Association between long-term statin treatment intensity and major adverse cardiovascular events in patients with angiographically confirmed nonobstructive coronary artery disease

The prognostic relevance of long-term statin treatment intensity in patients with angiographically confirmed nonobstructive coronary artery disease (NOCAD) remains incompletely defined. We evaluated whether sustained moderate-to-high-intensity statin therapy was associated with major adverse cardiovascular events (MACE) in this population. This single-center retrospective cohort study screened consecutive adults who underwent coronary angiography at our hospital between 10 May 2023 and 15 May 2025. Eligible patients had a final diagnosis of angiographically confirmed NOCAD. Follow-up began on the date of coronary angiography. Follow-up ended at first MACE, loss to follow-up, or administrative censoring in May 2026, whichever came first. Statin exposure was classified at a 12-month landmark from the predominant prescribed intensity and medication coverage recorded during the first 12 months. The primary comparison was low-intensity/irregular statin therapy versus moderate-to-high-intensity statin therapy. The primary endpoint was first MACE, defined as cardiovascular death, nonfatal myocardial infarction, ischemic stroke, ischemia-driven revascularization, unstable angina rehospitalization, or heart failure rehospitalization. For the primary time-to-event analysis, risk time began at the 12-month landmark. Among 206 eligible participants, median follow-up from index angiography was 24.90 months (IQR 17.85–30.95), and 38 first MACE events (18.4%) occurred. Ninety-six patients received low-intensity/irregular statin therapy, and 110 received moderate-to-high-intensity statin therapy. In the reduced 12-month landmark Cox model, moderate-to-high-intensity statin therapy was associated with a lower observed hazard of MACE (HR 0.26, 95% CI 0.12–0.56; P < 0.001). Older age, diabetes, and multi-vessel or heavier plaque burden were associated with higher MACE risk. Sensitivity analyses that adjusted for baseline LDL-C, angiography indication variables, and propensity score methods were directionally consistent with the primary analysis. Among patients with angiographically confirmed NOCAD who remained event-free through the 12-month landmark, sustained moderate-to-high-intensity statin therapy was associated with a lower subsequent observed risk of MACE. Given the retrospective, single-center, non-randomized design and the possibility of residual confounding, these findings are hypothesis-generating and do not establish a causal effect of statin intensification. Not applicable.