title: Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: G
authors.initials: G
authors.lastname: Davidai
authors.forename: D
authors.initials: D
authors.lastname: Cotton
authors.forename: P
authors.initials: P
authors.lastname: Gorelick
authors.forename: P M W
authors.initials: PM
authors.lastname: Bath
authors.forename: R B
authors.initials: RB
authors.lastname: Lipton
authors.forename: R
authors.initials: R
authors.lastname: Sacco
authors.forename: H-C
authors.initials: HC
authors.lastname: Diener
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D004176:Dipyridamole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012008:Recurrence; D012306:Risk; D055502:Secondary Prevention; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D001241:Aspirin
keywords: cerebrovascular disease; dipyridamole; headache; intracerebral hemorrhage; stroke; stroke prevention