Statin use and 28-day survival in critically ill patients with non-acute myocardial infarction cardiogenic shock

Evidence regarding statin therapy in non-acute myocardial infarction cardiogenic shock is limited, and retrospective medication studies are vulnerable to treatment-timing bias. We examined whether the association between statin exposure and 28-day mortality persisted after accounting for the timing of statin administration. This retrospective cohort study used medical information mart for intensive care IV data from 991 adults with non-acute myocardial infarction cardiogenic shock. Statin exposure was ascertained from medication records that included atorvastatin and other statin agents. In the conventional time-fixed analysis, exposure was defined as receipt of any statin during the intensive care unit (ICU) stay. A 24-hour landmark analysis included patients alive at 24 hours, classified exposure according to statin administration during the 1st 24 hours, and began follow-up at the landmark. Separate 1:1 propensity-score matching (PSM) procedures and Cox models were performed for each exposure definition. Statin agent, 1st recorded dose, route, and time to 1st administration, together with specific mechanical-support, anti-inflammatory, and vasoactive co-treatments, were descriptively summarized in the matched cohorts. In the conventional cohort, 475 patients received a statin during the ICU stay and 516 did not; 255 patients per group remained after PSM. Conventional analyses suggested lower 28-day mortality before matching (adjusted hazard ratio [HR], 0.703; 95% confidence interval [CI], 0.539-0.918; P = .010) and after PSM (adjusted HR, 0.709; 95% CI, 0.507-0.993; P = .045). In the 24-hour landmark cohort, 311 patients received a statin within 24 hours and 680 did not; 255 patients per group remained after PSM. The association was absent before matching (adjusted HR, 1.127; 95% CI, 0.854-1.487; P = .398) and after PSM (adjusted HR, 1.190; 95% CI, 0.833-1.701; P = .339). Atorvastatin was the predominant 1st statin in both matched exposed groups. In 4-category analyses, the apparent benefit among new initiators in conventional models disappeared after the 24-hour landmark definition was applied. The apparent survival advantage associated with conventional time-fixed statin exposure was not reproduced after treatment timing was addressed. These findings do not support an independent 28-day survival benefit from statin administration within the 1st 24 hours of ICU admission and highlight the potential influence of immortal-time, treatment-selection, and co-treatment biases.