Objective.— To investigate the effect of low-intensity anticoagulation with warfarin on chronic cluster headache refractory to pharmacological management.
Background.— Isolated case reports on induction of remission in patients with intractable chronic cluster headache upon institution of oral anticoagulant therapy do exist. Nonetheless, evidence from randomized controlled trials on the role of oral anticoagulants in cluster headache is lacking.
Methods.— Thirty-four patients with refractory chronic cluster headache were randomized to receive warfarin or placebo for 12 weeks. Warfarin was administered to achieve an international normalized ratio between 1.5 and 1.9. After a washout period of 2 weeks, patients were crossed over from 1 treatment to the other. Status of cluster headache was assessed during both treatment periods. The primary outcome measure was the occurrence of remission lasting ≥4 weeks.
Results.— Seventeen (50%) patients underwent remission for ≥4 weeks during the warfarin period vs 4 (11.8%) patients during the placebo period (P = .004). This was associated with absolute risk reduction of 0.38 (95% CI = 0.18-0.58), and number needed to treat of 2.6 (95% CI = 1.7-5.5). The Kaplan–Meier curves for occurrence of remission had a hazard ratio of 5.26 (95% CI = 2.13-13.03, P = .0003). Frequency, duration, and intensity of cluster attacks were all significantly lower during treatment with warfarin (P < .01).
Conclusion.— In patients with refractory chronic cluster headache, low-intensity anticoagulation with warfarin was associated with significantly higher incidence of remission and less impact of headache on patients' lives compared with placebo.