On the principle that turnabout is fair play, investigators decided that claims against statins should be scrutinized as closely as claims in their favor. After all, when the efficacy of statins is touted, only one kind of supporting evidence will suffice—randomized controlled trials (RTCs) against placebo. But when statins are accused of causing side effects, the charges tend to stick, even if the best evidence comes from observational studies, which seldom have the power to differentiate between events caused by drugs and those that are simply a matter of chance.
Hoping to give statins a fair hearing, investigators based at the National Heart and Lung Institute, Imperial College, sifted through the results of 29 RTCs, which included data on adverse effects as well as the efficacy of statins in preventing primary and secondary cardiovascular disease. Most important, data on all adverse effects were recorded in both the treatment and control (placebo) arms of the studies.
The investigators channeled this data, which reflected the experiences of more than 80,000 patients, into a statistical model. Then they used the model to calculate the increase in risk for each side effect in the statin and placebo arms. The investigators found that only a small minority of symptoms reported on statins are genuinely due to the statins: Almost all would occur just as frequently on placebo.
This result appeared March 12 in the European Journal of Preventive Cardiology, in a paper entitled “What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice.” According to this paper, “Only development of new-onset diabetes mellitus was significantly higher on statins than placebo; nevertheless only one in five of new cases were actually caused by statins.”
The investigators assessed many other side-effects—nausea, renal disorder, myopathy, and rhabdomyolysis (muscle breakdown), muscle ache, insomnia, fatigue, and gastrointestinal disturbance. Although these side effects are commonly attributed to statins, none of them appeared, on closer scrutiny, to be any more common in the statin arms of the RCTs than in the placebo arms.
“Patients and doctors need clear reliable information about benefits and risks to make informed decisions,” the study’s authors wrote, adding that those reporting symptomatic side effects during statin therapy need reliable confirmation that a symptom is truly caused by the drug. “Clinicians often assume symptoms occurring with statins are caused by statins, encouraging discontinuation.”
A press release issued by the European Society of Cardiology noted that the study was performed without funding from any agency in the public, commercial or not-for-profit sectors. It also included direct quotes from the study’s first author, Dr. Judith Finegold, including an acknowledgment that many patients do report symptoms with statins.
"We clearly found that many patients in these trials—whose patients are usually well-motivated volunteers who didn’t know if they were getting a real or placebo tablet—that many did report side-effects while taking placebo,” said Dr. Finegold. “In the general population, where patients are being prescribed a statin for an asymptomatic condition, why would it be surprising that even higher rates of side effects are reported?”
“Most people in the general population, if you repeatedly ask them a detailed questionnaire, will not feel perfectly well in every way on every day. Why should they suddenly feel well when taking a tablet after being warned of possible adverse effects?” Dr. Finegold offered additional comments on the implications of the study’s results. Rather than add weight to the case for wider prescription of statins, she said, the results “will help improve the patient-doctor consultation.”
“We believe that patients should be empowered to make their own decisions, but we must first make sure they have top-quality unbiased information,” Dr. Finegold concluded. “This is why we call on drug regulators to highlight in the long lists of side effects those few whose rate is incrementally greater than that experienced with a dummy tablet.”