US Headache Study

Acetaminophen in the Treatment of Headaches Associated with Dipyridamole-ASA Combination

Background and purpose

The fixed dose combination of extended-release dipyridamole plus ASA (DAC, Aggrenox®) has proven efficacy in the secondary prevention of stroke. Headaches are a well-known adverse effect of treatment with dipyridamole. In the Second European Stroke Prevention Study (ESPS 2), discontinuation due to headache was four times more likely among participants treated with dipyridamole, even though the rates were modest in the dipyridamole and in the placebo plus aspirin arms (8.0% vs. 2.1%). Patterns of DAC-associated headache and potential treatments for these headaches have not been assessed. Acetaminophen is approved by the Food and Drug Administration for marketing in the United States as a non-prescription drug for temporary relief of headache and other aches and pains, and has demonstrated efficacy in treating the pain of migraine and tension-type headache. Because headache is a frequent adverse effect of DAC, we aimed in this study 1) to assess the frequency and severity of headache following DAC use in an older population and 2) to assess the efficacy of acetaminophen 1,000 mg vs. placebo in the acute and preemptive treatment of headaches associated with DAC.