prospective trial. The Clopidogrel and the Optimization of Gastrointestinal Events (COGENT) study,³ a prospective randomized controlled trial with 3,761 analyzed patients, found no differences in adjudicated cardiovascular outcomes between groups who received a clopidogrel plus omeprazole vs clopidogrel alone.³ Although the COGENT study ended prematurely because of bankruptcy of the funding source, these outcomes represent the only randomized prospective data that can be found to date on PubMed. With such large numbers of patients in each group (1,876 and 1,885, respectively) and no differences in outcomes, it stands to reason that only a study with massive sample sizes would be able to detect a statistically significant difference. Differences between clopidogrel-treated patients taking and not taking omeprazole are likely be found in a well-designed prospective trial; however, it would be virtually impossible to find differences among PPIs.

To make matters even less convincing that therapy should be altered, the Working Group on High On-treatment Platelet Reactivity stated in their recent consensus paper that there are “limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes.” ⁴ Additionally, a recent multisociety Expert Consensus Document discussing the concomitant use of PPIs and thienopyridine drugs to reduce gastrointestinal complications further supports this argument.⁵ Therefore, it is difficult to justify a marked increase in cost of the PPI selected (pantoprazole costs nearly seven times more per dose than omeprazole, according to one Web site⁶) for a benefit that is supported only by theoretical and observational data, not by outcome data.

As Dr. Keller also mentions, Aggrenox can be used for secondary stroke prophylaxis, but a discussion about a therapeutic exchange between clopidogrel and other antiplatelet agents was beyond the scope of my review. A recently published joint guideline of the American Heart Association and the American Stroke Association guideline should be consulted for further information.⁷

Other gastroprotective therapies are available. However, misoprostol (as mentioned) is associated with significant gastrointestinal side effects and must be taken four times a day. H2-receptor antagonists are not considered to be as effective as PPIs.^8,9

To the Editor: Thank you for the excellent review on proton pump inhibitors (PPIs) in the January 2011 issue.¹ I would like to make the following comments about Dr. Madanick’s suggested algorithm (see Figure 2 in the article) for deciding whether to use a PPI in patients requiring clopidogrel:

A posting dated October 27, 2010, on the Web site of the US Food and Drug Administration (FDA) states the following: “With regard to the proton pump inhibitor (PPI) drug class, this recommendation [against the concomitant use of Plavix (clopidogrel) and omeprazole (Prilosec)] applies only to omeprazole and not to all PPIs. Not all PPIs have the same inhibitory effect on the enzyme [CYP2C19] that is crucial for conversion of Plavix into its active form. Pantoprazole (Protonix) may be an alternative PPI for consideration. It is a weak inhibitor of CYP2C19 and has less effect on the pharmacological activity of Plavix than omeprazole.”² Thus, when it is deemed necessary to coadminister clopidogrel with a PPI, pantoprazole appears to be the preferred PPI.

If the patient is taking clopidogrel for stroke prophylaxis, one can consider switching to Aggrenox (aspirin plus extended-release dipyridamole), which has no warnings regarding coadministration with PPIs.

Patients taking aspirin plus clopidogrel may benefit by the addition of misoprostol (Cytotec), which is indicated for reducing the risk of aspirin-induced gastric ulcers in patients at high risk of complications from gastric ulcer.

To the Editor: Thank you for the excellent review on proton pump inhibitors (PPIs) in the January 2011 issue.¹ I would like to make the following comments about Dr. Madanick’s suggested algorithm (see Figure 2 in the article) for deciding whether to use a PPI in patients requiring clopidogrel:

A posting dated October 27, 2010, on the Web site of the US Food and Drug Administration (FDA) states the following: “With regard to the proton pump inhibitor (PPI) drug class, this recommendation [against the concomitant use of Plavix (clopidogrel) and omeprazole (Prilosec)] applies only to omeprazole and not to all PPIs. Not all PPIs have the same inhibitory effect on the enzyme [CYP2C19] that is crucial for conversion of Plavix into its active form. Pantoprazole (Protonix) may be an alternative PPI for consideration. It is a weak inhibitor of CYP2C19 and has less effect on the pharmacological activity of Plavix than omeprazole.”² Thus, when it is deemed necessary to coadminister clopidogrel with a PPI, pantoprazole appears to be the preferred PPI.

If the patient is taking clopidogrel for stroke prophylaxis, one can consider switching to Aggrenox (aspirin plus extended-release dipyridamole), which has no warnings regarding coadministration with PPIs.

Patients taking aspirin plus clopidogrel may benefit by the addition of misoprostol (Cytotec), which is indicated for reducing the risk of aspirin-induced gastric ulcers in patients at high risk of complications from gastric ulcer.

To the Editor: Thank you for the excellent review on proton pump inhibitors (PPIs) in the January 2011 issue.¹ I would like to make the following comments about Dr. Madanick’s suggested algorithm (see Figure 2 in the article) for deciding whether to use a PPI in patients requiring clopidogrel:

A posting dated October 27, 2010, on the Web site of the US Food and Drug Administration (FDA) states the following: “With regard to the proton pump inhibitor (PPI) drug class, this recommendation [against the concomitant use of Plavix (clopidogrel) and omeprazole (Prilosec)] applies only to omeprazole and not to all PPIs. Not all PPIs have the same inhibitory effect on the enzyme [CYP2C19] that is crucial for conversion of Plavix into its active form. Pantoprazole (Protonix) may be an alternative PPI for consideration. It is a weak inhibitor of CYP2C19 and has less effect on the pharmacological activity of Plavix than omeprazole.”² Thus, when it is deemed necessary to coadminister clopidogrel with a PPI, pantoprazole appears to be the preferred PPI.

If the patient is taking clopidogrel for stroke prophylaxis, one can consider switching to Aggrenox (aspirin plus extended-release dipyridamole), which has no warnings regarding coadministration with PPIs.

Patients taking aspirin plus clopidogrel may benefit by the addition of misoprostol (Cytotec), which is indicated for reducing the risk of aspirin-induced gastric ulcers in patients at high risk of complications from gastric ulcer.

As we strive to provide the most advanced care possible to our patients with vascular disease, there is one area of our practice that stands out as being as archaic as cellophane wrapping of aneurysms: the process of finding a job.

Instead of an enlightening quest to find the perfect practice, many graduating vascular fellows have found it to be a tiring and laborious process. The excitement around the opportunity to finally do what we have trained so long and hard to do has been eclipsed in frustration by a disorganized and antiquated interview process.

The business side of medicine has very much been on display in the popular media with the institution of new healthcare reform legislation. No financially viable business would fly a client halfway across the country to find out if they're a 'good guy' prior to discussing a potential deal. This should not be the routine in medicine, either.

I implore vascular surgeons to utilize technology to modernize the process of expanding their practice. Replace the 'good old boy' and device rep networks with posts on the Society for Vascular Surgery (SVS) Job bank. Loose the recruiters and write a concise description of your current practice and what you have to offer. Replace the mandatory meet and greet first interview with a video conference via SKYPE. This will obviate the need to clear your schedule for the day and shelve the awkward interview in the operating theater.

A colleague of mine has equated interviewing for a vascular surgery job with trying to buy a used car without knowing the price. Even if it requires a non-disclosure agreement, opening the books to a prospective partner early in the interview process is vital. In addition to demonstrating integrity and building good will, it validates your case mix and volume. Without this knowledge, an applicant cannot make an informed decision to join a practice.

Most importantly, be professional. If a candidate is not what you're looking for, be straightforward and tactful. Communicate; don't string someone along in case another prospect falls through.

For those of you who are getting ready to or are still looking for your first job- do your homework. Converse with your faculty members, get in touch with the local device reps, and talk to former fellows about your job prospects. On the interview don't hesitate to pull the ancillary staff aside for their opinion of the group. One of my co-fellows did this and learned that the surgeon had not booked a case in the operating room for six months. The hospital administrators confessed that they were interviewing to replace the surgeon, not hire on a partner.

There are a multitude of resources available to arm yourself when it comes to contract negotiations. Read "The Physician's Comprehensive Guide to Negotiating" (SEAK, Inc.) by Steven Babitsky and James J. Mangraviti, Jr. I obtained a copy through interlibrary loan and read it in two days between cases. It is well worth the small time investment.
Call your institution's physician contract liaison to review a sample contract and gain access to the MGMA physician salary survey. Remember these data includes responses from vascular surgeons in both private practice and academics and may not reflect your true market value. Talk to the fellows who graduated before you to get an idea of what range of offers are out there.

Attend regional and national vascular surgery conferences to network and gain leads. The SVS young surgeon's forum at the annual meeting is a good introduction into the job search process. The most comprehensive review to date is the Mote Vascular Symposium put on by Dr. Russell H. Samson's group out of Sarasota, FL. Beg, borrow, or steal the weekend off to attend this meeting.

Our goal as graduating fellows is to not only provide exceptional care to the patients with vascular disease in the communities we join, but to modernize the practice of our partners. Whether this means an aggressive endovascular approach to aneurysmal disease or overseeing the redesign of the practice's website, by virtue of training in the information age we are well prepared.

Every page of this newspaper is geared toward making us better vascular surgeons. So please, let's start by bringing the interview process in to the 21st century.

Christopher Everett, M.D., is a Vascular Surgery Fellow, year two, at the Greenville University Hospital Medical Center, Greenville, SC.

As we strive to provide the most advanced care possible to our patients with vascular disease, there is one area of our practice that stands out as being as archaic as cellophane wrapping of aneurysms: the process of finding a job.

Instead of an enlightening quest to find the perfect practice, many graduating vascular fellows have found it to be a tiring and laborious process. The excitement around the opportunity to finally do what we have trained so long and hard to do has been eclipsed in frustration by a disorganized and antiquated interview process.

The business side of medicine has very much been on display in the popular media with the institution of new healthcare reform legislation. No financially viable business would fly a client halfway across the country to find out if they're a 'good guy' prior to discussing a potential deal. This should not be the routine in medicine, either.

I implore vascular surgeons to utilize technology to modernize the process of expanding their practice. Replace the 'good old boy' and device rep networks with posts on the Society for Vascular Surgery (SVS) Job bank. Loose the recruiters and write a concise description of your current practice and what you have to offer. Replace the mandatory meet and greet first interview with a video conference via SKYPE. This will obviate the need to clear your schedule for the day and shelve the awkward interview in the operating theater.

A colleague of mine has equated interviewing for a vascular surgery job with trying to buy a used car without knowing the price. Even if it requires a non-disclosure agreement, opening the books to a prospective partner early in the interview process is vital. In addition to demonstrating integrity and building good will, it validates your case mix and volume. Without this knowledge, an applicant cannot make an informed decision to join a practice.

Most importantly, be professional. If a candidate is not what you're looking for, be straightforward and tactful. Communicate; don't string someone along in case another prospect falls through.

For those of you who are getting ready to or are still looking for your first job- do your homework. Converse with your faculty members, get in touch with the local device reps, and talk to former fellows about your job prospects. On the interview don't hesitate to pull the ancillary staff aside for their opinion of the group. One of my co-fellows did this and learned that the surgeon had not booked a case in the operating room for six months. The hospital administrators confessed that they were interviewing to replace the surgeon, not hire on a partner.

There are a multitude of resources available to arm yourself when it comes to contract negotiations. Read "The Physician's Comprehensive Guide to Negotiating" (SEAK, Inc.) by Steven Babitsky and James J. Mangraviti, Jr. I obtained a copy through interlibrary loan and read it in two days between cases. It is well worth the small time investment.
Call your institution's physician contract liaison to review a sample contract and gain access to the MGMA physician salary survey. Remember these data includes responses from vascular surgeons in both private practice and academics and may not reflect your true market value. Talk to the fellows who graduated before you to get an idea of what range of offers are out there.

Attend regional and national vascular surgery conferences to network and gain leads. The SVS young surgeon's forum at the annual meeting is a good introduction into the job search process. The most comprehensive review to date is the Mote Vascular Symposium put on by Dr. Russell H. Samson's group out of Sarasota, FL. Beg, borrow, or steal the weekend off to attend this meeting.

Our goal as graduating fellows is to not only provide exceptional care to the patients with vascular disease in the communities we join, but to modernize the practice of our partners. Whether this means an aggressive endovascular approach to aneurysmal disease or overseeing the redesign of the practice's website, by virtue of training in the information age we are well prepared.

Every page of this newspaper is geared toward making us better vascular surgeons. So please, let's start by bringing the interview process in to the 21st century.

Christopher Everett, M.D., is a Vascular Surgery Fellow, year two, at the Greenville University Hospital Medical Center, Greenville, SC.

As we strive to provide the most advanced care possible to our patients with vascular disease, there is one area of our practice that stands out as being as archaic as cellophane wrapping of aneurysms: the process of finding a job.

Instead of an enlightening quest to find the perfect practice, many graduating vascular fellows have found it to be a tiring and laborious process. The excitement around the opportunity to finally do what we have trained so long and hard to do has been eclipsed in frustration by a disorganized and antiquated interview process.

The business side of medicine has very much been on display in the popular media with the institution of new healthcare reform legislation. No financially viable business would fly a client halfway across the country to find out if they're a 'good guy' prior to discussing a potential deal. This should not be the routine in medicine, either.

I implore vascular surgeons to utilize technology to modernize the process of expanding their practice. Replace the 'good old boy' and device rep networks with posts on the Society for Vascular Surgery (SVS) Job bank. Loose the recruiters and write a concise description of your current practice and what you have to offer. Replace the mandatory meet and greet first interview with a video conference via SKYPE. This will obviate the need to clear your schedule for the day and shelve the awkward interview in the operating theater.

A colleague of mine has equated interviewing for a vascular surgery job with trying to buy a used car without knowing the price. Even if it requires a non-disclosure agreement, opening the books to a prospective partner early in the interview process is vital. In addition to demonstrating integrity and building good will, it validates your case mix and volume. Without this knowledge, an applicant cannot make an informed decision to join a practice.

Most importantly, be professional. If a candidate is not what you're looking for, be straightforward and tactful. Communicate; don't string someone along in case another prospect falls through.

For those of you who are getting ready to or are still looking for your first job- do your homework. Converse with your faculty members, get in touch with the local device reps, and talk to former fellows about your job prospects. On the interview don't hesitate to pull the ancillary staff aside for their opinion of the group. One of my co-fellows did this and learned that the surgeon had not booked a case in the operating room for six months. The hospital administrators confessed that they were interviewing to replace the surgeon, not hire on a partner.

There are a multitude of resources available to arm yourself when it comes to contract negotiations. Read "The Physician's Comprehensive Guide to Negotiating" (SEAK, Inc.) by Steven Babitsky and James J. Mangraviti, Jr. I obtained a copy through interlibrary loan and read it in two days between cases. It is well worth the small time investment.
Call your institution's physician contract liaison to review a sample contract and gain access to the MGMA physician salary survey. Remember these data includes responses from vascular surgeons in both private practice and academics and may not reflect your true market value. Talk to the fellows who graduated before you to get an idea of what range of offers are out there.

Attend regional and national vascular surgery conferences to network and gain leads. The SVS young surgeon's forum at the annual meeting is a good introduction into the job search process. The most comprehensive review to date is the Mote Vascular Symposium put on by Dr. Russell H. Samson's group out of Sarasota, FL. Beg, borrow, or steal the weekend off to attend this meeting.

Our goal as graduating fellows is to not only provide exceptional care to the patients with vascular disease in the communities we join, but to modernize the practice of our partners. Whether this means an aggressive endovascular approach to aneurysmal disease or overseeing the redesign of the practice's website, by virtue of training in the information age we are well prepared.

Every page of this newspaper is geared toward making us better vascular surgeons. So please, let's start by bringing the interview process in to the 21st century.

Christopher Everett, M.D., is a Vascular Surgery Fellow, year two, at the Greenville University Hospital Medical Center, Greenville, SC.

With this issue, we begin a new column which we have chosen to call Residents' Forum. We hope that Vascular Residents, Fellows, and others interested in entering this exciting field will consider submitting an essay on topics important to them related to vascular surgery and their careers.

-George Andros, M.D., Medical Editor

With this issue, we begin a new column which we have chosen to call Residents' Forum. We hope that Vascular Residents, Fellows, and others interested in entering this exciting field will consider submitting an essay on topics important to them related to vascular surgery and their careers.

-George Andros, M.D., Medical Editor

With this issue, we begin a new column which we have chosen to call Residents' Forum. We hope that Vascular Residents, Fellows, and others interested in entering this exciting field will consider submitting an essay on topics important to them related to vascular surgery and their careers.

-George Andros, M.D., Medical Editor

LAKE BUENA VISTA, FLA. - Endovascular treatment for critical limb ischemia offered no significant cost savings over open repair in a recent analysis of outcomes in 137 patients.

Of the 148 patients included in the retrospective review, 42% were treated with an endovascular procedure, 47% with an open procedure, and the remaining with a hybrid of the two. The mean costs were $49,802 for an endovascular hospitalization and $45,832 for an open repair hospitalization; these amounts were not significantly different, Dr. Nicholas Gargiulo III reported at the annual meeting of the Society for Clinical Vascular Surgery.

The mean lengths of stay were also similar, at 9.3 days and 10.4 days in the endovascular and open repair groups, respectively, said Dr. Gargiulo of Montefiore Medical Center, New York.

The percentage of patients discharged to a skilled nursing facility was 35% vs. 44% of endovascular and open repair patients, respectively. Although endovascular repair was associated with slightly increased likelihood of recovering enough function to be released to home upon hospital discharge, this difference also did not reach statistical significance.

Rates of readmission within 90 days were similar at 12% and 13% for the endovascular repair and open repair patients, respectively.

For hybrid repair patients, the hospitalization costs ($27,922) and length of stay (9.8 days) were lower, compared with the other groups. However, the readmission rate was much higher, at 50%, and the percentage discharged to home initially was lower at 28%.

The study included all of those patients who presented with critical limb ischemia at Montefiore Medical Center from January 1, 2007, through December 2007, for whom complete data were available. The patients, who had a mean age of 67 years and Rutherford Class 4 or 5 disease, underwent initial diagnostic evaluation with conventional arteriography, and the treatment approach was based on the anatomic TransAtlantic InterSociety Consensus II classification and adequate runoff.

A variety of endovascular interventions and open procedures were used. The perioperative mortality rate was 2.7%, and amputation-free survival was 94.6% at 1 year.

Most of the patients had hypertension and diabetes; a large variety of other comorbidities were seen as well.

About two-thirds of the cohort presented with rest pain, and the remainder presented with gangrene or ulceration. The hospitalization costs were higher in those who presented with gangrene and ulceration, Dr. Gargiulo said. Over the past year, more patients have been presenting with gangrene than with rest pain, and this is a concern, he added.

“Interestingly, the only thing that was different is that those with rest pain cost less than the patients with gangrene and ulceration … gangrene and ulceration increase the length of stay, increase readmission, and of course increase supplies and nursing services, resulting in an overall increase in mean cost,” Dr. Gargiulo said.

Possible cost-cutting measures include educational programs, new alliances with podiatry colleagues, prevention, and new trials, he added.

“In conclusion, endovascular and open procedures were equally cost effective in this diverse ethnic population of patients with critical limb ischemia, and patients with gangrene and ulceration have increased health care costs. It appears it's not the type of procedure which incurs cost, but the clinical presentation,” he said.

Dr. Gargiulo had no disclosures.

LAKE BUENA VISTA, FLA. - Endovascular treatment for critical limb ischemia offered no significant cost savings over open repair in a recent analysis of outcomes in 137 patients.

Of the 148 patients included in the retrospective review, 42% were treated with an endovascular procedure, 47% with an open procedure, and the remaining with a hybrid of the two. The mean costs were $49,802 for an endovascular hospitalization and $45,832 for an open repair hospitalization; these amounts were not significantly different, Dr. Nicholas Gargiulo III reported at the annual meeting of the Society for Clinical Vascular Surgery.

The mean lengths of stay were also similar, at 9.3 days and 10.4 days in the endovascular and open repair groups, respectively, said Dr. Gargiulo of Montefiore Medical Center, New York.

The percentage of patients discharged to a skilled nursing facility was 35% vs. 44% of endovascular and open repair patients, respectively. Although endovascular repair was associated with slightly increased likelihood of recovering enough function to be released to home upon hospital discharge, this difference also did not reach statistical significance.

Rates of readmission within 90 days were similar at 12% and 13% for the endovascular repair and open repair patients, respectively.

For hybrid repair patients, the hospitalization costs ($27,922) and length of stay (9.8 days) were lower, compared with the other groups. However, the readmission rate was much higher, at 50%, and the percentage discharged to home initially was lower at 28%.

The study included all of those patients who presented with critical limb ischemia at Montefiore Medical Center from January 1, 2007, through December 2007, for whom complete data were available. The patients, who had a mean age of 67 years and Rutherford Class 4 or 5 disease, underwent initial diagnostic evaluation with conventional arteriography, and the treatment approach was based on the anatomic TransAtlantic InterSociety Consensus II classification and adequate runoff.

A variety of endovascular interventions and open procedures were used. The perioperative mortality rate was 2.7%, and amputation-free survival was 94.6% at 1 year.

Most of the patients had hypertension and diabetes; a large variety of other comorbidities were seen as well.

About two-thirds of the cohort presented with rest pain, and the remainder presented with gangrene or ulceration. The hospitalization costs were higher in those who presented with gangrene and ulceration, Dr. Gargiulo said. Over the past year, more patients have been presenting with gangrene than with rest pain, and this is a concern, he added.

“Interestingly, the only thing that was different is that those with rest pain cost less than the patients with gangrene and ulceration … gangrene and ulceration increase the length of stay, increase readmission, and of course increase supplies and nursing services, resulting in an overall increase in mean cost,” Dr. Gargiulo said.

Possible cost-cutting measures include educational programs, new alliances with podiatry colleagues, prevention, and new trials, he added.

“In conclusion, endovascular and open procedures were equally cost effective in this diverse ethnic population of patients with critical limb ischemia, and patients with gangrene and ulceration have increased health care costs. It appears it's not the type of procedure which incurs cost, but the clinical presentation,” he said.

Dr. Gargiulo had no disclosures.

LAKE BUENA VISTA, FLA. - Endovascular treatment for critical limb ischemia offered no significant cost savings over open repair in a recent analysis of outcomes in 137 patients.

Of the 148 patients included in the retrospective review, 42% were treated with an endovascular procedure, 47% with an open procedure, and the remaining with a hybrid of the two. The mean costs were $49,802 for an endovascular hospitalization and $45,832 for an open repair hospitalization; these amounts were not significantly different, Dr. Nicholas Gargiulo III reported at the annual meeting of the Society for Clinical Vascular Surgery.

The mean lengths of stay were also similar, at 9.3 days and 10.4 days in the endovascular and open repair groups, respectively, said Dr. Gargiulo of Montefiore Medical Center, New York.

The percentage of patients discharged to a skilled nursing facility was 35% vs. 44% of endovascular and open repair patients, respectively. Although endovascular repair was associated with slightly increased likelihood of recovering enough function to be released to home upon hospital discharge, this difference also did not reach statistical significance.

Rates of readmission within 90 days were similar at 12% and 13% for the endovascular repair and open repair patients, respectively.

For hybrid repair patients, the hospitalization costs ($27,922) and length of stay (9.8 days) were lower, compared with the other groups. However, the readmission rate was much higher, at 50%, and the percentage discharged to home initially was lower at 28%.

The study included all of those patients who presented with critical limb ischemia at Montefiore Medical Center from January 1, 2007, through December 2007, for whom complete data were available. The patients, who had a mean age of 67 years and Rutherford Class 4 or 5 disease, underwent initial diagnostic evaluation with conventional arteriography, and the treatment approach was based on the anatomic TransAtlantic InterSociety Consensus II classification and adequate runoff.

A variety of endovascular interventions and open procedures were used. The perioperative mortality rate was 2.7%, and amputation-free survival was 94.6% at 1 year.

Most of the patients had hypertension and diabetes; a large variety of other comorbidities were seen as well.

About two-thirds of the cohort presented with rest pain, and the remainder presented with gangrene or ulceration. The hospitalization costs were higher in those who presented with gangrene and ulceration, Dr. Gargiulo said. Over the past year, more patients have been presenting with gangrene than with rest pain, and this is a concern, he added.

“Interestingly, the only thing that was different is that those with rest pain cost less than the patients with gangrene and ulceration … gangrene and ulceration increase the length of stay, increase readmission, and of course increase supplies and nursing services, resulting in an overall increase in mean cost,” Dr. Gargiulo said.

Possible cost-cutting measures include educational programs, new alliances with podiatry colleagues, prevention, and new trials, he added.

“In conclusion, endovascular and open procedures were equally cost effective in this diverse ethnic population of patients with critical limb ischemia, and patients with gangrene and ulceration have increased health care costs. It appears it's not the type of procedure which incurs cost, but the clinical presentation,” he said.

Dr. Gargiulo had no disclosures.

SAN DIEGO - At 5 years of follow-up, patients who had ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation had equally good clinical results compared with patients who underwent surgical treatment of varicose veins, based on a randomized controlled trial.

"Since surgery may not provide a definitive treatment, foam sclerotherapy could be offered like a dental care treatment model: treating as and when the problem appears," Dr. Evi Kalodiki said at the annual meeting of the American Venous Forum.

Dr. Kalodiki, a vascular surgeon at Ealing Hospital and Imperial College, London, and her associates evaluated 82 legs that were treated in 73 patients. The mean age of the patients was 48 years, and 75% were female.

The researchers randomized the cases to two treatments: 39 legs underwent saphenofemoral ligation, stripping, and multiple phlebectomies under general anesthesia (surgery group) and 43 underwent saphenofemoral ligation under local anesthesia with concurrent foam sclerotherapy (foam group).

Assessments included ultrasound, the CEAP (clinical, etiologic, anatomical, pathophysiologic) classification, the Venous Clinical Severity Score, the Aberdeen Varicose Veins Questionnaire (AVVQ), and the Short Form-36 Health Survey (SF-36). Follow-ups were conducted annually to a median of 5.12 years.

Dr. Kalodiki reported that the CEAP classification was similar for the two groups, as was the percentage of legs that required additional foam sessions (40% of legs in the surgery group, with a mean volume of 11 mL for each case, vs. 48% of legs in the foam group, with a mean volume of 9 mL for each case.

Preoperative Venous Clinical Severity Scores (VCSS) were similar for the two groups (median of 5 in the surgery group vs. 4 in the foam group), as were post-treatment VCSS, at a median of 1 in each group.

Median changes in VCSS from baseline to 5 years were similar in the two groups: 3 in the surgery group vs. 3.5 in the foam group. Absolute VCSS values at 5 years were a median of 1 in each group.

The AVVQ score also improved in both groups. In the surgery group, the median AVVQ score improved from 16.32 preoperatively to 8.94 at 3 years, while in the foam group the median AVVQ score improved from 12.28 preoperatively to 4.97 at 3 years. These results were maintained at 5 years.

Scores on the mental component of the SF-36 worsened in the surgery group. There was no change in the physical scores of the SF-36 in either group over 3 or 5 years.

There were no significant differences between the groups or within the groups regarding obliteration or reflux above the knee or below the knee at 3 or 5 years. In the majority of cases, the reflux was asymptomatic and was only detected because of the follow-up duplex examination.

The study was funded by STD Pharmaceutical. Dr. Kalodiki said that she had no relevant financial disclosures.

SAN DIEGO - At 5 years of follow-up, patients who had ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation had equally good clinical results compared with patients who underwent surgical treatment of varicose veins, based on a randomized controlled trial.

"Since surgery may not provide a definitive treatment, foam sclerotherapy could be offered like a dental care treatment model: treating as and when the problem appears," Dr. Evi Kalodiki said at the annual meeting of the American Venous Forum.

Dr. Kalodiki, a vascular surgeon at Ealing Hospital and Imperial College, London, and her associates evaluated 82 legs that were treated in 73 patients. The mean age of the patients was 48 years, and 75% were female.

The researchers randomized the cases to two treatments: 39 legs underwent saphenofemoral ligation, stripping, and multiple phlebectomies under general anesthesia (surgery group) and 43 underwent saphenofemoral ligation under local anesthesia with concurrent foam sclerotherapy (foam group).

Assessments included ultrasound, the CEAP (clinical, etiologic, anatomical, pathophysiologic) classification, the Venous Clinical Severity Score, the Aberdeen Varicose Veins Questionnaire (AVVQ), and the Short Form-36 Health Survey (SF-36). Follow-ups were conducted annually to a median of 5.12 years.

Dr. Kalodiki reported that the CEAP classification was similar for the two groups, as was the percentage of legs that required additional foam sessions (40% of legs in the surgery group, with a mean volume of 11 mL for each case, vs. 48% of legs in the foam group, with a mean volume of 9 mL for each case.

Preoperative Venous Clinical Severity Scores (VCSS) were similar for the two groups (median of 5 in the surgery group vs. 4 in the foam group), as were post-treatment VCSS, at a median of 1 in each group.

Median changes in VCSS from baseline to 5 years were similar in the two groups: 3 in the surgery group vs. 3.5 in the foam group. Absolute VCSS values at 5 years were a median of 1 in each group.

The AVVQ score also improved in both groups. In the surgery group, the median AVVQ score improved from 16.32 preoperatively to 8.94 at 3 years, while in the foam group the median AVVQ score improved from 12.28 preoperatively to 4.97 at 3 years. These results were maintained at 5 years.

Scores on the mental component of the SF-36 worsened in the surgery group. There was no change in the physical scores of the SF-36 in either group over 3 or 5 years.

There were no significant differences between the groups or within the groups regarding obliteration or reflux above the knee or below the knee at 3 or 5 years. In the majority of cases, the reflux was asymptomatic and was only detected because of the follow-up duplex examination.

The study was funded by STD Pharmaceutical. Dr. Kalodiki said that she had no relevant financial disclosures.

SAN DIEGO - At 5 years of follow-up, patients who had ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation had equally good clinical results compared with patients who underwent surgical treatment of varicose veins, based on a randomized controlled trial.

"Since surgery may not provide a definitive treatment, foam sclerotherapy could be offered like a dental care treatment model: treating as and when the problem appears," Dr. Evi Kalodiki said at the annual meeting of the American Venous Forum.

Dr. Kalodiki, a vascular surgeon at Ealing Hospital and Imperial College, London, and her associates evaluated 82 legs that were treated in 73 patients. The mean age of the patients was 48 years, and 75% were female.

The researchers randomized the cases to two treatments: 39 legs underwent saphenofemoral ligation, stripping, and multiple phlebectomies under general anesthesia (surgery group) and 43 underwent saphenofemoral ligation under local anesthesia with concurrent foam sclerotherapy (foam group).

Assessments included ultrasound, the CEAP (clinical, etiologic, anatomical, pathophysiologic) classification, the Venous Clinical Severity Score, the Aberdeen Varicose Veins Questionnaire (AVVQ), and the Short Form-36 Health Survey (SF-36). Follow-ups were conducted annually to a median of 5.12 years.

Dr. Kalodiki reported that the CEAP classification was similar for the two groups, as was the percentage of legs that required additional foam sessions (40% of legs in the surgery group, with a mean volume of 11 mL for each case, vs. 48% of legs in the foam group, with a mean volume of 9 mL for each case.

Preoperative Venous Clinical Severity Scores (VCSS) were similar for the two groups (median of 5 in the surgery group vs. 4 in the foam group), as were post-treatment VCSS, at a median of 1 in each group.

Median changes in VCSS from baseline to 5 years were similar in the two groups: 3 in the surgery group vs. 3.5 in the foam group. Absolute VCSS values at 5 years were a median of 1 in each group.

The AVVQ score also improved in both groups. In the surgery group, the median AVVQ score improved from 16.32 preoperatively to 8.94 at 3 years, while in the foam group the median AVVQ score improved from 12.28 preoperatively to 4.97 at 3 years. These results were maintained at 5 years.

Scores on the mental component of the SF-36 worsened in the surgery group. There was no change in the physical scores of the SF-36 in either group over 3 or 5 years.

There were no significant differences between the groups or within the groups regarding obliteration or reflux above the knee or below the knee at 3 or 5 years. In the majority of cases, the reflux was asymptomatic and was only detected because of the follow-up duplex examination.

The study was funded by STD Pharmaceutical. Dr. Kalodiki said that she had no relevant financial disclosures.

SAN DIEGO - Patients with chronic venous disease who were treated surgically were significantly more likely to experience relief of symptoms than were those who underwent conservative therapy, results from a single-center study showed.

“The interventional treatment of varicose veins is considered to be medically necessary by insurance policies if the patient remains symptomatic after compression stockings or conservative therapy,” Dr. Fedor Lurie said at the annual meeting of the American Venous Forum. “This is despite the fact that little is known about symptoms of chronic venous disease. Even less known is how the symptoms of chronic venous disease react to treatment.”

Dr. Lurie and his colleague, Dr. Robert L. Kistner, prospectively studied 150 patients (59 men, 91 women; mean age 55 years) with CEAP class 2-4 primary chronic venous disease who were treated at the Kistner Vein Clinic in Honolulu during a 12-month period. (CEAP is a classification system based on the elements of Clinical severity, Etiology or cause, Anatomy, and Pathophysiology.) Initial treatment consisted of compression stockings and other conservative measures, after which patients chose whether to continue conservative treatment or undergo surgery.

Patients completed the Specific Quality of Life and Outcome Response-Venous (SQOR-V) assessment prior to the initial visit, after completion of conservative treatment, and at 1- and 12-month follow-up visits after surgical treatment. The quality of life and symptom score components of this tool were analyzed separately.

Following conservative treatment, symptom scores improved in 85 patients (57%), while quality of life scores improved in 111 patients (74%). Despite this improvement, 121 patients (81%) chose to undergo surgical treatment.

During the 1-month follow-up after surgical treatment, symptom scores improved in 97 patients (80%), while quality of life scores improved in 114 patients (94%).
Dr. Lurie also reported that 51 of 65 patients who did not improve after conservative treatment were treated surgically. Of those 51, only 30 (59%) improved after surgery.

Patients whose symptom scores improved after conservative treatment were 15.2 times more likely to have symptom relief at 1 month and 21.3 times more likely to have symptom relief at 1 year than were those who had no improvement in symptom scores. They were also 9.4 times more likely to have improved quality of life at 1 month and 4.3 times more likely to have improved quality of life at 1 year.

“The relief of symptoms by conservative therapy is a good predictor of successful surgical treatment,” said Dr. Lurie, who is also a clinical professor of vascular surgery at the University of Hawaii. “These findings contradict the present practice of insurance policies that interpret the success of conservative measures as a contraindication to surgical treatment, and provide evidence that those who respond favorably to conservative treatment are the ones who will benefit greatly from surgical elimination of the venous reflux.”

He concluded by noting that when the treatment goal is relief of symptoms, “success of conservative therapy should be considered an indication for surgical treatment, and the failure of conservative therapy should be an indication for reconsideration of the true cause of the symptoms.”

Dr. Lurie and Dr. Kistner said that they had no relevant financial disclosures.

SAN DIEGO - Patients with chronic venous disease who were treated surgically were significantly more likely to experience relief of symptoms than were those who underwent conservative therapy, results from a single-center study showed.

“The interventional treatment of varicose veins is considered to be medically necessary by insurance policies if the patient remains symptomatic after compression stockings or conservative therapy,” Dr. Fedor Lurie said at the annual meeting of the American Venous Forum. “This is despite the fact that little is known about symptoms of chronic venous disease. Even less known is how the symptoms of chronic venous disease react to treatment.”

Dr. Lurie and his colleague, Dr. Robert L. Kistner, prospectively studied 150 patients (59 men, 91 women; mean age 55 years) with CEAP class 2-4 primary chronic venous disease who were treated at the Kistner Vein Clinic in Honolulu during a 12-month period. (CEAP is a classification system based on the elements of Clinical severity, Etiology or cause, Anatomy, and Pathophysiology.) Initial treatment consisted of compression stockings and other conservative measures, after which patients chose whether to continue conservative treatment or undergo surgery.

Patients completed the Specific Quality of Life and Outcome Response-Venous (SQOR-V) assessment prior to the initial visit, after completion of conservative treatment, and at 1- and 12-month follow-up visits after surgical treatment. The quality of life and symptom score components of this tool were analyzed separately.

Following conservative treatment, symptom scores improved in 85 patients (57%), while quality of life scores improved in 111 patients (74%). Despite this improvement, 121 patients (81%) chose to undergo surgical treatment.

During the 1-month follow-up after surgical treatment, symptom scores improved in 97 patients (80%), while quality of life scores improved in 114 patients (94%).
Dr. Lurie also reported that 51 of 65 patients who did not improve after conservative treatment were treated surgically. Of those 51, only 30 (59%) improved after surgery.

Patients whose symptom scores improved after conservative treatment were 15.2 times more likely to have symptom relief at 1 month and 21.3 times more likely to have symptom relief at 1 year than were those who had no improvement in symptom scores. They were also 9.4 times more likely to have improved quality of life at 1 month and 4.3 times more likely to have improved quality of life at 1 year.

“The relief of symptoms by conservative therapy is a good predictor of successful surgical treatment,” said Dr. Lurie, who is also a clinical professor of vascular surgery at the University of Hawaii. “These findings contradict the present practice of insurance policies that interpret the success of conservative measures as a contraindication to surgical treatment, and provide evidence that those who respond favorably to conservative treatment are the ones who will benefit greatly from surgical elimination of the venous reflux.”

He concluded by noting that when the treatment goal is relief of symptoms, “success of conservative therapy should be considered an indication for surgical treatment, and the failure of conservative therapy should be an indication for reconsideration of the true cause of the symptoms.”

Dr. Lurie and Dr. Kistner said that they had no relevant financial disclosures.

SAN DIEGO - Patients with chronic venous disease who were treated surgically were significantly more likely to experience relief of symptoms than were those who underwent conservative therapy, results from a single-center study showed.

“The interventional treatment of varicose veins is considered to be medically necessary by insurance policies if the patient remains symptomatic after compression stockings or conservative therapy,” Dr. Fedor Lurie said at the annual meeting of the American Venous Forum. “This is despite the fact that little is known about symptoms of chronic venous disease. Even less known is how the symptoms of chronic venous disease react to treatment.”

Dr. Lurie and his colleague, Dr. Robert L. Kistner, prospectively studied 150 patients (59 men, 91 women; mean age 55 years) with CEAP class 2-4 primary chronic venous disease who were treated at the Kistner Vein Clinic in Honolulu during a 12-month period. (CEAP is a classification system based on the elements of Clinical severity, Etiology or cause, Anatomy, and Pathophysiology.) Initial treatment consisted of compression stockings and other conservative measures, after which patients chose whether to continue conservative treatment or undergo surgery.

Patients completed the Specific Quality of Life and Outcome Response-Venous (SQOR-V) assessment prior to the initial visit, after completion of conservative treatment, and at 1- and 12-month follow-up visits after surgical treatment. The quality of life and symptom score components of this tool were analyzed separately.

Following conservative treatment, symptom scores improved in 85 patients (57%), while quality of life scores improved in 111 patients (74%). Despite this improvement, 121 patients (81%) chose to undergo surgical treatment.

During the 1-month follow-up after surgical treatment, symptom scores improved in 97 patients (80%), while quality of life scores improved in 114 patients (94%).
Dr. Lurie also reported that 51 of 65 patients who did not improve after conservative treatment were treated surgically. Of those 51, only 30 (59%) improved after surgery.

Patients whose symptom scores improved after conservative treatment were 15.2 times more likely to have symptom relief at 1 month and 21.3 times more likely to have symptom relief at 1 year than were those who had no improvement in symptom scores. They were also 9.4 times more likely to have improved quality of life at 1 month and 4.3 times more likely to have improved quality of life at 1 year.

“The relief of symptoms by conservative therapy is a good predictor of successful surgical treatment,” said Dr. Lurie, who is also a clinical professor of vascular surgery at the University of Hawaii. “These findings contradict the present practice of insurance policies that interpret the success of conservative measures as a contraindication to surgical treatment, and provide evidence that those who respond favorably to conservative treatment are the ones who will benefit greatly from surgical elimination of the venous reflux.”

He concluded by noting that when the treatment goal is relief of symptoms, “success of conservative therapy should be considered an indication for surgical treatment, and the failure of conservative therapy should be an indication for reconsideration of the true cause of the symptoms.”

Dr. Lurie and Dr. Kistner said that they had no relevant financial disclosures.

CHICAGO - Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

“This was a definitively negative trial,” Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.
 
The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

“I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn't make therapeutic decisions based on phase II trials,” he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis “remains alive,” but the focus should shift to stem cell-based therapies, which show great promise.
 
Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It's possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn't changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.
 
Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO - Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

“This was a definitively negative trial,” Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.
 
The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

“I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn't make therapeutic decisions based on phase II trials,” he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis “remains alive,” but the focus should shift to stem cell-based therapies, which show great promise.
 
Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It's possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn't changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.
 
Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO - Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

“This was a definitively negative trial,” Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.
 
The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

“I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn't make therapeutic decisions based on phase II trials,” he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis “remains alive,” but the focus should shift to stem cell-based therapies, which show great promise.
 
Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It's possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn't changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.
 
Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.