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

BackgroundCandesartan and topiramate are both recommended for migraine prevention, but direct comparative data remain limited.AimTo evaluate and compare the tolerability and effectiveness of candesartan versus topiramate for migraine prevention using systematically collected real-world data.MethodsThis longitudinal cohort study included patients treated at the Leiden Headache Center (LHC), with data collected using our validated E-headache diary. The 28 days preceding treatment initiation served as the baseline period. The primary endpoint was the proportion of participants that discontinued candesartan or topiramate within the 6-month follow-up. Secondary endpoints included ≥50%-response rate, change in monthly migraine days (MMD), headache days (MHD), acute medication days (MAMD), and HIT-6 from baseline to the last 28-day period with the highest achieved dosage of candesartan (ranging 4-32 mg daily) or topiramate (25-100 mg daily). Patients were assigned a propensity score based on baseline MHD, MMD, HADS, and number of failed preventive treatments. The primary analysis looked at discontinuation rates of candesartan and topiramate by using a Kaplan-Meier curve with Cox regression, adjusting for group differences by including the propensity score as a covariate. Secondary endpoint regressions were adjusted for propensity score and time to reach the highest dosage month. The primary and secondary outcomes were also investigated in a sensitivity analysis by applying optimal matching based on the propensity score.ResultsIn total 661 migraine participants were included. In the candesartan group less participants discontinued medication within 6-months follow-up compared to the topiramate group (29.7% versus 67.3%; HR 2.5 [95% CI: 1.9-3.3], p < 0.001). Candesartan had higher ≥50% response rates than topiramate (47% versus 29%, OR 0.6 [95% CI: 0.4-0.8], p = 0.004) and greater reduction in MHD (difference -1.1 days [95% CI: -2.2 to -0.01], p = 0.04). No differences were observed between treatments in reduction of MMD, MAMD, or HIT-6 scores after adjustment. These findings were confirmed in the sensitivity analysis using optimal matching.ConclusionsCandesartan demonstrates a favorable tolerability and effectiveness profile compared to topiramate. Therefore, (inter)national treatment guidelines for migraine prevention should be revised to spare patients from being prescribed medications that have a low tolerability profile, as demonstrated by this study.