Efficacy of angiotensin II receptor antagonists in preventing headache: a systematic overview and meta-analysis

Purpose To determine whether angiotensin II receptor antagonists prevent headaches. Methods We systematically searched MEDLINE, EMBASE, the Cochrane Library, and International Pharmaceutical Abstracts for studies in which participants were randomly assigned to an angiotensin II receptor antagonist or placebo. We also contacted experts and manually reviewed all references to identify additional articles. Two reviewers independently extracted data from the studies. Discrepancies were resolved by discussion. We estimated the pooled relative risk (RR) for headache using the random-effects model and examined dose response using random-effects Bayesian logistic regression. Results Data from 27 studies involving 12,110 patients were included in the meta-analysis. The risk of headache was about one third lower in patients taking an angiotensin II receptor antagonist than in those taking placebo (RR = 0.69; 95% confidence interval [CI]: 0.62 to 0.76; the test of heterogeneity was negative, P = 0.2). The odds ratio for having a headache per unit dose of the reference drug losartan was 0.81 (95% CI: 0.68 to 0.93). Conclusion Angiotensin II receptor antagonists appear to be effective in preventing headaches, but the mechanism of this benefit and the types of headaches that are prevented are not known. Randomized trials are warranted.