New statin use, mortality, and first cardiovascular events in older US Veterans by frailty status

Abstract

Background: Statins are part of long-term medical regimens for many older adults. Whether frailty modifies the protective relationship between statins, mortality, and major adverse cardiovascular events (MACE) is unknown. Methods: This was a retrospective study of US Veterans ≥65, without CVD or prior statin use seen in 2002–2012, followed through 2017. A 31-item frailty index was used. The co-primary endpoint was all-cause mortality or MACE (MI, stroke/TIA, revascularization, or cardiovascular death). Cox proportional hazards models were developed to evaluate the association of statin use with outcomes; propensity score overlap weighting accounted for confounding by indication. Results: We identified 710,313 Veterans (mean age (SD) 75.3(6.5), 98% male, 89% white); 86,327 (12.1%) were frail. Over mean follow-up of 8 (5) years, there were 48.6 and 72.6 deaths per 1000 person-years (PY) among non-frail statin-users vs nonusers (weighted Incidence Rate Difference (wIRD)/1000 person years (PY), −24.0[95% CI, −24.5 to −23.6]), and 90.4 and 130.4 deaths per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, −40.0[95% CI, −41.8 to −38.2]). There were 51.7 and 60.8 MACE per 1000PY among non-frail statin-users vs nonusers (wIRD/1000PY, −9.1[95% CI, −9.7 to −8.5]), and 88.2 and 102.0 MACE per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, −13.8[95% CI, −16.2 to −11.4]). There were no significant interactions by frailty for statin users vs non-users by either mortality or MACE outcomes, p-interaction 0.770 and 0.319, respectively. Statin use was associated with lower risk of all-cause mortality (HR, 0.61 (0.60–0.61)) and MACE (HR 0.86 (0.85–0.87)). Conclusions: New statin use is associated with a lower risk of mortality and MACE, independent of frailty. These findings should be confirmed in a randomized clinical trial.