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

Eur Heart J. 2015 Jan 21;36(4):228-37. doi: 10.1093/eurheartj/ehu313. Epub 2014 Sep 4.


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.

Keywords: Coronary vasospasm; Nicorandil; Nitrate; Prognosis; Vasospastic angina.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina Pectoris / drug therapy*
  • Calcium Channel Blockers / therapeutic use
  • Chronic Disease
  • Coronary Vasospasm / drug therapy*
  • Female
  • Humans
  • Isosorbide / therapeutic use
  • Male
  • Nicorandil / therapeutic use
  • Nitrates / therapeutic use*
  • Nitroglycerin / therapeutic use
  • Prognosis
  • Prospective Studies
  • Registries
  • Retrospective Studies


  • Calcium Channel Blockers
  • Nitrates
  • Nicorandil
  • Nitroglycerin
  • Isosorbide