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DRUG INFORMATION ROUNDS

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

Professor, Department of Pharmacy Practice, College of Pharmacy, Southwestern Oklahoma State University; Department of Pharmacy, Integris Baptist Medical Center, Oklahoma City, OK

Emilee K Bailey, PharmD

Staff Pharmacist, Salisbury Pharmacy and Integris Clinton Regional Hospital, Clinton, OK

Ashley N Reed, PharmD

Staff Pharmacist, Wal-Mart Pharmacy, Wellington, KS

Mark A Gales, PharmD BCPS

Professor, Department of Pharmacy Practice, College of Pharmacy, Southwestern Oklahoma State University

Reprints: Dr. B Gales, Department of Pharmacy, Integris Baptist Medical Center, 3300 NW Expressway, Oklahoma City, OK 73112, fax 405/951-8274, barry.gales{at}swosu.edu

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, renin-angiotensin 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 < 0.05). 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.

Key Words: angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, headaches, migraine, renin-angiotensin system

Published Online, January 19, 2010. www.theannals.com, DOI 10.1345/aph.1M312