Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects
W Philip T James1, Ian D Caterson, Walmir Coutinho
1London School of Hygiene and Tropical Medicine, London, England. jeanhjames@aol.com
Insights
Long-term sibutramine treatment in high-risk patients increased the risk of heart attack and stroke, but not cardiovascular death. Weight management with sibutramine requires careful consideration of these cardiovascular risks.
Area of Science:
- Cardiology
- Pharmacology
- Obesity Medicine
Background:
- Long-term cardiovascular effects of sibutramine remain unestablished in high-risk populations.
- Sibutramine is a weight-management drug with potential cardiovascular implications.
Purpose of the Study:
- To assess cardiovascular consequences of weight management with and without sibutramine.
- To evaluate the long-term effects of sibutramine on cardiovascular events and death in high-risk individuals.
Main Methods:
- 10,744 overweight/obese subjects (≥55 years) with pre-existing cardiovascular disease or type 2 diabetes were studied.
- A 6-week lead-in period with sibutramine and weight management was followed by double-blind randomization to sibutramine or placebo.
- Primary endpoint: time to first major adverse cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, cardiac arrest resuscitation, or cardiovascular death).
Main Results:
- Over a mean of 3.4 years, sibutramine group had a higher risk of primary outcome events (11.4% vs. 10.0%, HR 1.16, P=0.02).
- Increased rates of nonfatal myocardial infarction (HR 1.28, P=0.02) and nonfatal stroke (HR 1.36, P=0.03) were observed in the sibutramine group.
- No significant increase in cardiovascular death or all-cause mortality was found.
Conclusions:
- Long-term sibutramine treatment in patients with pre-existing cardiovascular conditions increases nonfatal myocardial infarction and stroke risk.
- Sibutramine did not increase cardiovascular or all-cause mortality in this high-risk cohort.
- These findings highlight the need for careful risk-benefit assessment when prescribing sibutramine for weight management.
Background:
The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established.
Methods:
We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death).
Results:
The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased.
Conclusions:
Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)
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