Relative efficacy of antianginal drugs used as add-on therapy in patients with stable angina: A systematic review and meta-analysis

Eur J Prev Cardiol. 2015 Jul;22(7):837-48. doi: 10.1177/2047487314533217. Epub 2014 Apr 28.


Aims: First-line medical management of stable angina generally involves a beta-blocker (BB) or calcium channel blocker (CCB), with other classes of medication being added if symptom control is inadequate. Evidence supporting the appropriate choice of a second-line agent is currently unclear. The objective of this systematic review was to quantify the clinical benefit of BB, CCBs, long-acting nitrates (LANs), ranolazine, trimetazidine, ivabradine or nicorandil added to first-line monotherapy for stable coronary artery disease.

Methods: Randomised controlled trials comparing the efficacy of antianginal therapies in patients with stable angina refractory to first-line therapy were identified from a literature search. Exercise tolerance test (ETT) data and clinical outcomes were extracted and combined in a series of meta-analyses.

Results: A total of 46 qualifying studies were identified, evaluating 71 treatment comparisons. The combination of ranolazine added to CCB or BB showed positive outcomes across all outcomes assessed. Other combinations of BB, CCB, LAN and trimetazidine showed significant benefits for most but not all outcomes. Ivabradine demonstrated benefits for ETT assessments but these were not matched in clinical domains. No qualifying studies were identified for nicorandil in an add-on role.

Conclusion: Across a range of commonly assessed exercise and clinical outcomes, the effectiveness of BB+CCB used in combination is broadly confirmed. Ranolazine used with BB or CCB showed benefits across all outcomes assessed, while LAN and trimetazidine used with BB or CCB have shown benefits across some outcomes. Ivabradine added to BB shows inconsistent effects from a single study, whilst there is no relevant evidence for nicorandil.

Keywords: Stable angina; antianginal therapy; beta blocker; calcium antagonist; ivabradine long acting nitrate; meta-analysis; nicorandil; ranolazine; trimetazidine.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Angina, Stable / diagnosis
  • Angina, Stable / drug therapy*
  • Angina, Stable / physiopathology
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Drug Therapy, Combination
  • Exercise Test
  • Exercise Tolerance / drug effects
  • Humans
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Vasodilation / drug effects
  • Vasodilator Agents / therapeutic use


  • Cardiovascular Agents
  • Vasodilator Agents