Odkazy a zdroje - Studie - POSCH
Program on the Surgical Control of the Hyperlipidemias
Buchwald H, Varco RL, Matts JP et al.
Effect of Partial Ileal Bypass Surgery on Mortality and Morbidity from Coronary Heart Disease in Patients with Hypercholesterolemia
Buchwald H, Varco RL, Matts JP et al. N Engl J Med 1990, 323:946-55.
Coronary artery disease, hypercholesterolemia
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.
Survivors of the first myocardial infarction documented by ECG 6 to 60 months before randomization, 30 to 64 years of age, were randomized to intervention group (partial ileal bypass procedure involving bypass of the distal 200cm of ileum of the distal third of the small intestine) or control group after baseline angiography and stratification according to total cholesterol levels, the lipoprotein phenotype, and the extent of coronary artery disease.
A total of 838 patients (90.7% men), average age at randomization 51 yrs, were enrolled into the study. The base-line total cholesterol level was 6,49mmol/l with average LDL-c level of 4,62mmol/l. 83.8% of the total study population had smoked cigarettes. Of the 421 patients assigned to surgery, 22 refused to undergo the operation. In 23 subjects reversal of the bypass surgery had to be performed during follow-up. 31.5% of the patients in the control group were taking lipid lowering medication at the end of the study while the corresponding figure in the surgery-group was 3.7%. Follow-up coronary angiograms were obtained in 80.7% of the control-group patients and 84.7 surgery-group patients.
The partial ileal bypass operation involves bypass of either the distal 200 cm or the distal third of the small intestine whichever is greater, with restoration of bowel continuity by an en-to side ileocecostomy.
Lipid-lowering drugs were discontinued in all participants at least six weeks prior to base-line lipid measurements.
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.