OBJECTIVE: To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease.
DESIGN: Randomised, open label, multicentre trial.
SETTING: 12 hospitals in South Korea, September 2016 to November 2019.
PARTICIPANTS: 4400 adults (age =19 years) with coronary artery disease.
INTERVENTIONS: Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation.
MAIN OUTCOME MEASURES: The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities.
RESULTS: 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (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% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups.
CONCLUSIONS: In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02579499.
This study (LODESTAR) was a direct comparison of rosuvastatin and atorvastatin for secondary prevention in a Korean population. The study was well-randomized with intention-to-treat methodology. Both high-potency statins were equally effective in LDL reduction and event reduction over a three-year period. For side effects, the group managed with rosuvastatin had a slightly higher incidence of new onset diabetes, diabetes requiring medications, and cataracts requiring surgery, with diabetes and cataracts both known side effects of statins. Number needed to harm was 53 for diabetes requiring medication and 100 for cataract surgery, respectively. Asians have genetic differences making them more responsive to lower-dose statins. While there seems to be a slight advantage in reduced side effects for atorvastatin, this study cannot yet be applied to non-Asian populations given known genetic differences. Additional studies of similar quality in non-Asian populations are needed.