POSCH trial 25-year follow-up results: latest news from an old kid on the block

Evaluation of: Buchwald H, Rudser KD, Williams SE, Michalek VN, Vagasky J, Connett JE: Overall mortality, incremental life expectancy and cause of death in the Program on the Surgical Control of the Hyperlipidemia. Annal. Surg. 241, 1034–1040 (2010). The Program on the Surgical Control of the Hyperlipidemia (POSCH) trial was designed aiming to evaluate the effect of cholesterol reduction by ileal bypass on mortality in patients with previous myocardial infarction. The surgical procedure increases fecal loss of bile acids, promoting hepatocellular cholesterol deprivation and, as a result, induces an average 38% reduction of LDL-C and 4% increase in HDL-C, which held constant throughout the follow-up. In the last report, an analysis of the study after 25 years of follow-up demonstrated the persistence of the reduction of total and cardiovascular mortality in the surgical group, which were 18 and 8% lower, respectively, compared with the control group. Furthermore, cancer mortality was not different between groups, opposing the hypothesis of a causal association between cholesterol lowering and increases in the incidence of cancer. In this article, we discuss the rationale and findings of the POSCH trial over the past 25 years and their clinical and mechanistic implications.