Nitrate-induced headache in patients with stable angina pectoris:Beneficial effect of starting on a low dosage

Background: Nitrates, although important for the management of angina pectoris, cause significant headache in many patients.Methods: In a randomized, double-blind, crossover study, 89 patients with stable angina pectoris were studied to compare two different dosage strategies of isosorbide-5-mononitrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (ed) for two weeks or to 30 mg 5-ISMN od for one week followed by 60 mg 5-ISMN od for one week. Then, there was a two-week placebo washout, after which the alternative treatment was given. The authors assessed the occurrence of angina pectoris and headache by diary cards while taking into account the numbers of isosorbide dinitrate sublingual puffs and paracetamole tablets required. Data were assessed for carryover and time effects.Results: The two dosage regimens were equally efficient for the relief of angina pectoris without development of tolerance. Thirty percent of the patients never experienced headache from the given dosages. In the remainder of them there was a highly significant time effect: the overall numbers of headache attacks in the first period of active treatment versus the second were 2,380 vs 1,400 (P <0.003). Yet significantly fewer patients had headache on low dosage than oil high dosage (45 vs 57, P <0.02).Conclusions: (1) Starting on a low dosage-was associated with a reduced frequency and severity of headache and did not notably influence the beneficial effect on angina pectoris. (2) One in 3 patients never experienced headache from the given dosages. (3) The overall number of headache attacks in the first period of active treatment was significantly higher than in the second period irrespective of the dosages given.