Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.
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.)
James
W Philip T
WP
London School of Hygiene and Tropical Medicine, London, England. jeanhjames@aol.com
Caterson
Ian D
ID
Coutinho
Walmir
W
Finer
Nick
N
Van Gaal
Luc F
LF
Maggioni
Aldo P
AP
Torp-Pedersen
Christian
C
Sharma
Arya M
AM
Shepherd
Gillian M
GM
Rode
Richard A
RA
Renz
Cheryl L
CL
D000368:Aged; D001067:Appetite Depressants / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology* / Q000401:mortality; D003503:Cyclobutanes / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D009765:Obesity / Q000150:complications / Q000188:drug therapy*; D050177:Overweight / Q000150:complications / Q000188:drug therapy*; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology
D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine