Gender-based mortality follow-up from the program on the surgical control of the Hyperlipidemias (POSCH) and meta-analysis of lipid intervention trials: Women in POSCH and other lipid trials

Objective: The authors assessed the clinical results of lipid-lowering therapy in women. Summary Background Data: The Program on the Surgical Control of the Hyperlipidemias (POSCH) has demonstrated that 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. Methods: A review and meta-analysis were performed of the seven primary or secondary lipid/atherosclerosis intervention trials-including POSCH-published in the English language literature that included women and published results in women separate from the results in men or in the entire trial population. The main outcome measure analyzed was overall mortality. Results: The Scottish Physicians Clofibrate Study, the Newcastle upon Tyne Clofibrate Study, and the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I). Trial may have demonstrated a possible benefit in ACHD prognosis from effective lipid intervention in women. The other four available trials did not. The Minnesota Coronary Survey reported a 15.6% increase in overall mortality rate and a 30.6% increase in a combined cardiovascular endpoint rate in the lipid intervention group. The Upjohn Colestipol Study demonstrated statistically significant reductions in overall and ACHD mortality in the men, but not in the women. The Scandinavian Simvastatin Survival Study (4S) showed highly statistically significant reductions in overall and ACHD mortality in the total trial population, but not in the 827 women in this study. For the 78 women in POSCH, there was no evidence of clinical benefit in the lipid intervention group. Subjecting these seven studies to meta-analysis for overall mortality, a statistically significant reduction in this clinical endpoint was observed in the men, but not in the women. Assuming independent binomial distributions, the probability of obtaining statistical significance, with a two-sided alpha of 0.05, in a study of 7066 women (the combined number of women in the seven trials) would be >0.90 against an alternative of the magnitude observed in men. Conclusions: These observations have at least two possible interpretations: either the mechanism of coronary obstruction is different in men than in women, or the mortality rate in the women in the reviewed studies is too low for a statistically significant result. Nonetheless, the available clinical trial data fail to demonstrate any overall mortality or other convincing clinical benefits from effective lipid intervention in women.