Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: Multicentre registry study of the Japanese coronary spasm association

Jun Takahashi, Taro Nihei, Yusuke Takagi, Satoshi Miyata, Yuji Odaka, Ryusuke Tsunoda, Atsushi Seki, Tetsuya Sumiyoshi, Motoyuki Matsui, Toshikazu Goto, Yasuhiko Tanabe, Shozo Sueda, Shin Ichi Momomura, Satoshi Yasuda, Hisao Ogawa, Hiroaki Shimokawa

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57 Citations (Scopus)


Aims 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. Methods and 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.

Original languageEnglish
Pages (from-to)228-237
Number of pages10
JournalEuropean Heart Journal
Issue number4
Publication statusPublished - 2015 Jan 21


  • Coronary vasospasm
  • Nicorandil
  • Nitrate
  • Prognosis
  • Vasospastic angina

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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