Statin Intolerance, Treatment Gaps, and Cardiovascular Outcomes: A 24‐Year Health System Analysis

BACKGROUND: Statin intolerance may disrupt lipid-lowering therapy (LLT). We characterized clinician-documented intolerance and assessed whether cardiovascular risk was concentrated among patients who discontinued all LLT. METHODS: We studied new statin users at Mass General Brigham using medication records dated 1987 through November 2025. Temporal trend analyses were restricted to 2001 through 2024. We characterized postintolerance management and examined cardiovascular outcomes using time-varying Cox models. Within the intolerance cohort, we compared patients who discontinued all LLT with those who continued any LLT. RESULTS: Among 254 035 new statin users, 10 644 (4.2%) developed documented intolerance after a median of 3.1 years. Musculoskeletal symptoms were documented in 68.1%. Within 90 days, 39.9% discontinued all LLT and fewer than 10% received a nonstatin-based strategy. At 3 to 6 months, mean low-density lipoprotein cholesterol increased by 6.8 mg/dL among discontinuers and decreased by 4.9 mg/dL among continuers. Compared with statin-tolerant patients, intolerance was associated with higher risks of coronary artery bypass grafting, percutaneous coronary intervention, myocardial infarction, and ischemic stroke (hazard ratios, 1.12-1.55). Within the intolerance cohort, discontinuing all LLT was associated with higher risk across all outcomes, with hazard ratios ranging from 1.38 for mortality to 2.14 for venous thromboembolism. CONCLUSIONS: Clinician-documented statin intolerance was frequently followed by complete LLT discontinuation and limited use of nonstatin therapy. Complete discontinuation identified a high-risk subgroup with worsening lipid trajectories, supporting systematic reassessment and restoration of statin or nonstatin therapy.