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 PR o FESS ( N  =   20 332) and ESPS 2 ( N  =   6602) trials. Hazard ratios ( HR s) for recurrent stroke were calculated using the C ox model. Results In PR o FESS , 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 ESPS 2, 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 PR o FESS 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 ESPS 2 suggest that dipyridamole‐induced headache may reflect better cerebrovascular function.