SUBGROUP ANALYSES OF THE MAJOR CLINICAL END-POINTS IN THE PROGRAM ON THE SURGICAL CONTROL OF THE HYPERLIPIDEMIAS (POSCH) - OVERALL MORTALITY, ATHEROSCLEROTIC CORONARY HEART-DISEASE (ACHD) MORTALITY, AND ACHD MORTALITY OR MYOCARDIAL-INFARCTION

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ilea l bypass surgery as the intervention modality. For this report, we ana lyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as tho se with: (1) an absolute z-value greater than or equal to 2.0 for the subgroup, if the absolute z-value for the overall effect was <2.0; and (3) an absolute z-value greater than or equal to 3.0 for the subgroup and a relative risk less than or equal to 0.5, if the absolute z-valu e for the overall effect was greater than or equal to 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found s even subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups fo r more than one endpoint, there were 13 individual subgroups with diff erential effects. Of these, seven demonstrated internal consistency ac ross endpoints, and five of these seven displayed external consistency with known ACHD risk factors and for biological plausibility: triglyc eride concentration greater than or equal to 200 mg/dl; cigarette smok ing; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the ov erall treatment effect, by the reduction of a single risk factor, hype rcholesterolemia, in patients with at least two major ACHD risk factor s was a provocative and an hypothesis-generating outcome of this analy sis. The clinical implications of this finding may lead to more aggres sive cholesterol intervention in patients with multiple ACHD risk fact ors.