The Program on the Surgical Control of the Hyperlipidemias (POSCH): Demonstration of the beneficial effects of treatment of hypercholesterolemia

Despite advances in treatment, coronary heart disease (CHD) remains the leading cause of morbidity and mortality in the western world. Hypercholesterolemia has been clearly established as a major CHD risk factor; however, conclusive evidence supporting the therapeutic benefit of cholesterol reduction has remained elusive. The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a prospective, randomized, controlled, clinical trial designed to assess whether reductions in total plasma cholesterol and low density lipoprotein (LDL) cholesterol would reduce overall mortality and the mortality and morbidity due to CHD in survivors of a single myocardial infarction. POSCH enrolled 838 hypercholesterolemic patients, with 417 randomized to treatment with the American Heart Association Phase 2 diet and 421 randomized to similar dietary treatment plus a partial ileal bypass. The mean follow-up interval was 9.7 years. Compared to the control group at 5 years, the intervention group had a 23.3% lower total plasma cholesterol, a 37.7% lower LDL cholesterol, and a 4.3% higher high density lipoprotein (HDL) cholesterol. Overall and CHD mortality were reduced, but these reductions did not achieve statistical significance. In patients with a left ventricular ejection fraction ≥ 50%, overall mortality was 36% lower in the intervention group (p = 0.021). The occurrence of the combined endopoint of CHD death or confirmed nonfatal myocardial infarction was reduced 35% (p < 0.0001). During follow-up, 137 control and 52 intervention group patients underwent coronary artery bypass grafting (61% reduction, p < 0.0001). Comparison of baseline coronary arteriograms with studies performed at 3, 5, 7 or 10 years after randomization consistently demonstrated decreased coronary artery disease progression and increased regression in the intervention group. There was no significant difference in non-atherosclerotic mortality between groups. The principal side effects of partial ileal bypass included diarrhea, kidney stones, gall stones, and intestinal obstruction. The POSCH results provide the strongest evidence to-date supporting the beneficial effects of intensive treatment of elevated total plasma cholesterol and LDL cholesterol levels in hypercholesterolemic survivors of a single myocardial infarction, particularly in those patients with preserved left ventricular function.