Betty J. Hansen

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: Report of the program on the surgical control of the hyperlipidemias (posch)

BACKGROUND AND METHODS The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.

Program on surgical control of the hyperlipidemias (POSCH): Recruitment experience

The Program on Surgical Control of the Hyperlipidemias (POSCH) is an investigator-initiated NHLBI grant-funded secondary coronary heart disease intervention trial using partial ileal bypass (PIB) for lipid reduction. Randomization started in September 1975 and ended in July 1983 with enrollment of 838 participants (421 surgery, 417 controls). The trial is scheduled to reveal the atherosclerosis impact of the lipid changes in 1990, at which time the average individual in the program will have been followed for 9.6 years. Initially, the magnitude of the recruitment task was greatly underestimated. An area containing 500,000 people was judged to be sufficient to randomize one patient per month. Actually, a population of 2.4-10.5 million, depending upon proximity to a clinic, was needed to achieve this goal. The study design was changed in 1981, due to recruitment costs, with reduction of the number of individuals to be randomized from 1000 to 838 and with extension of the duration of minimum follow-up from 5 to 7 years. Only with the development of a uniform model clinic concept, with specified levels of performance calculated from actual recruitment data, did accrual of patients into the trial become predictable and achievable. Some of the recruitment delays in POSCH were related to problems, in part generic to the existent grant funding mechanism and associated with decisions made by NHLBI and its Advisory Council. These delays were manifested by denial of reallocation of approved funds to initiate replacement clinics for discontinued ones, an 18-month delay in implementation of a protocol change in lipid criteria suggested by the Data Monitoring Committee, and a 2-year delay in the starting date for the fourth active clinic.

Program on the surgical control of the hyperlipidemias (POSCH): Patient entry characteristics

The entry characteristics of patients in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized, controlled, clinical trial, are described in this article. The primary objective addressed by POSCH was whether lowering total plasma cholesterol by partial ileal bypass surgery results in a reduction in mortality and morbidity in post-myocardial infarction patients. Between 1975 and 1983, 838 patients between the ages of 30 and 64 years were randomized into POSCH. The mean age at entry was 51 years, and 91% of the patients were men. The mean time between myocardial infarction and entry was 2.2 years. The mean baseline total plasma cholesterol was 251 mg/dl, with a mean LDL-cholesterol of 179 mg/dl and a mean HDL-cholesterol of 40 mg/dl. Significant disease (greater than or equal to 50% occlusion) of one or more major coronary arteries was found in 91% of the patients. In addition to a description of the POSCH patient population at entry, comparisons of the POSCH patient population to populations of participants in other lipid-lowering trials are presented to provide a perspective on how POSCH relates to these trials.

Myocardial infarction and percent arteriographic stenosis of culprit lesion: report from the Program on the Surgical Control of the Hyperlipidemias (POSCH).

The objective of this study was to assess the percent stenosis of the culprit lesion responsible for subsequent myocardial infarction in the Program on the Surgical Control of the Hyperlipidemias (POSCH). It is unknown if the susceptible coronary artery culprit lesion responsible for an acute myocardial infarction is relatively large ( > or = 50% arteriographic stenosis) and hemodynamically significant ( > or = 70% stenosis), or small ( < 50%, stenosis) and asymptomatic. Certain necropsy and arteriography studies support the large progenitor lesion concept, and other arteriography studies support the small lesion hypothesis. We analyzed the coronary arteriogram immediately preceding a Q wave (transmural) myocardial infarction for the degree of stenosis of the suspected culprit lesion, which was selected by visual inspection of the coronary circulation supplying the electrocardiogram-defined area of myocardial infarction. There was no perceptible difference with respect to vessel segment distribution of culprit lesions or time to infarction between the 52 control-group patients and the 27 intervention-group patients. For the two groups combined (n=79), the predominantly involved segments were the middle right coronary artery and the proximal left anterior descending coronary artery. The time interval from the preceding coronary arteriogram closest to the index myocardial infarction ranged from 0 days to 10 years; however, 64.6% of the arteriograms were performed 2 years or less prior to the myocardial infarction. Only 5.1% of the patients in both groups combined had a culprit lesion stenosis < 50%, while 88.6% of the patients in both groups combined had a culprit lesion stenosis > or = 70%. The results strongly favor the large lesion hypothesis of causation for myocardial infarction. It is premature, however, to state that the relative size of the culprit lesion has been indisputably determined. The resolution of this problem has exceedingly important practical implications for the management of patients with known atherosclerotic coronary heart disease and for those asymptomatic individuals with silent atherosclerotic coronary heart disease.