New trial data supports candesartan as a “compelling option” for migraine prevention, prompting researchers to call for its inclusion as a first-line treatment in international guidelines.
According to the research team, the observed efficacy of candesartan in the trial “appears consistent” with that of other preventive treatments, including calcitonin gene-related peptide monoclonal antibodies (CGRP).
“Given its demonstrated efficacy, high tolerability, low toxicity, ease of administration, and affordability, candesartan should be included in migraine prevention guidelines as a first-line treatment,” they said.
The phase 2 trial took place at nine hospitals across Norway and one large hospital in Estonia. Participants aged 18 to 64 were randomised to receive oral candesartan 16 mg (n=156), candesartan 8 mg (n=150) or a placebo (n=151) daily for 12 weeks.
During the baseline period, all groups reported a mean of 5.7 migraine days and 8.3 headache days per four-week interval.
By weeks 9-12, the reduction in migraine days was 2.04 days in the candesartan 16 mg group compared with 0.82 days in the placebo group (difference between groups -1·22; p<0·0001).
The proportion of participants experiencing a 50% or greater reduction in monthly migraine days was 49% in the 16 mg candesartan group compared with 28% in the placebo group.
Participants receiving candesartan 8 mg also experienced significant changes in mean monthly migraine days (mean change –2·20 days; p<0·0001), according to the paper, published in The Lancet Neurology [link here].
“The trial demonstrates that daily administration of candesartan 16 mg over 12 weeks is both effective and well-tolerated in individuals with episodic migraine,” the authors noted.
“Efficacy was also observed with candesartan 8 mg indicating that a lower dose might be sufficient for responsive patients,” they added.
Common adverse effects in all three trial groups included dizziness, respiratory tract infection, nausea and tiredness. Most adverse events were characterised by investigators as mild, with no imbalance in the incidence of moderate or severe events amongst the three trial groups.
In a linked editorial [link here], Dr Mi Ji Lee, Assistant Professor of Neurology at Seoul National University College of Medicine, said the findings could widen the scope for first-line therapies for migraine, which have recently focused on new migraine-specific preventive agents such as CGRPs and gepants.
Candesartan is a potential alternative or add-on treatment, the editorial argued, when CGRP-targeted therapies are “contraindicated or yield suboptimal responses.”
Although two previous RCTs evaluated candesartan’s efficacy in migraine prevention, the earlier studies were small, single-centre trials designed before the current standard of diagnosis and clinical trials for episodic and chronic migraine, Professor Lee noted. As a result, most guidelines have only weakly recommended candesartan.
“This study strengthens the evidence for angiotensin II receptor antagonists in migraine prevention and could prompt reconsideration of candesartan’s place in international guidelines,” she added.