Dose titration to reduce dipyridamole-related headache.
BACKGROUND
Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance.


METHODS
This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1-28), reduced dose (placebo on days 1-4, ASA+MR-DP once daily before bed during days 5-14, and b.i.d. on days 15-28), and regular dose (placebo on days 1-4, and ASA+MR-DP b.i.d. on days 5-28). Using Chinese diary card, headache was assessed as mean cumulated headache (Sigma frequency x intensity/occurrence days x study days) over the study period, and was graded 0-4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0.


RESULTS
Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5-14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant.


CONCLUSIONS
Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.
Chang
Yeu-Jhy
YJ
Department of Neurology, Linkou Chang Gung Memorial Hospital, and Chang Gung University, College of Medicine, Taoyuan, Taiwan.
Ryu
Shan-Jin
SJ
Lee
Tsong-Hai
TH
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D004176:Dipyridamole / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015995:Prevalence; D020521:Stroke / Q000517:prevention & control*; D013624:Taiwan / Q000453:epidemiology
D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D001241:Aspirin