The controversy over the now-infamous Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial continues as results were presented to at the European Society of Cardiology (ESC) Congress 2008 in Munich yesterday. More than four years of intensive lipid-lowering therapy with ezetimibe/simvastin (Vytorin; (Merck/Schering Plough Pharmaceuticals) did not slow the progress of aortic stenosis, researchers reported here.
The interim results were first reported at a press conference in London on July 21, 2008. The results showed the cholesterol-lowering medication was no better than placebo in reducing the primary end point of aortic-valve and cardiovascular events. The combination was significantly more effective than placebo in reducing the risk of secondary end points of nonfatal MI, coronary artery bypass graft (CABG) surgery, PCI, hospitalization for unstable angina, stroke, and cardiovascular death. This reduction, noted investigators, was driven largely by a reduction in CABG surgery.
The main debate amongst Cardiologists was the significantly increased occurrence of fatal or nonfatal cancer in patients treated with ezetimibe/simvastatin combination compared with those treated with placebo. The cancer findings triggered an independent analysis by Sir Richard Peto (Clinical Trials Service Unit, Oxford, UK) of not only the SEAS data, but also data from the IMPROVE-IT and SHARP studies - concluding that that there was no increased risk of incident cancer or cancer-mortality. The consensus from the SEAS investigators and Peto™s findings is that the increased cancer was due to chance, rather than a significant study finding.
The analyses have been submitted to the Food and Drug Administration (FDA) for its review. Recently, the FDA issued a statement informing clinicians about its investigation into the possible link between Vytorin and an increased risk of cancer. The FDA review stated patients should not stop taking Vytorin or any other cholesterol-lowering drug. A full safety report from the FDA is expected in 2009.