BackgroundThe role of angiotensin II receptor blockers (ARBs) in migraine prophylaxis varies globally, partly due to insufficient evidence from randomized controlled trials (RCTs) supporting their efficacy. We aimed to conduct a systematic review and meta-analysis of ARBs in migraine prophylaxis.MethodsWe searched PubMed/MEDLINE, Embase, Cochrane, Google Scholar, Clinicaltrials.gov, ITCRP, and EudraCT from database inception to 22 September 2025. The searches were conducted between 19 and 22 September 2025 for controlled trials comparing any ARB to placebo or other preventive migraine drugs in individuals with episodic or chronic migraine. Guidelines, letters, editorials, narrative reviews, case reports, and news were excluded. Summary data were extracted by two reviewers, and random-effects meta-analyses were performed, with heterogeneity assessed using Cochrane I2 statistic. Primary outcomes were monthly headache/migraine days or attacks, and response rates. Adverse event occurrence was also assessed. The risk of bias was assessed using the Cochrane RoB2 tool and the certainty of evidence was assessed using GRADEpro. The study was pre-registered in Prospero (CRD42023405372) and received no funding.ResultsFour trials published between 2003 and 2025 were included in the meta-analysis: three RCTs on candesartan, and one on telmisartan. All four studies reported the outcomes migraine days and responder (≥50% reduction of migraine days) rates, and three reported headache days. A total of 659 participants were included in the meta-analysis. The combined effect size for migraine days and headache days were reductions of -1.00 (95% CI: -1.51 to -0.49, p<0.001), and -1.21 (95% CI: -1.62 to -0.81, p<0.001) days per month from baseline respectively. The odds ratio for being a responder was 2.68 (95% CI: 1.91 to 3.78, p<0.001). The certainty of evidence was low for migraine days, moderate for responder rates and high for headache days, with heterogeneity between studies categorized as 'might not be important' and no serious risk of bias.DiscussionThe systematic review and meta-analysis provide robust evidence on the effect of ARBs, particularly candesartan, in prevention of episodic migraine, supporting the rationale for reconsidering its position in international guidelines.Trial RegistrationProspero CRD42023405372.
Keywords: angiotensin II receptor blockers; candesartan; migraine prophylaxis; telmisartan.