Target trial emulation of statin discontinuation in multimorbid older adults with polypharmacy

Background: The benefit of statins in multimorbid older adults is controversial. Prior observational studies evaluating statin discontinuation in older adults were retrospective cohorts, did not focus on multimorbidity, or lacked adjustment for geriatric syndromes. We aimed to assess the effect of statin discontinuation on cardiovascular and mortality outcomes using the target trial emulation framework. Methods: We conducted a prospective cohort study using data from the OPERAM trial in adults aged ≥70 years with ≥3 chronic conditions and ≥5 chronic drugs, comparing statin discontinuation to continuation. The primary composite outcome was cardiovascular events or all-cause mortality at 12 months. We calculated adjusted hazard ratios (HR) using weighted pooled logistic regressions without (model-A) and with adjustment for two geriatric syndromes (falls and weight loss; model-B). Results: Of 2668 person-trial units (mean age 78.5 years), 2533 (95%) continued and 133 (5%) discontinued statins. Discontinuation was associated with higher composite outcome risk (27% vs. 18%; HR model-A 1.53 [95% CI 1.14–2.06]; model-B 1.49 [1.12–1.99]). This was mainly attributable to increased non-cardiovascular deaths (20% vs. 11%; HR model-A 1.56 [1.08–2.27]; model-B 1.52 [1.06–2.19]); there was no clear evidence for an association with cardiovascular events (7% vs. 8%; HR model-A 1.36 [.86–2.14]; model-B 1.35 [.86–2.12]). Conclusion: In this first target trial emulation in a multimorbid older population, statin discontinuation was associated with increased risk of the composite of cardiovascular events or all-cause mortality, primarily driven by non-cardiovascular deaths. Geriatric syndromes did not modify these increased risks. Only clinical trials can clarify the safety of statin discontinuation.