At the American College of Cardiology Scientific Sessions in New Orleans this week, results were presented from the PROVE-IT trial, a study comparing clinical outcomes with two different statin regimens - standard-dose pravastatin (Pravachol) vs. high-dose atorvastatin (Lipitor). Over 4000 patients with elevated LDL cholesterol levels, hospitalized for either acute heart attacks or unstable angina, were randomized to receive either pravastatin 40 mg/day or atorvastatin 80 mg/day. The pravastatin was designed to reduce LDL cholesterol to 100 mg/dl, which according to the guidelines is the target LDL level for such patients. In contrast, the high-dose atorvastatin was designed to reduce LDL cholesterol levels to 70 mg/dl, substantially lower than the "official" target set by guidelines. The investigators followed patients for up to 2 years, and tabulated significant clinical events including overall mortality, heart attacks, unstable angina, the need for revascularization, and stroke.
Patients treated with pravastatin achieved LDL cholesterol levels of 92 mg/dl on average, while those treated with atorvastatin achieved substantially lower levels - an average of 62 mg/dl. These levels were in line with what was predicted by the designers of the study.
In terms of clinical outcome, patients treated with high-dose atorvastatin had significantly fewer significant clinical events than those treated with pravastatin. The relative risk of experiencing a significant clinical event was reduced by 16% in the atorvastatin group, and this result was highly significant statistically. The risk of statin-related side effects was not significantly different between the two groups.
The PROVE-IT study, when added with results from the recently reported REVERSAL study, offers compelling evidence that reducing LDL levels substantially lower than currently recommended under official guidelines, at least in patients with proven and recently active coronary artery disease, is beneficial. Whether these results are due purely to the lower LDL levels, or are in some way specifically related to the use of atorvastatin, is not entirely clear, however.
This study, like most studies involving statin drugs, was sponsored by a drug company. Often, this fact causes some observers to give less weight to a study's results than they might otherwise give. However, in the case of PROVE-IT, the sponsor was Bristol-Myers Squibb, the makers of pravastatin - not Pfizer, the makers of atorvastatin. The study was designed to disprove the suggestion some were making that a "stronger" statin would be better for patients than pravastatin. (Indeed, the acronym of the study, PROVE-IT, even suggests the sort of challenge one might hear on the playground.)
Thus, we have here the extremely unusual case of the sponsor's drug losing out -big time - to the non-sponsor's drug. This sort of outcome is highly unusual since the sponsors get to approve (or reject) the design of any trial they're paying for - and thus tend to pay for only trials they believe are likely to vindicate their product. In other words, PROVE-IT wasn't supposed to turn out this way. If anything, this fact should lend even more credence to the outcome of this study.
