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Program on the Surgical Control of the Hyperlipidemias - POSCH
Description:
Ileal bypass vs. diet for mortality in hypercholesterolemia.
Hypothesis:
Lowering of plasma cholesterol is directly related to a reduction in atherosclerosis risk.
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 838
Mean Follow Up: 9.7 years
Mean Patient Age: 51
Female: 9
Mean Ejection Fraction: 56.1
Patient Populations:
Men and women between 34 and 64 years of age
Sustained a single documented myocardial infarction (MI), 6 to 60 months before randomization.
After a minimum of six weeks of dietary fat and cholesterol restriction, 3-day mean total plasma cholesterol >220 mg/dL, or a LDL-cholesterol >140 mg/dL, if the total cholesterol was between 200 and 219 mg/dL.
Exclusions:
Unwillingness to participate
Failure to meet the cholesterol criteria
Inability to satisfy the MI criteria
Presence of diabetes
Basal, diastolic blood pressure >105 mmHg and basal, systolic blood pressure >180 mmHg on two or three consecutive readings determined in the sitting position at 1-5 minute intervals in the following order: right arm, left arm, right arm
Body weight >140% ideal body weight
Previous CABG, PTCA, or pacemaker implantation
Other excluding diseases and conditions including unstable angina, heart failure after withdrawal of controlling medications, dysrhythmias, conduction defects, cardiomegaly, etc.
Primary Endpoints:
Death from any cause.
Secondary Endpoints:
Fatal and nonfatal myocardial infarctions, serial electrocardiographic changes, and, most importantly, sequential coronary arteriography changes, necessity for revascularization.
Drug/Procedures Used:
Partial ileal bypass (PIB) and diet therapy.
Principal Findings:
An overall mortality rate of 10% occurred at 6.7 years in the control group and 9.4 years in the intervention group, for a gain in disease-free interval of 2.7 years in the intervention group (p = 0.032).
A coronary heart disease rate of 8% occurred at 7.2 years in the control group and 11 years in the intervention group, for a gain of 3.8 years (p = 0.046).
Twenty percent of patients demonstrated the combined endpoint of coronary heart disease mortality and confirmed nonfatal myocardial infarction at 5.9 years in the control group and 11.4 years in the intervention group, for a gain of 5.5 years (p < 0.001).
Twenty-five percent of patients underwent either coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty or heart transplantation at 5.4 years in the control group and 12.4 years in the intervention group, for a gain of 7 years (p < 0.001).
Women:
At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film).
Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate endpoints for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression.
At 5 years, there were statistically significant differences in overall mortality (P = .049) and mortality from ACHD (P = .03). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer.
Interpretation:
The marked lipid modification achieved by partial ileal bypass in the POSCH trial led to demonstrable increases in the disease-free intervals for overall mortality, coronary heart disease mortality, coronary heart disease mortality and confirmed nonfatal myocardial infarction, and coronary intervention procedures. For the clinician and the patient, estimation of disease-free intervals may be more relevant than assessment of differences in incidence rates and risk ratios.
The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.
Effective lowering of total cholesterol and low-density lipoprotein cholesterol in a postmyocardial infarction population significantly reduces atherosclerotic coronary heart disease (ACHD) mortality, ACHD mortality combined with a new confirmed nonfatal myocardial infarction, and the number of coronary artery bypass grafting and angioplasty procedures performed.
Significant differences in morbidity and mortality were preserved over a 5-year period following the trial.
References:
1. J Clin Epidemiol 1989;42:1111-27. Design and methods
2. Control Clin Trials 1991;12:314-39. Baseline characteristics
3. Ann Surg 1992;216:389-98. Effects in women
4. J Clin Epidemiol 1995;48:389-405. Subgroup analyses
5. J Am Coll Cardiol 1995;26:351-57. Disease-free intervals
6. Ann Surg 1996;224:486-98. Gender subgroups
7. Arch Int Med 1998;158:1253-61. Five-year follow-up
8. Atherosclerosis 1998;138(2):391-401. MI and culprit lesion stenosis
Keywords: Odds Ratio, Coronary Artery Disease, Neoplasms, Myocardial Infarction, Atherosclerosis, Follow-Up Studies, Dietary Fats, Hypercholesterolemia, Angioplasty, Balloon, Coronary, Heart Transplantation, Biomarkers, Coronary Angiography, Diet, Coronary Artery Bypass, Disease Progression
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