news
Cancer Risk and the use of Ezetemibe (Ezetrol)
September 3rd, 2008
Recent data from the simvastatin and ezetimibe in aortic stenosis (SEAS) study have shown that there were significantly more cases of cancer in those patients taking both ezetimibe and simvastatin together than in those treated with just placebo. There were 101 cases of cancer in 944 people treated with simvastatin and ezetimibe, taken together, giving a 2.7% a year risk of fatal and non fatal cancer and a 0.9% risk of death from cancer, while there were only 65 cases of 929 treated in the placebo group and this difference was significant.
The New England Journal of Medicine has now published online an interim analysis of the cancer data in two other trials -- the Improved Reduction in high-risk subjects presenting with acute coronary syndromes (IMPROVE-IT) and the Study of Heart And Renal Protection (SHARP) trials. In IMPROVE-IT and SHARP, there were 313 cases of cancer in 10,319 treated with simvastatin and ezetimibe while in the placebo group there were 326 cases in 10,298 treated and this was of course not a significant difference. So with much larger numbers of patients and at least three years of follow-up, there was no increased risk of incident cancer or cancer mortality. If all three trials are combined, there remains an increased risk of death from cancer in the active treatment arm. This data has been presented to the Food and Drug Administration (FDA) and a review has stated that patients should not stop taking simvastatin and ezetimibe or any other cholesterol lowering drug.
An analysis of these two ongoing studies using the combination of ezetimibe and simvastatin by Sir Richard Peto of the Clinical Trials Service unit in Oxford, published on line in the reputable New England Journal of Medicine, has found no increased risk suggesting that there is a real possibility that the data from the SEAS study is likely to be the play of chance rather than a real finding. However, in an accompanying editorial in the New England Journal of Medicine, uncertainty about the safety and efficacy of ezetimibe was made. The editorialists wrote: "Although the Oxford group may ultimately prove to be correct, it is appropriate to raise a note of caution. Whether the increased risk is due solely to the play of chance is uncertain. Ezetimibe interferes with the gastrointestinal absorption not only of cholesterol but also of other molecular entities that could conceivably affect the growth of cancer cells. The fact that all three trials, taken together, showed an increase in cancer mortality with ezetimibe should not be assumed to be a chance finding until further data are in”.
Dr Ralph Abraham comments: “I can imagine the concern generated by this report in both patients and specialists but it is clear that there is insufficient data to make an immediate judgment on the safety of ezetimibe. I always use ezetimibe as an ‘add on’ drug to a statin and selectively recommend it for patients who are already at increased risk of premature heart attack. This drug tends to get used when patients are unable, using maximum doses of strong statins, to achieve sufficiently low LDL targets or who are unable to tolerate high doses of statins for whatever reason. I will continue to take ezetimibe myself and I continue to believe that ultra low LDL cholesterol levels are the best way to reverse arterial thickening. For many patients the risk of an early heart attack is a more pressing medical issue. Patients should be made aware of these findings and they should discuss any concerns they have over continuing medication with ezetimibe with their consultant physician. Under no circumstances should they ever stop taking their statin”.
Link:
http://www.ctsu.ox.ac.uk/news/seas-slides-richard-peto.pdf
Rossebo AB, Pedersen TR, Borman K et al. Intensive lipid loweringwith simvastatin and ezetimibe in aortic stenosis. New England Journal of Medicine; Sept 2nd 2008
Peto R, Emberson J, Landray M et al. analysis of cancer data from three ezetimibe trials. N Engl J Med 2008; Sept 2nd 2008
Drazen JM, D’Agostino RB, Ware JH ezetimibe and cancer – an uncertain association. N Eng J Med 2008; Sept 2nd 2008
