Back in July I wrote about a study (the so-called SEAS trial) in which two cholesterol agents (simvastatin and ezetimibe) taken in combination appeared to increase risk of cancer. The full results of this study were published this week in the New England Journal of Medicine [1] and can be read here.
Alongside this research, we have an analysis by some scientists from Oxford University who look at other data from two large trials (the so-called SHARP and IMPROVE-IT trials) which are ongoing, and were designed to assess the potential benefits of the simvastatin/ezetimibe combo [2]. You can read this here.
The analysis found:
Neither the SHARP or IMPROVE-IT trials showed a statistically significant association between the taking of simvastatin/ezetimibe and cancer incidence or mortality from cancer.
When all 3 trials were lumped in together (SHARP, IMPROVE-IT and SEAS), there was no increased incidence of cancer, but the risk of dying from cancer was increased by 45 per cent in those taking the medication (and this was statistically significant).
The feeling of the authors of this analysis is that the excess of cancer and cancer death thrown up by the data is just down to chance. A fluke. Part of their reasoning rests on the fact that when all 3 trials are taken together, there was no statistically significant increase in cancer incidence (just mortality). They also say there is no plausible mechanism for the link.
The fact that there is no plausible mechanism is a not a good defense of ezetimibe, I think. Just because can’t explain how something is happening does not mean it’s not happening. If scientists notice a new adverse effect from a drug, the challenge is then to explore it further in an attempt elucidate its mechanism (as well as its extent). I’m not sure it’s a good idea to use our ignorance as a reason to dismiss our findings. Also, it should be borne in mind that there is quite a lot of evidence linking low cholesterol levels with enhanced risk of cancer.
The results of the 3 trials are inconsistent. But it should be borne in mind that if one or both of these cholesterol-reducing drugs do cause cancer then the likelihood is that it’s going to take some time (several years, probably) for that effect to be seen. Notably, the SEAS trial lasted for 4 years, while SHARP and IMPROVE-IT trials lasted an average of 2.7 and one year respectively. These lengths of time are almost certainly not long enough for any real effect of cancer to be seen.
But I suppose what is noteworthy in all of this is just how readily it seems some scientists are prepared to abandon science when (apparently) it suits them. Results have come in which, when analysed scientifically and statistically, show a link between the taking of simvastatin and ezetimibe and cancer that are very unlikely to be due to chance. And then some scientists have turned round and claimed that the results are, actually, likely to be due to chance.
Not all doctors and scientists take this view, fortunately. An accompanying editorial [3] states: The fact that the combined data from all three trials showed an increase in cancer mortality with ezetimibe should not be assumed to be a chance finding until further data are in. That seems eminently sensible to me, as I hope it will to others who are resistant to the idea of dismissing scientific findings, however unpalatable.
References:
1. Rossebø AB, et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. NEJM Published on-line 2nd September 2008.
2. Peto R, et al. Analyses of cancer data from three ezetimibe trials. NEJM Published on-line 2nd September 2008.
3. Drazen JM, et al. Ezetimibe and cancer ” an uncertain association. NEJM Published on-line 2nd September 2008.
