This question can only be answered for the statins that have been properly examined in large, long-term trials. Clinicians can be certain that the known benefits clearly outweigh the known risks for simvastatin and pravastatin. Documentation for lovastatin is fairly convincing, but is still insufficient for atorvastatin and fluvastatin.
We take the position that large, long-term trials are desirable to evaluate individual drugs that are prescribed for lifelong use. Initial approval of the first member of a novel class of therapeutic agents that has potential important health care benefits, may in some cases be justified on the basis of surrogate efficacy. However, subsequent drugs with similar mechanisms of action should not be rushed through the approval process but receive careful consideration regarding their net risk-benefit ratio and optimal dose, prior to regulatory approval. The cerivastatin experience supports the position that unexpected serious adverse events may not be detected until a large number of patients have been exposed for an extended period of time.
In relative terms, it appears that cerivastatin was inferior to the other statins. In absolute terms, it is quite likely that the clinical benefit of cerivastatin, yet unproven, could outweigh the minimal risk of fatal rhabdomyolysis. Our assumption is that the regulatory agencies worldwide might have left cerivastatin on the market if it had been the only marketed statin. In the presence of other statins, in particular, simvastatin and pravastatin – cerivastatin was clearly inferior. Concerns about patient safety tipped the regulatory decision towards its withdrawal. It will be interesting to see if drug inferiority in the future will be an important factor in the regulatory decision-making process.
The issues raised in this commentary have implications, not only for the drug approval process but perhaps more importantly, for the public's faith in prescription drugs. Withdrawal of approved and widely used drugs such as cerivastatin, because of serious life-threatening side effects, erodes public confidence in the medical care system. A lack of confidence may, in part, be responsible for the increasing reliance of the general public on alternative medical therapies. Approval of any drug for lifelong use on the basis of just a few thousand patients is risky and may not serve the public, as illustrated by the experience with cerivastatin and several other recently withdrawn drugs.