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 rigorous 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 enrollment. Waiting for studies comparing the effects of low and high dosages of the same statin or the high dosage of two similarly potent and rapid lipid-lowering effect (as for instance atorvastatin and rosuvastatin), prudence has to be applied in the interpretation (and even more in the application) of these large and expensive study results, that have yet only confirmed the relevance of a more intensive lipid-lowering treatment in all patients affected by atherosclerosis-based coronary syndromes.
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D000069059:Atorvastatin; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003627:Data Interpretation, Statistical; D006538:Heptanoic Acids; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D017063:Outcome Assessment, Health Care; D017035:Pravastatin / Q000008:administration & dosage*; D011758:Pyrroles; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D017035:Pravastatin