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. 2025 Sep 16:16:1630732.
doi: 10.3389/fneur.2025.1630732. eCollection 2025.

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   2 , Faraidoon Haghdoost #  1 , Leo Davies  2 , Dennis Cordato  3 , Lyn Griffiths  4 , Grace Balicki  1 , Qiang Li  1 , Ruth Freed  1 , Craig S Anderson  1   2   5 , Alessandro S Zagami  6   7 , Candice Delcourt  1   8 , Anthony Rodgers  1
Affiliations

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 et al. Front Neurol. .

Abstract

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.

Methods: A double-blind, randomized, pilot trial in participants with episodic migraine to assess feasibility 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 randomized, mean age was 49 years, 83% female, baseline migraine frequency was 67 h, 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.

Conclusion: 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.

Clinical trial registration: ACTRN12616000937415, https://anzctr.org.au/.

Keywords: antihypertensive treatment; feasibility; migraine; randomized trials; tolerability.

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Conflict of interest statement

Griffiths reports migraine research funding from the Australian National Health and Medical Research Council (NHMRC-APP1122387), US Migraine Research Foundation, US Dept. of Defence and Teva. Zagami is an associate editor for Cephalalgia. George Health Enterprises, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin and blood pressure lowering drugs; and has submitted patents for low-dose blood pressure combinations, on which Rodgers is listed as one of the inventors. Rodgers is seconded part-time to George Medicines Pty Ltd. (GM) which is developing a low-dose blood pressure lowering combination for FDA approval. The George Institute has an institutional interest to declare with respect to George Health Enterprises. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor NR declared a past co-authorship/collaboration FH with the author(s). The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Study design. *The results for the cholesterol lowering arm will be reported separately.
Figure 2
Figure 2
Consort diagram.
See this image and copyright information in PMC

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