Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis

Background and purpose Our objective was to investigate the association between recurrent stroke risk and headache induced by extended‐release dipyridamole (ER‐DP) when administered alone or with low‐dose aspirin (ASA+ER‐DP). Methods This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20 332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. Results In PRoFESS, the 2.5‐year recurrent stroke risk in patients receiving ASA+ER‐DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73–0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER‐DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35–0.77; P = 0.001). No such difference was observed in clopidogrel‐treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER‐DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31–1.27; P = 0.19) and 7.3% in patients who discontinued ER‐DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27–1.04; P = 0.06). Conclusions Patients taking ASA+ER‐DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non‐significant) findings for ASA+ER‐DP and ER‐DP in ESPS2 suggest that dipyridamole‐induced headache may reflect better cerebrovascular function.