title: Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.
abstract: OBJECTIVE
  Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA.
  
  
  RESULTS
  A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered.
  
  
  CONCLUSIONS
  Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Nihei
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Odaka
authors.affiliation: Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Tsunoda
authors.affiliation: Sakakibara Heart Institute, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Seki
authors.affiliation: Sakakibara Heart Institute, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sumiyoshi
authors.affiliation: Yamagata Prefectural Central Hospital, Yamagata, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Matsui
authors.affiliation: Yamagata Prefectural Central Hospital, Yamagata, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Goto
authors.affiliation: Niigata Prefectural Shibata Hospital, Shibata, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Ehime Prefectural Niihama Hospital, Niihama, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Sueda
authors.affiliation: Jichi Medical University Saitama Medical Center, Saitama, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Momomura
authors.affiliation: National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan shimo@cardio.med.tohoku.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002908:Chronic Disease; D003329:Coronary Vasospasm / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007547:Isosorbide / Q000627:therapeutic use; D008297:Male; D020108:Nicorandil / Q000627:therapeutic use; D009566:Nitrates / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies
chemical_list: D002121:Calcium Channel Blockers; D009566:Nitrates; D020108:Nicorandil; D005996:Nitroglycerin; D007547:Isosorbide
keywords: Coronary vasospasm; Nicorandil; Nitrate; Prognosis; Vasospastic angina