Blood pressure lowering for prevention of episodic migraine: results of a pilot randomized, placebo-controlled trial of combination blood pressure lowering medication with propranolol

Cheryl Carcel^1*Faraidoon Haghdoost¹Leo Davies²Dennis John Cordato³Lyn R Griffiths⁴Grace Balicki¹Qiang Li¹Ruth Freed¹Craig S Anderson¹ALESSANDRO ZAGAMI⁵Candice Delcourt¹Anthony Rodgers¹

• ¹George Institute for Global Health, University of New South Wales, Newtown, Australia
• ²Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia, Sydney, Australia
• ³Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Sydney, Australia
• ⁴Centre for Genomics and Personalised Health, Queensland University of Technology, Queensland, Australia
• ⁵Institute of Neurological Sciences, Prince of Wales Hospital, Sydney, Australia

Background: Beta blockers are effective in migraine prevention. Low-dose combination therapy of blood pressure lowering is likely to lower blood pressure more than a beta-blocker, but there are no data on comparative efficacy of these treatments in migraine prophylaxis.A double-blind, randomized, pilot trial in participants with episodic migraine to assess feasibility, efficacy and tolerability of low-dose triple combination BP lowering (telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) vs propranolol 160 mg daily vs matching placebos. The primary outcome was monthly headache days.Results: Between March 2017 and June 2018, 378 participants were screened and 30 were randomized (8%). The key reasons for ineligibility among screen failures were low blood pressure (86, 26%), unwilling to participate in a drug trial (76, 23%) and not meeting episodic migraine criteria (54, 16%). Among those randomised, mean age was 49 years, 83% female, baseline migraine frequency was 67 hours, aura present in 47%, mean baseline BP was 131/87 mmHg. As expected from a small pilot, the confidence intervals for treatment effect estimates were wide: reduction in monthly headache days for the low-dose triple were -0.6 (95% confidence interval [CI] -2.9, 1.8) and for propranolol -1.1 (95% CI -3.8, 1.6) compared to placebo. Tolerability was good, there were no dropouts from adverse events.As a pilot study, the trial was not powered to detect efficacy; larger trials are required to determine the effect of low-dose triple combination blood pressure lowering on migraine. The medication was safe and well tolerated by participants with migraine; it is likely that study co-design with people with lived experience of migraine will benefit recruitment into the trial.