A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study

Abstract

Objective The objective of this article is to see whether the effect of candesartan for migraine prevention, shown in one previous study, could be confirmed in a new study, and if so, whether the effect was comparable to that of propranolol (non-inferiority analysis), and whether adverse events were different. Methods In a randomised, triple-blind, double cross-over study, 72 adult patients with episodic or chronic migraine went through three 12-week treatment periods on either candesartan 16 mg, propranolol slow-release 160 mg, or placebo. The main outcome measures were days with migraine headache per four weeks (primary outcome), days with headache, hours with headache, proportion of responders (>50% reduction of migraine days from baseline), and adverse events. Results In the modified intention-to treat-analysis, candesartan and propranolol were both superior to placebo: 2.95 (95% confidence interval: 2.35–3.55%) and 2.91 (2.36–3.45%), versus 3.53 (2.98–4.08%) for migraine days per month ( p = 0.02 for both comparisons, Wilcoxon's paired signed rank test, blinded statistical analysis). Candesartan was non-inferior to propranolol (and vice versa). The proportion of responders was significantly higher on candesartan (43%) and propranolol (40%) than on placebo (23%) ( p = 0.025 and <0.050, respectively). There were more adverse events on candesartan ( n = 133%) and propranolol ( n = 143%) than on placebo ( n = 90%), and the adverse event profiles of the active substances differed somewhat. Conclusion It is confirmed that candesartan 16 mg is effective for migraine prevention, with an effect size similar to propranolol 160 mg, and with somewhat different adverse events. Trial registration: EUDRACT (2008-002312-7), ClinicalTrials.gov (NCT00884663).