A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events.
BACKGROUND
The high-density lipoprotein (HDL) cholesterol level is a strong predictor of cardiovascular events in epidemiologic studies. Until recently, it has been less extensively studied as a therapeutic target.


OBJECTIVE
To assess the angiographic and clinical effects of a pharmacologic strategy to increase HDL cholesterol levels.


METHODS
Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1996.


METHODS
Outpatient specialty clinic of a large U.S. military medical center.


METHODS
143 military retirees younger than 76 years of age with low HDL cholesterol levels and angiographically evident coronary disease.


METHODS
Gemfibrozil, niacin, and cholestyramine or corresponding placebos, with aggressive dietary and lifestyle intervention at baseline.


METHODS
Change from baseline to 30 months and a composite measure of clinical events that included hospitalization for angina, myocardial infarction, transient ischemic attack and stroke, death, and cardiovascular procedures.


RESULTS
At baseline, mean (+/-SD) lipid values were as follows: total cholesterol, 5.1 +/- 0.8 mmol/L (196 +/- 31 mg/dL); low-density lipoprotein (LDL) cholesterol, 3.3 +/- 0.7 mmol/L (128 +/- 27 mg/dL); and HDL cholesterol, 0.9 +/- 0.2 mmol/L (34 +/- 6 mg/dL). Compared with placebo, the pharmacologically treated group experienced a 20% (95% CI, 14.8% to 24.3%) decrease in total cholesterol level, a 36% (CI, 28.4% to 43.5%) increase in HDL cholesterol level, a 26% (CI, 19.1% to 33.7%) decrease in LDL cholesterol level, and a 50% (CI, 40.5% to 59.2%) reduction in triglyceride levels. Focal coronary stenosis increased by 1.4% in the placebo group but decreased by 0.8% in the drug group (difference, -2.2 percentage points [CI, -4.2 to -0.1 percentage points]). A composite cardiovascular event end point was reached in 26% of patients in the placebo group and 13% of those in the drug group (difference, 13.7 percentage points [CI, 0.9 to 26.5 percentage points]). Side effects, particularly flushing and gastrointestinal intolerance, were more common in the drug group but rarely led to withdrawal from the study.


CONCLUSIONS
The study was small and used a composite clinical outcome. Whether improvements in angiographic findings were due to reductions in LDL cholesterol or increases in HDL cholesterol was not established. Flushing may have led to inadvertent unblinding in patients who were randomly assigned to active study drugs.


CONCLUSIONS
A combination regimen aimed at increasing HDL cholesterol levels improves cholesterol profiles, helps prevent angiographic progression of coronary stenosis, and may prevent cardiovascular events in some people who exercise regularly and eat low-fat diets.
Whitney
Edwin J
EJ
Heart and Vascular Institute of San Antonio, San Antonio, Texas 78217, USA.
Krasuski
Richard A
RA
Personius
Bradley E
BE
Michalek
Joel E
JE
Maranian
Ara M
AM
Kolasa
Mark W
MW
Monick
Erik
E
Brown
B Gregory
BG
Gotto
Antonio M
AM
D000368:Aged; D008076:Cholesterol, HDL / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000009:adverse effects / Q000627:therapeutic use; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000178:diet therapy / Q000628:therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005081:Exercise Therapy; D005260:Female; D015248:Gemfibrozil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects / Q000627:therapeutic use
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D002792:Cholestyramine Resin; D009525:Niacin; D015248:Gemfibrozil