JACC Vol. 26, No. 5
November 1, 1995:1133-9
CORONARY ARTERY DISEASE
Pravastatin Limitation of Atherosclerosis in the Coronary Arteries
(PLAC I): Reduction in Atherosclerosis Progression and
BERTRAM PITT, MD, FACC, G. B. JOHN MANCINI, MD, FACC,*
STEPHEN G. ELLIS, MD, FACC,t HOWARD S. ROSMAN, MD, FACC,~: JONG-SOON PARK, PHD,§
MARK E. McGOVERN, MD, FACC,§ FOR THE PLAC I INVESTIGATORS
Ann Arbor and Detroit, Michigan; Vancouver, British Columbia, Canada; Cleveland, Ohio; and Princeton, New Jersey
Objectives. This study was designed to evaluate the effect of
pravastatin on progression of coronary atherosclerosis and isch-
emic events in patients with coronary artery disease and mild to
Background. Few clinical trial data support the use of lipid-
lowering therapy in patients with coronary artery disease and
mild to moderate elevations in cholesterol levels.
Methods. Four hundred eight patients (mean age 57 years) with
coronary artery disease and low density lipoprotein (LDL) cho-
lesterol _>130 mg/dl (3.36 mmol/liter) but <190 mg/dl ([4.91
retool/liter]) despite diet were randomized in a 3-year study to
receive pravastatin or placebo. Atherosclerosis progression was
evaluated by quantitative coronary arteriography.
Results. Baseline mean LDL cholesterol was 164 mg/dl (4.24
mmol/liter). Pravastatin decreased total and LDL cholesterol and
triglyceride levels by 19%, 28% and 8%, respectively, and in-
creased high density lipoprotein cholesterol by 7% (p _< 0.001 vs.
placebo for all lipid variables). Progression of atherosclerosis was
reduced by 40% for minimal vessel diameter (p = 0.04), particu-
larly in lesions <50% stenosis at baseline. There was a consistent
although not statistically significant effect on mean diameter and
percent diameter stenosis. There were also fewer new lesions in
those assigned pravastatin (p _< 0.03). Myocardial infarction was
reduced during active treatment (8 in the pravastatin group, 17 in
the placebo group; log-rank test, p _< 0.05; 60% risk reduction),
with the benefit beginning to emerge after 1 year.
Conclusions. In patients with coronary artery disease and mild
to moderate cholesterol elevations, pravastatin reduces progres-
sion of coronary atherosclerosis and myocardial infarction. The
time course of event reduction increases the potential for a
relatively rapid decrease in the clinical manifestations of coronary
artery disease with lipid lowering.
(J Am Coil Cardiol 1995;26:1133-9)
Reduction of total and low density lipoprotein (LDL) choles-
terol levels has been shown to be effective in slowing angio-
graphically assessed progression of coronary atherosclerotic
plaque and improving clinical outcome in studies of patients
with established coronary artery disease (2,3). Most of these
trials have used diet alone or in conjunction with multiple drug
regimens to reduce serum lipids in patients with relatively
From the University of Michigan Hospital, Ann Arbor, Michigan; *Vancou-
ver Hospital and Health Sciences Centre, University of British Columbia,
Vancouver, British Columbia, Canada; tCleveland Clinic Foundation, Cleve-
land, Ohio; :~Henry Ford Hospital, Detroit, Michigan; and §Bristol-Myers
Squibb Pharmaceutical Research Institute, Princeton, New Jersey. Drs. Pitt and
Mancini have served as consultants to Bristol-Myers Squibb, Princeton, New
Jersey. This study was supported by a grant from the Bristol-Myers Squibb
Pharmaceutical Research Institute, Princeton, New Jersey. It was presented in
part at the 43rd Annual Scientific Session of the American College of Cardiol-
ogy, Atlanta, Georgia, March 1994. A list of the PLAC I Investigators appears in
Manuscript received January, 25, 1995; revised manuscript received May 26,
1995, accepted June 2, 1995.
Address for correstx)ndence: Dr. Bertram Pitt, University of Michigan
Hospital, Division of Cardiology, Yaubman Center 3910-0366,1500 East Medical
Center Drive, Ann Arbor, Michigan 48109-0366.
severe hyperlipidemia (2-4). Despite evidence of a clinical
benefit, many physicians do not prescribe lipid-lowering ther-
apy for patients with established coronary artery disease (5). In
part, the failure to more vigorously detect and treat hyperlip-
idemia can be attributed to the need for adjustment of dosage,
complexity and side effects of multiple drug regimens and the
perceived modest benefit on clinical end points (i.e., cardio-
vascular morbidity and mortality) with strategies before the
availability of 3-hydroxy-3-methylglutaryl-coenzyme A reduc-
tase inhibitors (reduetase inhibitors). In addition, although
substantial evidence attests to a benefit of lipid-lowering
therapy for patients with marked hyperlipidemia and coronary
artery disease (2,4,6,7), data to support treating patients with
more moderately elevated cholesterol levels have not been as
convincing. The goal of the present study was to evaluate the
effect of a treatment regimen easily adaptable to clinical
practice (i.e., monotherapy with a reductase inhibitor, pravas-
tatin, in conjunction with a fat-restricted diet versus a fat-
restricted diet alone) on progression of coronary atherosclero-
sis in patients with mild to moderate hypercholesterolemia and
coronary artery disease.
©1995 by the American College of C ardioh)g~
JACC Vol. 26, No. 5
November 1. 1995:1133 9
PIT]? ET AL. 1139
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