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Pravastatin in Acute Coronary Treatment - PACT (Pravastatin)
Description:
The goal of the trial was to evaluate the safety and efficacy of early treatment with pravastatin compared with placebo in patients with recent acute coronary syndrome (ACS).
Study Design
Study Design:
Patients Enrolled: 3,408
Mean Follow Up: 30 days
Mean Patient Age: Mean age 61 years
Female: 24
Patient Populations:
Age 18-85 years, acute MI (ST or non-ST elevation) or unstable angina, and onset of symptoms within 24 hours
Exclusions:
Statin therapy before their event (although other lipid-lowering therapies allowed), participation in any other clinical trial or the use of an investigational drug within the previous 30 days, planned coronary revascularization or cardiac transplantation, severe renal or hepatic disease or other severe disease, drug- or alcohol-related problems, gastrointestinal disease or a history of gastrointestinal surgery that might affect drug absorption, known hypersensitivity or previous serious adverse reactions to statin therapy, or women of child-bearing potential
Primary Endpoints:
Composite of death, acute MI (other than the index event), and readmission to hospital with unstable angina by 30 days
Secondary Endpoints:
Causes of death, acute MI other than the index event, and readmission to hospital for angina in the first month, urgent or unscheduled revascularization procedures, and other nonfatal cardiovascular events
Drug/Procedures Used:
Patients were randomized in a double-blinded manner to pravastatin (n=1,710) or placebo (n=1,698), with the first dose taken within 24 hours of the onset of symptoms. Treatment was continued once daily for four weeks. The initial dose of pravastatin was 20 mg (n=720), but was changed to 40 mg early in the trial (n=990).
Principal Findings:
The confirmed index event was acute myocardial infarction (MI) in 65.1% of patients and unstable angina in 30.3%.
The trial was designed to enroll 10,000 patients with 1,200 endpoints, but was discontinued early due to difficulty in recruiting. The primary endpoint of death, MI, or readmission for unstable angina by 30 days was 11.6% in the pravastatin arm and 12.4% in the placebo group (p=0.48). The event rate in the 720 patients randomized to 20 mg pravastatin before the dose change was 12.3% and in the 40 mg group (n=990) after the dose change was 11.1%. There was no difference in any component of the composite event for the pravastatin versus placebo comparison: death (0.6% vs. 1.3%), fatal MI (0.8% vs. 0.9%), nonfatal MI (3.1% vs. 2.8%), new unstable angina (2.4% vs. 2.2%), or recurrent unstable angina (4.7% vs. 5.2%).
There were no differences in serious adverse events between treatment arms. There was also no difference in abnormal liver function tests (1.5% for pravastatin vs. 1.1% for placebo, p=NS).
Interpretation:
Among patients with a recent ACS, early treatment with pravastatin was not associated with a difference in the composite endpoint compared with placebo, but the trial was discontinued early and as such, the analysis was underpowered. Prior larger trials such as CARE, 4S, and LIPID have demonstrated a benefit with statin therapy in patients with an ACS, but statin treatment in these trials was not started until several months after the event.
The present trial sought to evaluate the safety and efficacy of treatment with statins early post-ACS (24 hours). The MIRACL trial did evaluate the early use of statin therapy in ACS patients and showed a lower rate of the primary composite of death, MI, cardiac arrest, or angina with myocardial ischemia requiring rehospitalization in the early statin arm, driven primarily by a reduction in ischemia. However, patients were followed for 16 weeks, much longer than the present trial. The event rates in the present trial at the time of study discontinuation were as predicted in the trial design, further supporting the notion that the smaller than planned sample size in the present analysis was underpowered.
References:
Thompson PL, Meredith I, Amerena J, et al. Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial. Am Heart J 2004;148:e2.
Keywords: Liver Function Tests, Myocardial Infarction, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Pravastatin, Heart Arrest
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