Impact of different nitrate therapies on long-term clinical outcomes of patients with vasospastic angina: A propensity score-matched analysis

Background Despite the short-term vasodilatory effects of nitrates, the prognostic effects of long-term nitrate therapy in patients with vasospastic angina (VSA) remains unclear. We investigated the prognostic impact of chronic nitrate therapy in VSA patients. Methods Between January 2003 and December 2014, a total of 1154 VSA patients proven by ergonovine provocation tests were classified into nitrate (n = 676) and non-nitrate (n = 478) groups according to prescriptions for oral nitrates, including isosorbide mononitrate (ISMN) and nicorandil. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, myocardial infarction, any revascularization, or rehospitalization due to recurrent angina. Results The nitrate group was found to have a higher risk of MACE (22.9% vs. 17.6%, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.01–1.73, p = 0.043) than the non-nitrate group. After propensity score matching, the nitrate group had greater risks of MACE (HR 1.32, 95%CI 1.01–1.73, p = 0.049). Patients who received the immediate-release formula of ISMN (HR 1.80, 95%CI 1.35–2.39, p < 0.001) or were administered any forms of ISMN other than at bedtime (HR 1.90, 95%CI 1.41–2.57, p < 0.001) had a significantly higher risk of MACE compared with the non-nitrate group. Nicorandil was shown to have a neutral effect on VSA patients (HR 1.11, 95%CI 0.73–1.69, p = 0.62). Conclusions The long-term use of nitrate therapy was associated with increased risk of adverse cardiac events in VSA patients. The use of immediate-release ISMN or the administration of ISMN other than at bedtime was related with poor outcomes of VSA patients.