Preventing Migraine with an ARB?

Summarized by Robert W. Griffith, MD
February 21, 2003

Introduction

Migraine affects about 240 million people, worldwide, and is one of the most disabling disorders, albeit not continuously. The newer triptan drugs can prevent attacks in 50% to 60% of subjects, although there is often only partial relief. Prophylaxis is indicated if there are 2 or more attacks a month.

The angiotensin-converting enzyme (ACE) inhibitor lisinopril has been reported to be an effective prophylactic agent for migraine. It seemed appropriate for Norwegian investigators to see if an angiotensin II receptor blocker (ARB) would have the same effect. They have reported the results of such a study in JAMA.

Method

This was a randomized, double-blind, placebo-controlled, crossover study done at a single neurological outpatient clinic in Norway. Participants were recruited by newspaper advertisements. To be included, patients had to have 2 to 6 migraine attacks a month for at least a year, and that started before they were 50 years old. The usual exclusion criteria applied; in addition, use of daily migraine prophylaxis in the 12 weeks before the study, and having used more than one prophylactic drug before the study, were reasons for exclusion.

All the participants were given placebo for 4 weeks to verify the frequency of migraines. They were then allocated at random to receive either the ARB, (candesartan16 mg daily), or matching placebo. After 12 weeks, the participants were taken off medication for 4 weeks, and then prescribed the alternative medication - placebo or candesartan - for another 12 weeks.

The subjects kept headache diaries, with details of duration, severity, level of disability, nausea, vomiting, photophobia, acute medications used, days of sick leave, and adverse events. At enrollment, at randomization, and after each 12-week treatment period, subjects were examined by a physician, and had additional blood pressure readings and blood sampling 2 weeks after the start of each treatment period.

The primary endpoint measure was determined to be the number of days with headache; secondary endpoints included hours with headache, days with migraine, headache severity index, level of disability, and doses of triptans and analgesics.

Results

Sixty subjects were randomized to receive first either candesartan or placebo. After the washout period, 57 were given the alternative medication. Dropouts were for various reasons, but occurred equally on either type of medication. The intent-to-treat analysis (ITT) was done on 57 patients (45 women, 12 men).

In the ITT analysis, the mean number of days with headache was 18.5 with placebo compared with 13.6 with candesartan (p=0.001). Hours with headache, migraine days, migraine hours, headache severity index, and disability level were all reduced with candesartan, compared with placebo (p<0.001). Relative reductions in these variables with candesartan, compared with placebo, ranged from 26% to 36%. Compared with the baseline run-in period, the reductions with candesartan ranged from 46% to 54%.

Mean blood pressures during the treatment periods were 126/77 mmHg for placebo, and 115/70 mmHg for candesartan (p<0.001). There were no significant differences in adverse events reported during the candesartan and placebo treatment periods.

Comment

Several classes of antihypertensives have been established as potential prophylactic agents for migraine - beta-blockers, calcium channel blockers, and more recently ACE inhibitors. The anticonvulsant valproic acid is another drug that has shown benefits in prophylaxis. It's tempting to see a connection between the efficacy of ACE inhibitors and the ARB tested in this study, but it's more likely that factors other than the angiotensin receptor play a major role. Until more is known, we can add the ARB candesartan to the growing list of agents that may be used with hope of success in preventing migraine attacks.

Source

• Prophylactic treatment of migraine with an angiotensin II receptor blocker. A randomized controlled trial. E. Tronvik, LJ. Stovner, G. Helde,  et al., JAMA, 2003, vol. 289, pp. 65--69

Related Links
Cyberounds: Giant Cell Arteritis
Headaches in the Elderly
Disease Digest: Migraine Headaches

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