title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 < or = 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.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, Southwestern Oklahoma State University, Oklahoma City, OK, USA. barry.gales@swosu.edu
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Gales
authors.forename: Emilee K
authors.initials: EK
authors.lastname: Bailey
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Reed
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gales
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic; D006801:Humans; D017706:Lisinopril / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; C081643:candesartan