Mary Ann Moon

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Adding omalizumab to guideline-based asthma treatment decreased symptoms, exacerbations, hospitalizations, and the need for glucocorticoids in children, adolescents, and young adults living in the inner city, according to a report in the March 17 issue of the New England Journal of Medicine.

The monoclonal anti-IgE antibody was particularly effective in patients who were allergic to cockroach and dust allergens. Moreover, "a striking additional post hoc finding was the marked reduction in seasonal exacerbations seen with omalizumab," said Dr. William W. Busse of the University of Wisconsin, Madison, and his associates.

"Our purpose in designing this study was to examine whether specifically targeting the allergic component in persistent asthma would offer a benefit beyond that provided by conventional treatment for asthma control, regardless of disease severity," they noted.

The investigators compared subcutaneous injections of omalizumab vs. placebo injections in a multicenter clinical trial involving 419 children, adolescents, and young adults (aged 6-20 years) who had persistent allergic asthma. After 1 month on guideline-based treatment, the study subjects were randomly assigned to additionally receive active (208 subjects) or placebo (211 subjects) injections every 2 weeks or 4 weeks, for a total of 60 weeks.

At baseline, the average number of days during the preceding 2 weeks in which participants had asthma symptoms was 4.9, and 25% of patients had been hospitalized at least once during the preceding year for an asthma-related event. The average age of the study subjects was 11 years. In all, 58% were male; 60% were black, and 37% were Hispanic.

The primary outcome (defined as the number of symptomatic days during the preceding 2 weeks) was decreased to 0.48 days with omalizumab, compared with 1.48 days with placebo, a significant 25% reduction. Exacerbations occurred in 49% of the placebo group, compared with 30% of the omalizumab group, which was also a significant difference. And the rate of asthma-related hospitalizations also was significantly lower with omalizumab (1.5%) than with placebo (6.3%).

Patients who took omalizumab were able to significantly reduce their use of inhaled glucocorticoids, with an overall budesonide-equivalent dose of 663 mcg/day, compared with 771 mcg/day with placebo.

These benefits "were similar in patients of all ages and at all levels of asthma severity," and were first observed within 4 weeks of beginning the injections, Dr. Busse and his colleagues said (N. Engl. J. Med. 2011;364:1005-15).

"No differences of concern regarding safety were noted between the two groups," they added.

The greatest treatment effect was seen in participants who were sensitized to cockroach allergen and were known to be exposed to it, based on environmental sampling from their bedrooms. These subjects showed a 71% reduction in asthma exacerbations. Subjects who were allergic to dust mites also showed greater reductions in days with symptoms and the use of glucocorticoids, compared with those who were not sensitized to dust mites.

"Even though we found omalizumab effective at all levels of asthma severity, we do not advocate its use outside of current recommendations given its cost and remaining questions regarding long-term safety in children. We do, however, believe that this study provides a strong proof of concept that the allergic component of asthma is crucial in this population," the investigators said.

"This postulate is further supported by our finding that omalizumab’s benefit was greatest in participants who were both sensitized and exposed to cockroach allergen and in those sensitized to dust mites, two major indoor allergens," they added.

In a post hoc analysis, the researchers found that omalizumab also markedly reduced seasonal exacerbations of asthma. "Viral respiratory infections are a major cause of exacerbations, especially in the fall, with the start of school, but they were identified in less than 60% of the samples available for analysis, suggesting that other factors, such as allergen exposure, pollution, stress, or bacteria, also contribute to the risk of exacerbation.

"Omalizumab was equally effective in reducing exacerbations in the fall and the spring, with or without a viral infection, but it did not appear to prevent viral respiratory infections," Dr. Busse and his associates said.

These findings imply that targeting the drug to patients who are sensitized to cockroach and dust mite allergens, as well as focusing its use on preventing seasonal peaks in asthma exacerbations, would yield the optimal effectiveness and cost benefit, they added.

This study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and Novartis Pharmaceuticals. Dey Pharma provided EpiPens and S.C. Johnson provided household pest control products. Dr. Busse and his associates reported ties to numerous drug and device manufacturers.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Among older white men, CHD risk is approximately twice as high in those who developed type 2 diabetes relatively early in adulthood and have had the disease for more than 8 years, compared with those who developed it later and have had it for fewer than 8 years, according to a report in the March 14 issue of Archives of Internal Medicine.

In older white men with an earlier onset and a longer duration of type 2 diabetes, the risk of CHD events is equivalent to that of nondiabetic men who had already had prior myocardial infarction, said S. Goya Wannamethee, Ph.D., of the department of primary care and population health, University College London, and associates.

"Although diabetes is a well-established risk factor for CHD, whether diabetes alone is a CHD equivalent in assessing the risk of future cardiovascular events [has been] controversial. ... Our observations plus prior research [suggest] that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond 8 years," they noted.

Dr. Wannamethee and colleagues examined the relationship among age of diabetes onset, duration of disease, and cardiovascular risk using data from the British Regional Heart Study (BRHS), a prospective assessment of cardiovascular disease in 7,735 white men aged 40-59 years at enrollment in 1978-1980 who were recruited from general practices in 24 British towns. For this analysis, data were assessed on 4,045 of these subjects who were 60-79 years of age at the 20-year mark of the BRHS and were followed for all-cause mortality and CVD morbidity for a mean of 9 more years.

During that time there were 372 major CHD events, including 263 CHD deaths.

Men with an early onset of type 2 diabetes, with a diagnosis at or before age 60, had a mean duration of disease of 16.7 years. Their CHD risk was approximately twice that of men who had a later onset, with a diagnosis after age 60 and a mean duration of disease of 4.9 years.

"Moreover, the [relative risk] for vascular events and mortality in [men] with early onset of diabetes were comparable to those in men with prior MI, suggesting that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent," the investigators said (Arch. Intern. Med. 2011;171:404-10).

These findings should go a long way toward resolving the confusion and debate over the issue, and explain why previous studies that did not specifically address age of onset or disease duration have yielded conflicting results, they noted.

"The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher. This pattern ... emphasizes the need to be aggressive with CHD risk reduction [that is, statin use and blood pressure modification] in patients with type 2 diabetes diagnosed at a relatively young age," Dr. Wannamethee and associates said.

"Finally, neither adjustment for traditional risk factors nor a range of novel risk factors (including markers of inflammation, endothelial dysfunction, and renal dysfunction) explained the excess CHD risk in patients with known diabetes, particularly in those with early onset. These men still showed an almost threefold increase in risk after adjustment," compared with men who did not have diabetes.

Future studies of this issue must examine whether the findings hold true in women and people of nonwhite ethnicities, they added.

The British Regional Heart Study is supported by the British Heart Foundation. No financial conflicts of interest were reported.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

Patients who quit smoking shortly before undergoing surgery are not at increased risk of postoperative complications, compared with those who continue to smoke, according to a report published online March 14 in the Archives of Internal Medicine.

"Until some new evidence of harm emerges, firm advice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time," said Katie Myers of Queen Mary, University of London, and her associates.

Publication of a study in 1989 with 39 subjects suggested that "stopping smoking leads to a decrease in coughing and an increase in sputum production." Although that article did not actually show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery "to minimize the increase in pulmonary complications in recent quitters."

Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as "high quality" the three studies that also used biochemical testing to validate subjects’ self-report of their smoking status.

These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.

Only one of the nine studies showed a significant effect of smoking cessation, and that was in favor of recent quitting. When the results were pooled, there was "no beneficial or detrimental effect of quitting within 8 weeks before surgery, compared with continued smoking," the researchers said.

The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications.

"In conclusion, there is currently no suggestion, either from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications," the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archinternmed.2011.97]).

The reluctance to allow or encourage smoking cessation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has directly examined mucociliary clearance in surgical patients shortly after smoking cessation, and that study found no significant difference between surgical patients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

"No data are available on the effects of only a few days’ abstinence from smoking. Early abstinence generates more intense withdrawal discomfort, but there is no clear rationale to expect this to translate into postoperative complications," they added.

However, they acknowledged that their study is limited by its observational nature and by the small number of studies available for review that have evaluated this issue. "Our findings are necessarily tentative and may be modified when more data become available," the researchers said.

One of Ms. Myers’ associates is supported by the U.K. Center for Tobacco Control Studies. Two associates reported ties to GlaxoSmithKline, Novartis, Pfizer Global, and Johnson & Johnson, which manufacture smoking cessation products.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.