Statin therapy and 1-year mortality in non-ischaemic acute myocardial injury: a dual-cohort study
Z Zhang, P Sun, X Qian, L Zhao, T Yang, L Liu, X Xu, H Qin, Q Yang, X ZhouAbstract
Background
Non-ischemic acute myocardial injury (NI-AMInj) carries substantial long-term mortality, yet no evidence-based pharmacotherapy exists. Statins possess pleiotropic anti-inflammatory, antioxidant, and endothelial-protective properties beyond lipid lowering, but their role in NI-AMInj remains unknown.
Purpose
To evaluate the association between in-hospital statin initiation and 1-year all-cause and cause-specific mortality in NI-AMInj patients, and to explore the influence of statin type, intensity, and timing.
Methods
This retrospective cohort study included NI-AMInj patients from a regional multi-center platform (development cohort, 2013–2022) and a critical care database (external validation, 2008–2022). Patients with prior statin use were excluded from the development cohort. The exposure was in-hospital statin initiation. The primary outcome was 1-year all-cause mortality; secondary outcomes included cardiovascular and non-cardiovascular death. Multivariable Cox regression models with stepwise covariate adjustment were used. Sensitivity analyses included propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and exclusion of early deaths and high-risk subgroups.
Results
The development cohort included 50,670 statin-naive patients (statin group: 25,135; non-statin group: 25,535; 1-year mortality: 11.5% vs 27.5%). The external validation cohort included 10,893 patients (statin: 5,819; non-statin: 5,074; 1-year mortality: 29.1% vs 41.1%). In fully adjusted models, statin use was independently associated with lower 1-year all-cause mortality in both cohorts (development: HR 0.79, 95% CI 0.75–0.84; validation: HR 0.75, 95% CI 0.69–0.80; both P<0.001). In the development cohort, statin use was also associated with reduced cardiovascular death (HR 0.89, 95% CI 0.82–0.96), non-cardiovascular death (HR 0.66, 95% CI 0.61–0.72), cancer-related death (HR 0.63, 95% CI 0.51–0.79), and respiratory death (HR 0.59, 95% CI 0.51–0.69). The benefit was consistent across different statin types (class effect). Moderate-to-high intensity therapy showed the clearest benefit. Both early (≤48h) and late (>48h) initiation were associated with significant mortality reduction. Subgroup analyses showed no significant interaction by sex, diabetes, coronary artery disease, or baseline LDL-C level. Sensitivity analyses confirmed the robustness of the findings.
Conclusions
In-hospital statin therapy is independently associated with significantly lower 1-year all-cause and cause-specific mortality in NI-AMInj patients across different populations and healthcare settings. The benefit extends beyond cardiovascular death, exhibits a class effect across statin types, and persists regardless of initiation timing. These findings support consideration of statin therapy in NI-AMInj, a population currently lacking specific pharmacological recommendations.Association of Statin Use with Mortality Risk