Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the Preventative Treatment of Episodic Migraine in Adults.

PURPOSE OF REVIEW: Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with migraine. To identify gaps in research and provide guidance for future clinical trials. RECENT
FINDINGS: A search was completed using PubMed, MEDLINE, Embase, and the Cochrane Library January 1, 1990 through December 31, 2017. The following are keywords used in the search: migraine, migraine prophylaxis/prevention, renin-angiotensin-aldosterone system, RAAS, ACE inhibitors, angiotensin-converting enzyme inhibitors: quinapril, perindopril, ramipril, captopril, enalapril, lisinopril, benazepril, fosinopril. Angiotensin receptor blockers, ARB, angiotensin II receptor antagonists: candesartan cilexetil, irbesartan, olmesartan, valsartan, losartan, azilsartan medoxomil, telmisartan, and eprosartan. The search included randomized controlled trials (RCT), systemic reviews and open-label studies of ACE inhibitors and ARB for the prevention of migraine attacks in adults 18-70 years old. Of 2461 retrieved articles, 18 included RCT, meta-analysis, systemic reviews, or guidelines published on ACE inhibitors or ARB in the prevention of migraine. Three RCT with telmisartan 80 mg, candesartan 16 mg, and enalapril 10 mg, and two open-label trials with lisinopril 5 mg and ramipril 5 mg found a high number of responders with greater than 50 % reduction in migraine attack frequency when compared to a 4-week baseline period. Candesartan was superior to placebo while telmisartan and enalapril were not. Lipophilic ACE inhibitors and ARBs can be effective prophylactic agents for reduction of migraine frequency in adults. Based on the limited number of published trials and small sample size, they are not recommended as first-line prophylactic agents. However, in populations with co-morbidities such as hypertension, they may be useful as first- or second-line prophylactics. Additional trials following the International Headache Society's guidelines on RCT are warranted.