Cholesterol reduction yields clinical benefit. A new look at old data.
BACKGROUND
There has been a continuing debate about the overall benefit of cholesterol lowering. We performed a novel meta-analysis of all randomized trials of more than 2 years' duration (n = 35 trials) to describe how coronary-heart-disease (CHD), non-CHD, and total mortality are related to cholesterol lowering and to type of intervention.


RESULTS
The analytic approach was designed to separate the effects of cholesterol lowering itself from the other effects of the different types of intervention used. For every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% (P < .002) and total mortality by 10% (P < .03). Cholesterol lowering had no effect on non-CHD mortality. Certain types of intervention had specific effects independent of cholesterol lowering. Fibrates (clofibrates, 7 trials; gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P < .01) and total mortality by about 17% (P < .02). Hormones (estrogen, 2 trials; dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P < .04), non-CHD mortality by about 55% (P < .03), and total mortality by about 33% (P < .01). No specific effects independent of cholesterol lowering were found due to diet (n = 11) or other interventions (resins, 5; niacin, 3; statins, 2; partial ileal bypass, 1).


CONCLUSIONS
The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality.
Gould
A L
AL
Merck Research Laboratories, West Point, Pa 19486, USA.
Rossouw
J E
JE
Santanello
N C
NC
Heyse
J F
JF
Furberg
C D
CD
D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D002994:Clofibrate / Q000627:therapeutic use*; D003327:Coronary Disease / Q000401:mortality* / Q000517:prevention & control; D003918:Dextrothyroxine / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000628:therapy*; D008297:Male
D002791:Cholesterol, Dietary; D004967:Estrogens; D003918:Dextrothyroxine; D002784:Cholesterol; D002994:Clofibrate; D015248:Gemfibrozil