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SEAS: Combination therapy did not lower aortic valve disease rate
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Results from the SEAS trial suggested that although the combination of ezetimibe and simvastatin reduced the risk for coronary artery disease events and lowered LDL, it did not reduce the rate of progression of aortic valve disease.Results also show a possible increased risk of cancer among patients taking the drug.
Researchers enrolled 1,873 patients with mild to moderate aortic stenosis into the randomized, placebo-controlled study. They assigned patients either placebo or an aggressive LDL-lowering therapy that included a combination of 40 mg/day simvastatin and 10 mg/day of ezetimibe (Vytorin, Merck). They followed the participants for up to four years.
The combination of simvastatin and ezetimibe lowered LDL by an average of 76 mg/dL (61%). The researchers also reported that 688 patients had one or more of the primary endpoint events. There was no difference between the placebo group and the treatment group for the combined primary endpoint of major CV events (333 vs. 355; HR=0.96; 95% CI, 0.83-1.12).
During subsequent safety analyses, 158 patients had serious adverse events attributed to cancer. A higher percentage of these incidents were reported in patients receiving simvastatin and ezetimibe (9.9%) than in the placebo group (7.0%; P=.05). Deaths were also higher in the combination group vs. placebo group (4.1% vs. 2.5%).
“The observed difference in cancer in the SEAS study is based on small numbers and could have occurred as a result of chance,” the researchers said in a press release.
The researchers provided an independent academic group the SEAS data. The group compared it with related ata from the SHARP trial, designed to evaluate the effects of simvastatin and ezetimibe in 9,400 patients with chronic kidney disease, and the IMPROVE-IT trial, designed to compare simvastatin and ezetimibe with simvastatin alone.
“The analysis of SHARP and IMPROVE-IT does not support the suggestion of an increase in cancer that was raised by subsidiary analyses of the relatively small numbers of cancers in the SEAS study,” the researchers said. – by Eric Raible
The SEAS trial failed to meet its primary endpoints, which is how we always judge a trial. It does not provide any additional evidence of a benefit from the drug. Nobody knows what to do with the signal of cancer. An effort was made to imply that this was not significant, but it certainly does not increase confidence in the drug. We are still waiting to see whether there is any evidence of a benefit on health outcomes.
– Steven Nissen, MD
Cardiology Today Editorial Board member