Real world effectiveness and tolerability of candesartan in the treatment of migraine: a retrospective cohort study

Abstract

To date, two randomized, controlled studies support the use of candesartan for migraine prophylaxis but with limited external validity. We aim to evaluate the effectiveness and tolerability of candesartan in clinical practice and to explore predictors of patient response. Retrospective cohort study including all patients with migraine who received candesartan between April 2008-February 2019. The primary endpoint was the number of monthly headache days during weeks 8–12 of treatment compared to baseline. Additionally, we evaluated the frequency during weeks 20–24. We analysed the percentage of patients with 50% and 75% response rates and the retention rates after three and 6 months of treatment. 120/4121 patients were eligible, aged 45.9 [11.5]; 100 (83.3%) female. Eighty-four patients (70%) had chronic migraine and 53 (42.7%) had medication-overuse headache. The median number of prior prophylactics was 3 (Inter-quartile range 2–5). At baseline, patients had 20.5 ± 8.5 headache days per month, decreasing 4.3 ± 8.4 days by 3 months (weeks 12–16) and by 4.7 ± 8.7 days by 6 months (paired Student’s t-test, p < 0.001). The percentage of patients with a 50% response was 32.5% at 3 months and 31.7% at 6 months, while the retention rate was 85.0% and 58.3%. The number of prior treatments (Odds ratio 0.79, 95% CI 0.64–0.97) and the presence of daily headache (Odds ratio 0.39, 95% CI 0.16–0.97) were associated with a lower probability of response. Candesartan showed beneficial effects in the preventive treatment of migraine in clinical practice, including patients with chronic migraine, medication-overuse headache and resistance to prior prophylactics.

CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine

“…This shows realistic and transparent results, which are not that different from those observed in other "old" oral preventive drugs, such as amitriptyline (20), flunarizine (21), and topiramate (22), where the absolute difference of patients who achieved a 50% response rate in monthly migraine days, compared to placebo, was 16.5% higher following amitriptyline and 16.8% higher following topiramate. The proportion of patients who discontinued candesartan due to inadequate tolerability was 17.4%, which is higher than observed in the first RCT (10%) (8), and similar to what was reported in the retrospective cohort study (18.3%) (11). The proportion of patients who reported at least one TEAE was 35%, which is between that observed in the first RCT (46%) (8) and the second RCT (30%) (9).…”

“…Regarding effectiveness, assessed as the 50% response rate in HDM, this study's results, where 35-47% of patients achieved a reduction of at least 50% in the number of HDM from baseline to weeks 8-12 or 20-24, were similar to those of the two RCTs -31.6% and 43% (8,9), and to those of the retrospective cohort study -32.5% (11). The lack of a placebo control group represents a significant limitation, since some patients could have responded by chance.…”

“…Evidence for the use of candesartan for chronic migraine (CM) or treatment-resistant migraine patients came from two observational studies (10,11). The first one retrospectively evaluated patients treated between 2015 and 2018.…”

“…The study showed that 44% of patients showed some degree of response, defined as a reduction in the number of headache days, migraine days, or the severity of migraine attacks (10). Another retrospective cohort study was conducted between 2008 and 2019 (11). This study included 120 patients, 70% of them with CM at baseline, with a mean number of 3.7 prior preventive drugs.…”

Pharmacogenetics in Primary Headache Disorders

“…Angiotensin II receptor antagonists (or blockers, ARBs, candesartan) ( Stovner et al, 2014 ; Sánchez-Rodríguez et al, 2021 ) and ACE inhibitors (lisinopril) can be used for the preventive treatment of migraine ( Loder et al, 2012 ; Stovner et al, 2014 ; Steiner et al, 2019 ; Sánchez-Rodríguez et al, 2021 ). The main mechanism of action of ARBs is the blockade of angiotensin II type 1 (ATII) receptors, whereas the main mechanism of ACE inhibitors is the blockade of angiotensin I conversion to angiotensin II.…”