PROVE-IT TRIAL - CardiologyTrials.org

PROVE-IT TRIAL
Problem	Recent ACS (within 10 days)
Format	Double-blinded multi-center RCT
Treatment	Atorvastatin 80mg
Control	Pravastatin 40mg
Population	4162 patients
Inclusion criteria	Men and women who were at least 18 years old were eligible for inclusion if they had been hospitalized for an acute coronary syndrome â€” either acute myocardial infarction (with or without electrocardiographic evidence of ST-segment elevation) or high-risk unstable angina â€” in the preceding 10 days. Patients had to be in stable condition and were to be enrolled after a percutaneous revascularization procedure if one was planned. Finally, patients had to have a total cholesterol level of 240 mg per deciliter (6.21 mmol per liter) or less, measured at the local hospital within the first 24 hours after the onset of the acute coronary syndrome or up to six months earlier if no sample had been obtained during the first 24 hours. Patients who were receiving long-term lipid-lowering therapy at the time of their index acute coronary syndrome had to have a total cholesterol level of 200 mg per deciliter (5.18 mmol per liter ) or less at the time of screening in the local hospital.
Exclusion criteria	Patients excluded if they: Had coexisting condition that shortened expected survival to less than two years Receiving therapy with any statin at a dose of 80 mg per day at the time of their index event Taking lipid-lowering therapy with fibric acid derivatives or niacin that could not be discontinued before randomization Had received drugs that are strong inhibitors of cytochrome P-450 3A4 within the month before randomization Were likely to require such treatment during the study period (because atorvastatin is metabolized by this pathway) Had undergone percutaneous coronary intervention within the previous six months (other than for the qualifying event) or coronary-artery bypass surgery within the previous two months or were scheduled to undergo bypass surgery in response to the index event Had factors that might prolong the QT interval Had obstructive hepatobiliary disease or other serious hepatic disease Had an unexplained elevation in the creatine kinase level that was more than three times the upper limit of normal and that was not related to myocardial infarction Had a creatinine level of more than 2.0 mg per deciliter (176.8 Î_mol per liter).
Follow-up	18 to 36 months (mean, 24)
Primary endpoint	Composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalisation, revascularization (performed at least 30 days after randomisation), and stroke.
Secondary endpoint(s)	Risk of death from coronary heart disease, nonfatal myocardial infarction, or revascularization (if it was performed at least 30 days after randomization) The risk of death from coronary heart disease or nonfatal myocardial infarction The risk of the individual components of the primary end point -Death from any cause -MI -Unstable angina requiring rehospitalisation -Revascularisation >30d after randomisation -Stroke
Details	.
Brief summary:	Significantly reduced CVD events following MI with high-dose atorva vs. prava

PAPER: Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
Date	8 Apr 2004
Journal	N Engl J Med. 2004 Apr 8;350(15):1495-504.
Information	Non-inferiority study assessing -If lower LDL in ACS patients is associated with reduced CVD events -Efficacy and safety of aggressive LDL cholesterol lowering In patients already receiving statin -LDL unaffected by prava 40 -32% reduction by atorva 80 (p<0.001) Primary endpoint RRR of 16% for atorva 80 (26.3%->22.4%; p<0.005) -Benefit as early as 30 days -Pravastatin failed to meet equivalence Similar rates of discontinuation -Increased rate of abnormal LFT for atorva (3.3% vs 1.1% prava)