SCOUT bevestigd cardiale bijwerkingen sibutramine

Nieuws - 6 sep. 2010

SCOUT confirms sibutramine adverse cardiac effects

06 September 2010

The weight loss drug sibutramine increases the risk for cardiovascular events among patients with pre-existing cardiovascular disease, show the results of the SCOUT study.

The SCOUT (Sibutramine Cardiovascular Outcomes) trial randomly assigned 10,744 overweight or obese patients with known cardiovascular disease to receive 6 weeks of treatment with sibutramine 10 mg/day followed by either continued sibutramine or placebo.

As reported in the New England Journal of Medicine, sibutramine treatment was associated with an increased risk for nonfatal myocardial infarction (MI) and stroke. The journal's editors, Gregory Curfman and colleagues, noted that several weight loss drugs have previously been withdrawn due to unwanted cardiovascular side effects. "In each case, the cardiovascular risk was not fully evaluated until long after the drug was approved, underscoring the need for clinical outcomes studies that assess safety much earlier in the regulatory process," they said.

Sibutramine itself has been on the market in the USA since 1997. The SCOUT study enrolled patients between 2003 and 2009 and followed them up for an average of 3.4 years.

The patients lost an average of 2.6 kg during the lead-in phase, after which patients assigned to continued sibutramine lost a further 1.7 kg, on average, during the first 12 months, while those taking placebo regained an average of 0.7 kg. Thereafter, both groups showed slight weight regain.

Blood pressure declined by 4.7/1.7 mmHg during the lead-in phase and remained reduced, but patients who switched to placebo had a 1.2/1.4-mmHg greater reduction than those who remained on sibutramine.The primary outcome of nonfatal MI or stroke, resuscitated cardiac arrest, or cardiovascular death occurred in 11.4% of the sibutramine group versus 10.0% of the placebo group - a significant 16% increase.This difference was driven by increased rates of nonfatal MI and stroke, which were 4.1% and 2.6%, respectively, in the sibutramine group compared with a corresponding 3.2% and 1.9% in the placebo group. This equated to a 28% increase in MI risk and a 36% increase in stroke risk.

W Philip James (London School of Hygiene and Tropical Medicine, UK) and colleagues therefore conclude that sibutramine should "continue to be excluded from use in patients with preexisting cardiovascular disease."

But Curfman et al said that: "the investigators' conclusion is based on a narrow interpretation of the SCOUT data, in which only the patients with pre-existing cardiovascular disease had an increase in the risk of new cardiovascular events."

They called this a "defensible" interpretation, but noted that the European Medicines Agency recently decided that the benefits of sibutramine are outweighed by the risks, and suspended marketing authorization for the drug in the European Union.

Curfman and colleagues concluded: "Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome cardiovascular risk profile, and a plausible mechanism to explain the cardiovascular risk, it is difficult to discern a credible rationale for keeping this medication on the market."

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