Prophylactic Treatment of Migraine With an Angiotensin II ReceptorBlocker

Abstract

ContextThere is a paucity of effective, well-tolerated drugs available for migraine prophylaxis.Objective To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug.Design and Setting Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002.Patients Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements.Interventions A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan. Main Outcome MeasuresThe primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire. ResultsIn a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (P=.001) in the intention-to-treat analysis (n=57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95; PϽ.001), days with migraine (12.6 vs 9.0; PϽ.001), hours with migraine (92.2 vs 59.4; PϽ.001), headache severity index (293 vs 191; PϽ.001), level of disability (20.6 vs 14.1; PϽ.001) and days of sick leave (3.9 vs 1.4; P=.01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of Ն50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods. ConclusionIn this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.

A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study

“…Overall, CAN was different from PLA and similar to PRO with regard to general questions about AEs or other illnesses, level of discomfort due to AEs (Table 5), and number of free-text AEs (Table 2). Hence, we conclude that the previous contention that CAN has an AE profile similar to PLA in migraine patients (6) was not confirmed in the present study. It does seem, however, that AE profiles differ between CAN and PRO (Table 2).…”

Superior outcomes of candesartan over topiramate in the treatment of migraine: A comparative cohort study

“…All in all, this study indicates that treatment guidelines and reimbursementprotocols should be revised to prioritize trying candesartan, without the requirement to also try topiramate, before anti-CGRP monoclonal antibodies can be tried. The findings of our study are consistent with two small crossover trials that compared candesartan to placebo and propranolol, 6,7 as well as with two retrospective cohort studies conducted in patients with chronic migraine (CM). 9,10 Another relevant study, the CandeSpartan trial, included patients with CM and medication overuse headache (MOH), thus representing a more severely affected population.…”

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

“…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). In addition, the tolerability profile was quite unique and not that different from that observed in the more novel preventive drugs (23).…”

“…In the present study, half of the enrolled patients had MOH, almost half had CM, 74% were severely impacted by migraine, and 32% of patients fulfilled criteria for treatment-resistant migraine (15). In this “more difficult” to treat population, both effectiveness and tolerability were in line with prior studies (8–11).…”