REVERSAL and PROVE-IT: Are clinically oriented trials really better than “pure” scientific studies?

Recently, two large randomised clinical trials compared the effects of standard and intensive lipid-lowering treatment (Pravastatin 40 mg vs. Atorvastatin 40 mg b.i.d.) on patient prognosis after acute coronary syndromes—the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT), and on the atherosclerosis regression—the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL). Undoubtedly, the event–rate reduction and the atherosclerosis regression associated to intensive hypocholesterolemic treatment in these studies are impressive, however we would like to highlight some methodological concerns raised by both trials, more clinically oriented than planned to give rigourous answers to the scientist. The main problems of both studies are that they compare the effects of statins with different pleiotropic and pharmacokinetic properties and that the metabolic disorders that affect the studied patients have not been clearly described. Moreover, it is unclear if the cardiovascular disease history length was similar in the two treatment groups as well as the length and dosage of statin treatment of the about 25% of patients taking statins before the enrolment.