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(Circulation. 2000;102:1893.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Effect of Pravastatin on Coronary Disease Events in Subgroups Defined by Coronary Risk Factors

The Prospective Pravastatin Pooling Project

Frank M. Sacks, MD; Andrew M. Tonkin, MD; James Shepherd, MD; Eugene Braunwald, MD; Stuart Cobbe, MD; C. Morton Hawkins, DSc; Anthony Keech, MD; Christopher Packard, DSc; John Simes, MD; Robert Byington, PhD; Curt D. Furberg, MD; for the Prospective Pravastatin Pooling Project Investigators Group

From the Brigham and Women’s Hospital (F.M.S., E.B.), Harvard Medical School (F.M.S., E.B.), and Harvard School of Public Health (F.M.S.), Boston, Mass; National Heart Foundation (A.M.T.), Melbourne, Australia; University of Glasgow (J.S., S.C., C.P.), Glasgow, Scotland; University of Texas School of Public Health, Houston (C.M.H.); University of Sydney (A.K., J.S.), Sydney, Australia; and Wake Forest University (R.B., C.D.F.), Winston Salem, NC.

Correspondence to Dr F. Sacks, Nutrition Department, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu

Background—Previous trials have had insufficient numbers of coronary events to address definitively the effect of lipid-modifying therapy on coronary heart disease in subgroups of patients with varying baseline characteristics.

Methods and Results—The data from 3 large randomized trials with pravastatin 40 mg were pooled and analyzed with the use of a prospectively defined protocol. Included were 19 768 patients, 102 559 person-years of follow-up, 2194 primary end points (coronary death or nonfatal myocardial infarction), and 3717 expanded end points (primary end point, CABG, or PTCA). Pravastatin significantly reduced relative risk in younger (<65 years) and older (65 years) patients, men and women, smokers and nonsmokers, and patients with or without diabetes or hypertension. The relative effect was smaller, but absolute risk reduction was similar in patients with hypertension compared with those without hypertension. Relative risk reduction was significant in predefined categories of baseline lipid concentrations. Tests for interaction were not significant between relative risk reduction and baseline total cholesterol (5% to 95% range 177 to 297 mg/dL, 4.6 to 7.7 mmol/L), HDL cholesterol (27 to 58 mg/dL, 0.7 to 1.5 mmol/L), and triglyceride (74 to 302 mg/dL, 0.8 to 3.4 mmol/L) concentrations, analyzed as continuous variables. However, for LDL cholesterol, the probability values for interaction were 0.068 for the prespecified primary end point and 0.019 for the expanded end point. Relative risk reduction was similar throughout most of the baseline LDL cholesterol range (125 to 212 mg/dL, 3.2 to 5.5 mmol/L) with the possible exception of the lowest quintile of CARE/LIPID (<125 mg/dL) (relative risk reduction 5%, 95% CI 19% to -12%).

Conclusions—Pravastatin treatment is effective in reducing coronary heart disease events in patients with high or low risk factor status and across a wide range of pretreatment lipid concentrations.

Key Words: coronary disease • drugs • lipids • lipoproteins • meta-analysis

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