Angiotensin receptor blockers (ARBs), particularly candesartan, may help to reduce the frequency of episodic migraine, according to a new meta-analysis of recent studies.

Researchers looked at pooled results of four studies and found a significant reduction in headache days, with certainty rated as high for this outcome in the analysis.

The findings also showed a strong association with responder rates, with moderate certainty.

Although the meta-analysis also demonstrated significant reductions in migraine days, the certainty for this evidence was rated as low by the investigators.

“The systematic review and meta-analysis provide robust evidence on the effect of ARBs, particularly candesartan, in prevention of episodic migraine, supporting the rationale for reconsidering its position in international guidelines,” the authors said.

The study looked at four randomised controlled trials published between 2003 and 2025, three comparing candesartan and placebo and one comparing telmisartan and placebo. 

The trials had a total of 659 participants (575 from the candesartan studies and 84 from the telmisartan study), most with episodic migraine. Between 79% and 85.6% of participants were female, and one of the four studies included a single participant with chronic migraine.

A total of 459 participants receiving an ARB and 313 receiving placebo were included in the meta-analysis on change in monthly migraine days. A reduction in migraine days from baseline occurred in the intervention group across all four studies, with a pooled mean reduction of 1.00 day per month compared with placebo (p<0.001).

The three studies evaluating candesartan also reported data on headache days, while the telmisartan study did not, listing it instead as a secondary outcome. 

The meta-analysis of headache days included 419 patients receiving candesartan and 269 receiving placebo, with a reduction of 1.21 (p<0.001) headache days per month from baseline in the intervention group.

All four studies found a higher responder rate on candesartan or telmisartan than on placebo, with a combined effect odds ratio of 2.68 (p<0.001).

Three of the four studies reported the number of participants who had experienced an adverse event (AE) since the last visit, suggesting a 10% higher risk of AEs with candesartan and telmisartan compared to placebo, although the estimate was based on limited data.

“Dizziness, fatigue and paresthesia were consistently reported across the candesartan trials and may be particularly relevant in a migraine population already vulnerable to central nervous system symptoms,” the authors observed.

NICE is currently appraising candesartan for migraine prevention, although its existing migraine recommendations don’t recommend the drug. The British Association for the Study of Headache (BASH) does, however, recommend candesartan for migraine prevention.

Study variations noted

The authors also highlighted variations in the included studies. 

The telmisartan study was a multicentre, parallel-group German trial comparing 80 mg of telmisartan with a placebo. The researchers pointed to a “high risk of bias” in this trial but noted that its contribution of data to the pooled estimates was generally low.

Two Norwegian studies compared 16 mg of candesartan with placebo, with one of the studies including a third treatment arm with propranolol. 

The third candesartan study was a three-arm parallel group Norwegian RCT in which participants received placebo, 8 mg or 16 mg of candesartan, with the comparison of 16 mg and placebo constituting the primary endpoint.

Definitions of a migraine day also varied across the studies.

The authors noted that the efficacy of other ARBs, including valsartan, and telmisartan, remains unclear given the paucity and low quality of available data. 

They also highlighted other review limitations. Because only one participant with chronic migraine was included, they acknowledged the evidence of ARBs as a preventive treatment in this patient group is “currently limited to observational studies”.

In addition, although the combination of different ARBs in the meta-analysis could limit its interpretability, they noted that “additional analyses restricted to candesartan only revealed consistent results.”

The full findings are published in Cephalalgia [link here].