Comparison of nebivolol versus diltiazem in improving coronary artery spasm and quality of life in patients with hypertension and vasospastic angina: A prospective, randomized, double-blind pilot study

PLoS One. 2020 Sep 11;15(9):e0239039. doi: 10.1371/journal.pone.0239039. eCollection 2020.


Background: Beta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up.

Methods: Fifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline.

Results: Significant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes.

Conclusions: Both nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Angina Pectoris / complications
  • Angina Pectoris / drug therapy*
  • Angina Pectoris / physiopathology
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / therapeutic use
  • Coronary Angiography
  • Coronary Vasospasm / drug therapy*
  • Coronary Vasospasm / etiology
  • Coronary Vasospasm / physiopathology
  • Cytokines / blood
  • Diltiazem / administration & dosage
  • Diltiazem / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Nebivolol / administration & dosage
  • Nebivolol / therapeutic use*
  • Nitric Oxide / metabolism
  • Pilot Projects
  • Prospective Studies
  • Quality of Life
  • Vasodilation / drug effects


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Cytokines
  • Inflammation Mediators
  • Nebivolol
  • Nitric Oxide
  • Diltiazem

Grant support

SJH received funding from Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT [NRF-2018M3A9A8017949]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.