Effects of Add‐On Icosapent Ethyl With Standard Treatment on Functional Outcomes and Inflammatory Biomarkers in Acute Ischemic Stroke: A Blinded Randomized Controlled Trial

BACKGROUND: Ischemic stroke, a major cause of mortality and long-term disability, results from the abrupt cessation of cerebral blood flow due to vascular occlusion or rupture. Icosapent Ethyl (EPA-EE), approved for hypertriglyceridemia, has anti-inflammatory and antithrombotic properties that may lessen ischemic damage. OBJECTIVES: This trial evaluates the impact of EPA-EE on functional recovery and inflammatory markers in patients with acute ischemic stroke. METHODS: In a blinded, randomized controlled trial (RCT), adults (≥ 18 years) with acute ischemic stroke were assigned to receive either 2000 mg/day EPA-EE (EPA group) or a matched placebo alongside standard treatment for 12 weeks. Functional outcomes were measured using the modified Rankin scale (mRS) and national institutes of health stroke scale (NIHSS), while inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP), were assessed at baseline and at the 7th day. RESULTS: Of 178 patients screened, 90 were randomized, and 80 completed the 12-week intervention. The EPA group showed significantly greater functional improvement, with mean mRS score reductions of 2.18 ± 0.61 compared to 1.38 ± 0.66 in the placebo group (p = 0.001) and NIHSS score reductions of 5.00 ± 1.83 versus 3.38 ± 1.38 (p = 0.001). IL-6 levels decreased by 6.32 ± 5.69 pg/mL in the EPA group compared to 2.95 ± 4.11 pg/mL in the placebo group (p = 0.003). Changes in CRP levels were not statistically significant (p = 0.142). EPA-EE at 2000 mg/day was well tolerated, with no serious adverse events reported. CONCLUSION: EPA-EE administration significantly improves functional outcomes and reduces IL-6 levels in patients with acute ischemic stroke, suggesting its potential as an effective add-on therapy. TRIAL REGISTRATION: CLINICALTRIALS. GOV IDENTIFIER: IRCT20170608034390N15.