Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial

**Background:** Intensive LDL cholesterol reduction is recommended for patients with coronary artery disease, and statins are the cornerstone of therapy. Rosuvastatin and atorvastatin are the two most potent statins, but few randomized trials have directly compared their long-term clinical outcomes and safety. The LODESTAR trial provided an opportunity to compare these two statins in a large cohort.

**Methods:** This was a secondary analysis of the LODESTAR trial, a randomized, open-label, multicenter trial conducted at 12 hospitals in South Korea from September 2016 to November 2019. A total of 4400 adults (age ≥19 years) with coronary artery disease were randomly assigned to rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomization. The primary outcome was a three-year composite of all-cause death, myocardial infarction, stroke, or any coronary revascularization. Secondary outcomes included new-onset diabetes mellitus, cataract surgery, and other safety endpoints. Mean age was 65 years, 27.9% were women, 33.4% had diabetes, and 55.8% had prior PCI. Follow-up visits occurred at 6 weeks, 3, 6, 12, 24, and 36 months.

**Key Results:** 4341 participants (98.7%) completed the trial. The mean daily dose at three years was 17.1 mg (SD 5.2) in the rosuvastatin group and 36.0 mg (SD 12.8) in the atorvastatin group (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% CI 0.86 to 1.30; P=0.58). Mean LDL cholesterol during treatment was 1.8 mmol/L (SD 0.5) in the rosuvastatin group and 1.9 mmol/L (SD 0.5) in the atorvastatin group (P<0.001). Rosuvastatin was associated with a higher incidence of new-onset diabetes mellitus requiring initiation of antidiabetics (7.2% vs 5.3%; HR 1.39, 95% CI 1.03 to 1.87; P=0.03) and cataract surgery (2.5% vs 1.5%; HR 1.66, 95% CI 1.07 to 2.58; P=0.02). Other safety endpoints did not differ significantly between groups.

**Clinical Implications:** Rosuvastatin and atorvastatin showed comparable efficacy for the composite cardiovascular outcome over three years in patients with coronary artery disease. Despite achieving lower LDL cholesterol levels, rosuvastatin did not translate into a reduction in clinical events and was associated with a higher risk of new-onset diabetes and cataract surgery. These findings suggest that when choosing between these two potent statins, clinicians should consider not only LDL-lowering efficacy but also the potential for adverse effects, particularly in patients at risk for diabetes or cataracts. The results support individualized statin selection and highlight the need for monitoring glucose metabolism and cataract development in patients on rosuvastatin.