Pharmacological trials: primary and secondary prevention of coronary heart disease

Abstract

This brief overview of outcome in studies on the primary and secondary prevention of CHD with drugs influencing cholesterol-lipid-lipoprotein metabolism or with platelet-influencing drugs indicates the following conclusions: (1) The central finding of the European trial on primary prevention with clofibrate—significant adverse effects on long-term mortality from all causes—compels the conclusion that this drug has no place in the broad effort to reduce CHD risk by lowering plasma lipids-lipoproteins. (2) No other disease endpoint data are as yet available on lipid reduction by other drugs for primary prevention; data from a U.S. cholestyramine trial are due in 1983 or 1984. (3) Results of the Coronary Drug Project with lipid-influencing drugs for secondary prevention in middle-aged post-MI men were negative for 5.0 and 2.5 mg/day mixed conjugated equine estrogens, and for dextrothyroxine, with early termination of all three of these regimens because of possible adverse effects. At the scheduled end of the trial, clofibrate showed no evidence of benefit and some signs of adverse effects. Nicotinic acid showed no evidence of benefit in regard to the primary CDP endpoint, all causes mortality, but it yielded a significant reduction in rates of nonfatal MI, nonfatal MI + CHD death, and stroke events. (4) Combined therapy with resin + nicotinic acid has a much greater capacity—over and above diet—than any single lipid-lowering drug to reduce markedly all atherogenic lipids-lipoproteins, while simultaneously raising HDL, but no disease endpoint data are available on benefit/risk ratio with this regimen. (5) Eight secondary prevention trials with platelet—influencing drugs indicate encouraging but not statistically significant results in five of six aspirin trials, in a trial with aspirin + dipyridamole, and in a trial with sulfinpyrazone. (6) Viewed in perspective, these discouraging data on lipid—influencing drugs for the primary and secondary prevention of CHD, and these equivocal data with platelet-influencing drugs for secondary prevention reinforce the fundamental conclusion that the main strategic thrust for the control of epidemic premature CHD must be primary prevention by nutritional-hygienic means, i.e., avoidance and correction of the lifestyles—especially “rich” diet and cigarette smoking, also sedentary living and incongruent behavior—that are the cause of the mass problem.