We wish to address an important issue that relates to the analysis of serious adverse events in the systematic review of statins for primary prevention by Tonelli and colleagues.1
In the results section, the authors indicate “… the pooled risk of serious adverse events did not differ significantly between treatment groups (RR 1.01, 95% CI 0.96–1.07; I2 = 8%).” Although we congratulate the authors for obtaining data on serious adverse events from 21 of 29 trials, we urge them to post the forest plot and raw data from this analysis on CMAJ’s website for use by other researchers. The pooled relative risk confirms the finding of the Therapeutics Initiative of the University of British Columbia, that total serious adverse events are not reduced by statins in the clinical setting of primary prevention.2,3 The Therapeutics Initiative concluded that statins do not have a proven net health benefit in primary prevention. The analysis by Tonelli and colleagues, which furnishes data on serious adverse events from more trials, strengthens that conclusion.
What does the estimate of relative risk for serious adverse events reported by Tonelli and colleagues mean in clinical terms? The RR of 1.01 implies that taking a statin increases the chance of dying, being admitted to hospital or being permanently disabled by a nonsignificant 1% as compared with placebo. A conservative assumption is that serious adverse events in those trials were more frequent in the statin group than in the placebo group.
Why do Tonelli and colleagues ignore the serious adverse events outcome in their conclusions? Perhaps the data create a dilemma for proponents of widespread statin use in primary prevention. How can statins cause a statistically significant reduction in all-cause mortality, nonfatal myocardial infarction and nonfatal stroke — all outcomes that represent serious adverse events and that should be counted as such within the data on serious adverse events reported in clinical trials — and yet not reduce total serious adverse events? This implies that statins increase the risk of other serious adverse events to negate the decreased risk in cardiovascular morbidity and mortality.
In summary, we consider that the most important finding in the meta-analysis by Tonelli and colleagues is that statins do not reduce total serious adverse events and thus do not provide a net health benefit in primary prevention.