The combination did reduce the incidence of atherosclerotic events alone and the need for coronary artery bypass surgery in one of the study’s two secondary endpoints.
The SEAS study, whose headline results were first reported at a press conference in London in July, included 1873 patients from centres throughout northern Europe. They had mild to moderate, asymptomatic aortic disease, and were randomised to receive either the simvastatinezetimibe combination or placebo.
After four years of follow-up, the data showed that therapy did not reduce the primary composite outcome of combined aortic-valve and ischemic events.
Commenting on the results, Professor Terje Pedersen (Ulleva University Hospital, Oslo, Norway) suggested that treatment may have been initiated too late in the course of the disease to affect further progression. “It is also possible that high levels of LDL cholesterol are just a marker for progression of stenosis,” he added.
Another large trial, ASTRONOMER is looking at the same question and is due to report at the ACC next year. “If that too is neutral, it will be the end for LDL therapy in aortic stenosis,” said Pedersen.
The SEAS study has sparked political and regulatory interest following suggestions of an increased cancer risk associated with the simvastatin-ezetimibe combination. Yesterday, Pedersen reported a total of 105 cancer cases in the treatment group compared with 70 among those on placebo - up from 93 and 65 disclosed at the London press conference.
The full SEAS report was published simultaneously online by the New England Journal of Medicine yesterday, along with a metaanalysis of cancer data from other trials with the simvastatinezetimibe combination. It concluded that the results “do not provide credible evidence of any adverse effect on cancer”.
A NEJM editorial, however, pointed out that ezetimibe “could conceivably affect the growth of cancer cells”. Thus, for the NEJM, the association between ezetimibe and cancer is still “uncertain”.