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Continued from Previous……
Questions about Results of Randomized Clinical Trials (RCTs)
Most information, and excerpts, for this part has been taken from the published article Rabaeus M et al. Recent Flaws in Evidence-Based Medicine: Statin Effects in Primary Prevention and Consequences of Suspending the Treatment. J Controversies Biomed Res 2017;3(1):1–10. 1
Statin therapy is being promoted by the pharmaceutical companies as a protection against ischemic heart disease (IHD) complications. It therefore stands to reason that the statins should decrease cardiovascular as well as all-cause mortality, and possibly should increase life expectancy. However, the true effects of statin therapy on IHD complications and mortality, as presented in RCTs are under intense controversy. The controversy is particularly intense around the effects on primary prevention and consequences of discontinuation.
Primary prevention means that if a person is taking statin, she/he would possibly be prevented from developing heart disease. Consequences of discontinuation would possibly be seen in a patient already taking statins.
The number of dissenting and contesting voices is growing. It is openly being questioned whether the physicians, scientists and patients have been misled by the way the results of clinical trials have been presented.
The authors comment. “On April 2, 2016, investigators of the Heart Outcomes Prevention Evaluation (HOPE)-3 trial reported the main results of a randomized double-blinded trial testing the effects of rosuvastatin (10 mg per day against placebo) on the risk of cardiovascular complications. The authors concluded that cholesterol lowering with rosuvastatin “resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease”. The associated editorial concluded that HOPE-3 “adds to the evidence supporting statin use for primary prevention”.
“With all due respect, we think these statements should be seriously questioned. As recently underlined, the claims about efficacy (supposed to be high) and toxicity (supposed to be low) of statins are essentially based on RCTs published before 2005, which can be seriously criticized. Recent RCTs (published after 2005) are still equivocal, suggesting that even after 2005 basic methods of evidence-based medicine were still not fully and systematically respected (1). There are several ways of (intentionally or not) flawing RCT data, for instance, by not fully describing the raw data and/or only reporting partial data extracted from large database. Also, as the clinical files of randomized patients are quite easily accessible via Internet, unblinding is, although unproven, probably frequent. In consequence, health authorities are more and more precautious, and investigators are obliged to release increasing amounts of data, often performed in the form of “online supplementary materials.” Careful examination of all these released materials can provide information on the way the RCTs are conducted and analyzed. What about HOPE-3, the latest reported statin RCTs?”