Therapeutic Effects of Lowering Cholesterol

Therapeutic Effects of Lowering Cholesterol

Reducing cholesterol levels in healthy middle-aged men without CHD (primary prevention) reduces their risk in proportion to the reduction in LDL cholesterol and the increase in HDL cholesterol. Treated patients have statistically significant and clinically important reductions in the rates of myocardial infarctions, new cases of angina, and need for coronary artery bypass procedures. The West of Scotland Study showed a 31% decrease in myocardial infarctions in middle-aged men treated with pravastatin compared with placebo. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) study showed similar results with lovastatin. As with any primary prevention interventions, large numbers of healthy patients need to be treated to prevent a single event. The numbers of patients needed to treat (NNT) to prevent a nonfatal myocardial infarction or a coronary artery disease death in these two studies were 46 and 50, respectively. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study of atorvastatin in subjects with hypertension and other risk factors but without CHD also demonstrated a convincing 36% reduction in CHD events. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) showed a 44% reduction in a combined end point of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The NNT for 1 year to prevent one event was 169.

Primary prevention studies have found a less consistent effect on total mortality. The West of Scotland study found a 20% decrease in total mortality, tending toward statistical significance. The AFCAPS/TexCAPS study with lovastatin showed no difference in total mortality. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) also showed no reduction either in all-cause mortality or in CHD events when pravastatin was compared with usual care. Subjects treated with atorvastatin in the ASCOT study had a 13% reduction in mortality, but the result was not statistically significant. This study, however, was stopped early due to the marked reduction in CHD events. The JUPITER trial demonstrated a statistically significant 20% reduction in death from any cause. The NNT for 1 year was 400.

In patients with CHD, the benefits of cholesterol lowering are clearer. Major studies with statins have shown significant reductions in cardiovascular events, cardiovascular deaths, and all-cause mortality in men and women with coronary artery disease. The NNT to prevent a nonfatal myocardial infarction or a coronary artery disease death in these three studies were between 12 and 34. Aggressive cholesterol lowering with these agents causes regression of atherosclerotic plaques in some patients, reduces the progression of atherosclerosis in saphenous vein grafts, and can slow or reverse carotid artery atherosclerosis. Meta-analysis suggests that this latter effect results in a significant decrease in strokes. Results with other classes of medications have been less consistent. For example, gemfibrozil treatment subjects had fewer cardiovascular events, but there was no benefit in all-cause mortality when compared with placebo.

The disparities in results between primary and secondary prevention studies highlight several important points. The benefits and adverse effects of cholesterol lowering may be specific to each type of drug; the clinician cannot assume that the effects will generalize to other classes of medication. Second, the net benefits from cholesterol lowering depend on the underlying risk of CHD and of other disease. In patients with atherosclerosis, morbidity and mortality rates associated with CHD are high, and measures that reduce it are more likely to be beneficial even if they have no effect—or even slightly harmful effects—on other diseases.

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