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

Eur J Neurol. 2014 Oct;21(10):1311-7. doi: 10.1111/ene.12484. Epub 2014 Jul 8.


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.

Keywords: cerebrovascular disease; dipyridamole; headache; intracerebral hemorrhage; stroke; stroke prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / therapeutic use
  • Brain Ischemia / prevention & control*
  • Delayed-Action Preparations
  • Dipyridamole / administration & dosage
  • Dipyridamole / adverse effects
  • Dipyridamole / pharmacology*
  • Drug Therapy, Combination
  • Female
  • Headache / chemically induced*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Recurrence
  • Risk
  • Secondary Prevention
  • Stroke / prevention & control*
  • Treatment Outcome


  • Delayed-Action Preparations
  • Platelet Aggregation Inhibitors
  • Dipyridamole
  • Aspirin