Clinical investigations
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

https://doi.org/10.1016/j.ahj.2003.10.052Get rights and content

Abstract

Background

The efficacy of statin drugs after an acute coronary event is now well established, but the evidence for statin use in the early treatment of acute coronary events remains unclear.

Methods

We tested the effects of administering pravastatin within 24 hours of the onset of symptoms in patients with unstable angina, non–ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. Patient recruitment of 10,000 with 1200 end points was planned, but the trial was stopped early. A total of 3408 patients were randomly assigned to treatment with pravastatin (1710 patients) or matching placebo (1698 patients). Treatment was continued for 4 weeks. The primary end point of the study was a composite of death, recurrence of myocardial infarction, or readmission to hospital for unstable angina within 30 days of random assignment.

Results

The primary end point occurred in 199 of patients allocated to pravastatin (11.6%) and in 211 patients allocated to placebo (12.4%). A relative risk reduction of 6.4% favored allocation to pravastatin but was not statistically significant (95% CI, −13.2% to 27.6%). No adverse effects were seen.

Conclusions

We conclude that 20 to 40 mg of pravastatin can be safely administered within 24 hours of the onset of symptoms of an acute coronary event, with a favorable but not significant trend in outcome at 30 days compared with placebo.

Section snippets

Design

The trial was designed as a double-blinded, placebo-controlled, randomized, multicenter study to assess outcomes at 30 days in patients with an acute myocardial infarction (AMI) or unstable angina pectoris (UAP) randomly assigned to either pravastatin or placebo within 24 hours of the onset of chest pain.

Inclusion criteria

Patients were enrolled in the study within 24 hours of the onset of symptoms if they had electrocardiographic changes suggestive of an AMI or UAP. The diagnosis of an AMI was made on the basis

Study population

Three thousand four hundred eight patients were randomly assigned to the treatment arms of the study. The initial diagnosis at the time of random assignment was AMI in 2006 (58.9%) patients and UAP in 1402 (41.1%) patients. When biochemical markers and serial electrocardiographic changes were subsequently evaluated, the confirmed diagnoses were AMI in 2220 patients (65.1%), UAP in 1036 patients (30.3%), and other diagnoses in 152 patients (4.6%). Patients whose diagnosis was other than AMI or

Discussion

As well as lowering serum LDL concentrations, statins have been demonstrated to influence a number of other mechanisms that are potentially important in the treatment of acute coronary syndromes. Animal studies have revealed potential roles for statins in plaque stabilization by increasing collagen content of the unstable plaque12 and reducing macrophage activation and expression of matrix metalloproteinases.13 Reductions in plasma fibrinogen14 and thrombogenic factors have been demonstrated in

References (31)

  • MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individualsa randomised placebo-controlled trial

    Lancet

    (2002)
  • F.M Sacks

    Lipid-lowering therapy in acute coronary syndromes

    JAMA

    (2001)
  • G.C Fonarow et al.

    In-hospital initiation of lipid-lowering therapy for patients with coronary heart diseasethe time is now

    Circulation

    (2001)
  • U Stenestrand et al.

    Early statin treatment following acute myocardial infarction and 1-year survival

    JAMA

    (2001)
  • L.K Newby et al.

    SYMPHONY and 2nd SYMPHONY InvestigatorsSibrafiban vs Aspirin to Yield Maximun Protection From Ischemic Heart Events Post-acute Coronary Syndromes: early statin initiation and outcomes in patients with acute coronary syndromes

    JAMA

    (2002)
  • Cited by (0)

    Supported by Bristol-Myers Squibb, Australia.

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