Effect of atorvastatin versus no Statin Treatment on major clinical events in Acute CardioEmbolic stroke patients without a definite indication for statin therapy: protocol for the STACE trial

Background: Evidence supporting the use of statin therapy to reduce stroke recurrence and cardiovascular events in acute cardioembolic stroke (CES) patients without atherosclerosis is limited. Past observational studies have been hampered by selection bias and unmeasured confounding factors. This study aims to investigate the potential benefits of statin therapy in acute CES patients without established indications through a registry-based, randomized clinical trial. Methods: This is a registry-based, multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) study designed to evaluate the efficacy and safety of statin therapy in acute CES patients without established indications for statin use. Patients will be randomly assigned (1:1) to either statin users or non-users, with statin users receiving atorvastatin at a dose of 10 mg or higher throughout the study period. We plan to recruit 1036 participants to detect a relative risk reduction of 43% with 80% power and a two-sided alpha error of 0.05, accounting for a 10% loss to follow-up. The primary outcome is the occurrence of a major clinical event, defined as a composite of stroke recurrence, myocardial infarction, and all-cause mortality within 3 months after the index stroke. The secondary efficacy outcomes include (1) stroke recurrence, (2) all-cause mortality, (3) vascular death, and (4) major vascular events. Discussion: This study will assist stroke physicians in determining the appropriate use of statin therapy for acute CES patients who do not have guideline-based indications. Trial registration: CRIS Registration Number: KCT0006806. Registered on November 29, 2021. URL: https://cris.nih.go.kr/cris