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| |  Simvastatin Plus Ezetimibe Reduces Ischaemic Cardiovascular Events in Patients With Aortic Stenosis: Presented at ESC By Chris Berrie MUNICH, Germany -- September 5, 2008 -- Combination therapy with simvastatin and ezetimibe is well tolerated and safe and reduces the risk of ischaemic cardiovascular (CV) events but not the rate of progression of aortic valve disease in patients with mild to moderate aortic stenosis, according to research presented here at the European Society of Cardiology 2008 Congress (ESC). The international, multicentre, double-blind, randomised, placebo-controlled trial was presented on September 2 by Terje Pedersen, MD, PhD, Ulleval University Hospital, Oslo, Norway, on behalf of the Simvastatin Plus Ezetimibe in Aortic Stenosis study investigators. The results were published simultaneously online in the New England Journal of Medicine (DOI: 10.1056/NEJMoa0804602). "Epidemiology indicates that LDL [low-density lipoprotein] cholesterol level is a risk factor for developing aortic valve stenosis, and also several case-control studies have indicated that use of statins might improve prognosis in such patients," Dr. Pedersen explained. Dr. Pedersen and colleagues therefore enrolled 1,873 asymptomatic patients aged 45 to 85 years with valvular aortic stenosis and normal left ventricular systolic function. They excluded patients receiving statin therapy and those with coronary heart disease, diabetes, or other important valvular diseases. The primary endpoint of the study was major adverse CV events (MACE) related to aortic valve disease and ischaemic heart disease. Secondary endpoints were aortic valve events and ischaemic CV events. The researchers randomised 929 patients to placebo and 944 to simvastatin 40 mg plus ezetimibe 10 mg. Patients in the 2 groups had a mean age of 67.4 and 67.7 years, respectively; men comprised 61.2% and 61.5% of each group, respectively. Patients' baseline characteristics, medications, and echocardiography parameters were well balanced between treatment groups. In the intention-to-treat population, there was a 60% decrease in LDL cholesterol in the simvastatin/ezetimibe group after 8 weeks, maintained to 50% at median treatment duration of 4.5 years. The primary MACE endpoint did not show any significant effect of simvastatin/ezetimibe (hazard ratio [HR], 0.96), as was the case for the secondary endpoint of aortic valve events (HR, 0.97), for aortic valve replacement (HR, 1.00), all-cause mortality (HR, 1.04), and peak aortic jet velocity on echocardiography. Ischaemic CV events showed a significant benefit for simvastatin/ezetimibe over placebo (HR, 0.78; P = .024). "The majority of the ischaemic events were coronary artery bypass graftings, which occurred less frequently in the treated group, with a hazard ratio of 0.68 [P = .015]," Dr. Pedersen added. Rates of serious adverse events were similar in the 2 treatment groups, although the simvastatin/ezetimibe group had significantly more cases of new cancer (65 vs 102 events; P = .01) and all cases of cancer (70 vs 105; P = .01). This cancer incidence saw a trend for fatal cancer in the simvastatin/ezetimibe group compared with placebo (4.1% vs 2.5%; HR, 1.67; adjusted P = .06). Dr. Pedersen mentioned a previous meta-analysis of 2 large ongoing clinical trials with ezetimibe and simvastatin (the Study of Heart and Renal Protection and Improved Reduction of Outcomes: Vytorin Efficacy International Trial) and noted that "this meta-analysis did not confirm an increased risk of cancer in those 2 trials." Funding for this study was provided by Schering-Plough Corporation and MSD.
[Study title: Results From the SEAS (Simvastatin Plus Ezetimibe in Aortic Stenosis) Study. Abstract 3213bis]
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