Chung Hun Kim1, Taek Kyu Park2, Sung Woo Cho3, Min Seok Oh4, Da Hyon Lee2, Choong Sil Seong2, Hye Bin Gwag2, A Young Lim2, Jeong Hoon Yang2, Young Bin Song2, Joo-Yong Hahn2, Jin-Ho Choi2, Sang Hoon Lee2, Hyeon-Cheol Gwon2, Joonghyun Ahn5, K C Carriere6, Seung-Hyuk Choi7. 1. Division of Cardiology, Department of Internal Medicine, Hyemin General Hospital, Seoul, Republic of Korea. 2. Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea. 3. Division of Cardiology, Department of Internal Medicine, Inje University, College of Medicine, Seoul Paik Hospital, Seoul, Republic of Korea. 4. Cardiovascular Center, Department of Internal Medicine, Bundang Jesaeng Hospital, Daejin Medical Center, Gyeonggi-do, Republic of Korea. 5. Department of Biostatistics and Clinical Epidemiology, Samsung Medical Center, Seoul, Republic of Korea. 6. Department of Biostatistics and Clinical Epidemiology, Samsung Medical Center, Seoul, Republic of Korea; Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, Canada. 7. Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea. Electronic address: cardiochoi@skku.edu.
Abstract
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.
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.