CLINICAL STUDIES
Influence of baseline lipids on effectiveness of pravastatin in the CARE trial
Marc A. Pfeffer, MD, PhD, FACCa,
Frank M. Sacks, MDa,
Lemuel A. Moyé, MD, PhD*,
Cara East, MD ,
Steven Goldman, MD, FACC ,
David T. Nash, MD, FACC ,
Jacques R. Rouleau, MD, FACC||,
Jean Lucien Rouleau, MD, FACC¶,
Bruce A. Sussex, MD, FACC#,
Pierre Theroux, MD, FACC¶,
Ron J. Vanden Belt, MD, FACC** and
Eugene Braunwald, MD, FACCa
a Department of Medicine, Brigham and Women’s Hospital and Harvard School of Public Health, Boston, Massachusetts, USA
* Department of Medicine University of Texas School of Public Health, Houston, Texas, USA
Department of Medicine Baylor University, Dallas, Texas, USA
Department of Medicine Veterans Affairs Medical Center, Tucson, Arizona, USA
Department of Medicine State University of New York Health Science Center, Syracuse, New York, USA
|| Department of Medicine Laval Hospital, Ste-Foy, Quebec, Canada
¶ Department of Medicine Montreal Heart Institute, Quebec, Canada
# Department of Medicine Health Sciences Center, St. John’s, Newfoundland, Canada
** Department of Medicine Michigan Heart and Vascular Institute (author deceased), USA
Manuscript received April 29, 1998;
revised manuscript received August 5, 1998,
accepted September 10, 1998.
Address for correspondence: Dr. Marc Pfeffer, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
mapfeffer{at}bics.bwh.harvard.edu
Objectives. We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study.
Background. The CARE study cohort provided a relatively unique opportunity to examine the relation between lipid levels and clinical events in a post–myocardial infarction (MI) population with relatively low cholesterol and low density lipoprotein (LDL) cholesterol values.
Methods. There were 4,159 patients with a previous infarct and a total cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and triglyceride level <350 mg/dl randomly allocated to placebo (n = 2,078) or pravastatin 40 mg/day (n = 2,081). Time to either coronary death or nonfatal MI (primary end point) or to the secondary end point, which included undergoing a coronary revascularization procedure, was determined as a function of baseline lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride levels).
Results. Quartile analysis indicated important effects for LDL cholesterol, in which a higher LDL was associated with greater cardiac event rates (in the placebo group, every 25-mg/dl increment in LDL was associated with a 28% increased risk [5% to 56%, p = 0.015]) in the primary event. The differential event rates with respect to baseline LDL cholesterol for placebo and pravastatin groups reduced the difference in clinical outcomes at lower LDL cholesterol levels. In both the placebo and pravastatin groups, an inverse relation between baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline HDL cholesterol level was associated with a 10% [0% to 19%, p = 0.046] increase in coronary death or nonfatal MI).
Conclusions. Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.
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Abbreviations and Acronyms
| | CARE | = Cholesterol And Recurrent Events | | CI | = confidence interval | | HDL | = high density lipoprotein | | HMGs | = 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors | | LDL | = low density lipoprotein | | MI | = myocardial infarction | | 4S | = Scandinavian Simvastatin Survival Study |
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