Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for the Prevention of Migraines

Abstract

Objective: To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis. Data Sources: MEDLINE (1966–October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renina-ngiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes. Study Selection and Data Extraction: English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources. Data Synthesis: Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo In the controlled trial (p < 0.06). Clinically significant (>50%) reductions in migraine measures were more common (52–66%) in open-label ACE inhibitor trials than in the controlled (32–36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p ≤ 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54–88%) in open-label ARB trials than in the controlled (26–38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy. Conclusions: ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.