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SCOUT: Sibutramine linked to MI, stroke risks
Curfman GD. N Engl J Med. 2010;363:972-974.
James WPT. N Engl J Med. 2010;363:905-917.
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People with pre-existing cardiovascular conditions who took long-term sibutramine for weight loss had an increased risk for nonfatal myocardial infarction and nonfatal stroke, according to the final results of SCOUT.
Participants who were assigned to sibutramine (Meridia, Abbott) for a mean 3.4 years had an 11.4% risk for a primary outcome event (nonfatal MI, nonfatal stroke, resuscitation after cardiac arrest or cardiovascular death) compared with a 10% risk among patients assigned to placebo (HR=1.16; 95% CI, 1.03-1.31). The weight-loss drug was also linked to a 4.1% rate of nonfatal MI vs. 3.2% with placebo (HR=1.28; 95% CI, 1.04-1.57), and a 2.6% vs. 1.9% rate of nonfatal stroke (HR=1.36; 95% CI, 1.04-1.77).
Sibutramine was not associated with CV death or death from any cause.
“On the basis of these results, sibutramine should continue to be excluded from use in patients with pre-existing CV disease,” W. Philip T. James, MD, DSc, of the London School of Hygiene and Tropical Medicine, and colleagues wrote in the New England Journal of Medicine.
Final SCOUT data
The Sibutramine Cardiovascular Outcomes Trial (SCOUT) included 10,744 overweight or obese adults aged 55 years and older. All participants in the randomized, double blind, placebo-controlled trial had pre-existing CVD, type 2 diabetes or both at baseline.
The researchers randomly assigned participants to sibutramine in addition to a weight-management program for 6 weeks during a single blind, lead-in period. After, 9,804 participants underwent randomization to sibutramine (n=4,906) or placebo (n=4,898).
During the 6-week lead-in period, participants lost a mean 2.6 g with sibutramine. After randomization, participants assigned to the drug achieved and maintained a further weight reduction of 1.7 kg.
In addition, mean blood pressure decreased in both the sibutramine and placebo groups, with greater reductions recorded in the placebo group vs. the sibutramine group (mean difference: 1.2/1.4 mm Hg).
Under fire again
Results of a preliminary analysis of the SCOUT trial indicated that participants who received sibutramine had a significantly higher incidence of major adverse CV events, which lead the FDA to require stronger language on the drug label. These new data now confirm the preliminary analysis findings.
After the preliminary SCOUT data were released, the European Medicines Agency suspended marketing of medications containing sibutramine in January 2010.
“Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome CV risk profile and a plausible mechanism to explain the CV risk, it is difficult to discern a credible rationale for keeping this medication on the market,” Gregory D. Curfman, MD, executive editor of NEJM, and colleagues wrote in an accompanying editorial.
The editorialists said these data must be weighed when considering the potential benefits of weight loss in any patient taking sibutramine. At 1 year, patients lost an average of 4.3 kg but regained 0.5 kg later, equating a net loss of less than 4 kg.
On Sept. 15, an FDA advisory committee is slated to discuss the SCOUT data and to decide whether additional regulatory action is needed for sibutramine.
The study was sponsored by Abbott.