Abstract
In this issue of Cephalalgia, Benseñor et al. (1) report the results of a subgroup analysis of the large Women's Health Study investigating whether a low dose of acetylsalicyclic acid (ASA) 100 mg every other day has a prophylactic action in migraine. The study has a total of 453787 health professionals, 1001 of whom had a least one migraine attack and participated in the trial. 525 women were allocated to ASA and 476 to placebo. Since all the women were health professionals one can assume that they were able to diagnose migraine. This subset of the main study used headache diaries to document migraine frequency and the characteristics of migraine attacks. The study showed a trend in favour of ASA. This was true for all migraine parameters measured (frequency, severity, duration and incapacitation). The difference, however, was statistically not significant. This study was large but was performed in women beyond the age of 45. The results therefore cannot be generalized to younger women.
As early as 1977, O'Neill and Mann (2), in a small open trial, observed that daily treatment with 1300 mg of ASA reduced the frequency of migraine attacks by 50% and more. In two other small studies, low dose ASA (160 mg/daily and 250 mg/daily) did not affect migraine frequency (3, 4). With 3 expections all early trials investigating the migraine prophylactic effect of ASA had small numbers and were were underpowered (see References in Benseñor et al.; 1)
Two larger multicentre trials, however, indicated efficacy of ASA in the prophylaxis of migraine. In 1988 the ‘Bitish Doctors Trial’ showed that a daily dose of 500 mg ASA reduced the frequency of migraine by an average of 30% (5). In the second trial, 325 mg ASA (every other day) was given to 22 071 male American physicians between the age of 40 and 84 years for a period of 60 months, 661 of whom were migraineurs. In this trial, attack frequency was reduced by 20% with ASA (6). These trials indicated the prophylactic (possibly dose-dependent) effect of ASA on migraine frequency.
Only a few trials have compared ASA's prophylactic benefits with other drugs. In a small open trial Baldrati et al. (7) compared the efficacy of ASA (13.5 mg/kg) with propanolol (1.8 mg/kg). In this trial both drugs were equally effective and reduced frequency, duration and intensity of the attacks to the same extent. Other studies were not able to reproduce these results. In a double-blind cross-over trial ASA (500 mg daily) was statistically less effective when compared to 200 mg propanolol daily (8).
We performed a study which was published recently in Cephalalgia (9). This was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18–65 years, suffering between 2 and 6 migraine attacks per month were recruited. Main objective was to show equivalence with respect to efficacy defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for four weeks, followed by 16 weeks drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period from 3 to 2 in the ASA group and from 3 to 1 in the metoprolol group. 45.2% of all metoprolol patients were responders compared to 29.6% with ASA. The responder rate for ASA is in the range of the placebo response in other randomised trials. The findings from this trial showed that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects.
Summarizing the results from the larger trials there seems to be a moderate prophylactic effect of ASA for the prophylaxis of migraine. Due to different definitions of migraine and parameters for treatment success it is almost impossible to perform a proper meta-analysis. Therefore we have to wait for another large scale placebo-controlled trial which preferentially should compare a low and a high dose of ASA for migraine prophylaxis. Already now, ASA can be recommended for patients intolerant to other prophylactics such as beta-blockers, 5-HT antagonists or antiepileptic drugs. ASA is indicated in patients with migraine and multiple vascular risk factors or patients at high risk for a migrainous stroke.