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  • Review Article
  • Published:

A pathophysiological compass to personalize antianginal drug treatment

Nature Reviews Cardiology volume 18, pages 838–852 (2021)Cite this article

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Abstract

Myocardial ischaemia results from coronary macrovascular or microvascular dysfunction compromising the supply of oxygen and nutrients to the myocardium. The underlying pathophysiological processes are manifold and encompass atherosclerosis of epicardial coronary arteries, vasospasm of large or small vessels and microvascular dysfunction — the clinical relevance of which is increasingly being appreciated. Myocardial ischaemia can have a broad spectrum of clinical manifestations, together denoted as chronic coronary syndromes. The most common antianginal medications relieve symptoms by eliciting coronary vasodilatation and modulating the determinants of myocardial oxygen consumption, that is, heart rate, myocardial wall stress and ventricular contractility. In addition, cardiac substrate metabolism can be altered to alleviate ischaemia by modulating the efficiency of myocardial oxygen use. Although a universal agreement exists on the prognostic importance of lifestyle interventions and event prevention with aspirin and statin therapy, the optimal antianginal treatment for patients with chronic coronary syndromes is less well defined. The 2019 guidelines of the ESC recommend a personalized approach, in which antianginal medications are tailored towards an individual patient’s comorbidities and haemodynamic profile. Although no antianginal medication improves survival, their efficacy for reducing symptoms profoundly depends on the underlying mechanism of the angina. In this Review, we provide clinicians with a rationale for when to use which compound or combination of drugs on the basis of the pathophysiology of the angina and the mode of action of antianginal medications.

Key points

  • Antianginal therapies improve coronary vascular oxygen supply to the ischaemic myocardium; reduce heart rate, myocardial work and oxygen consumption; or optimize the energetic efficiency of cardiomyocytes.

  • So far, neither drugs nor interventions that reduce ischaemia prolong survival in patients with chronic coronary syndromes.

  • Although current guidelines recommend β-blockers and calcium-channel blockers as first-line therapy, no evidence exists that these agents are superior to second-line therapies.

  • We provide a compass for the use of antianginal compounds in patients with chronic coronary syndromes that is tailored towards their haemodynamic status, left ventricular function and comorbidities.

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Fig. 1: The haemodynamics of coronary blood flow.
Fig. 2: Cardiac mechano-energetic coupling in the normal and ischaemic heart.
Fig. 3: Modes of action of antianginal drugs, influencing oxygen consumption or supply.
Fig. 4: Mechanisms of nitrate-induced vasodilatation.
Fig. 5: Modulating cardiac metabolism to treat angina.
Fig. 6: Antianginal compass.

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Acknowledgements

G.H. is supported by the Deutsche Forschungsgemeinschaft (DFG; SFB 1116 B8). T.M. is a principal investigator at the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. C.M. is supported by the DFG (Ma 2528/7-1; SFB 894; TRR-219) and the Federal Ministry of Education and Research (BMBF; 01EO1504).

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  1. Comprehensive Heart Failure Center (CHFC), University Clinic Würzburg, Würzburg, Germany

    Edoardo Bertero & Christoph Maack

  2. Institute for Pathophysiology, West German Heart and Vascular Center, University of Duisburg-Essen, Essen, Germany

    Gerd Heusch

  3. Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Thomas Münzel

  4. German Center for Cardiovascular Research (DZHK), Partner site Rhine-Main, Mainz, Germany

    Thomas Münzel

  5. Department of Internal Medicine 1, University Clinic Würzburg, Würzburg, Germany

    Christoph Maack

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C.M. has received honoraria as a lecturer from AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis and Servier and has served as an adviser to Amgen, Boehringer Ingelheim, Novo Nordisk and Servier. The other authors declare no competing interests.

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Bertero, E., Heusch, G., Münzel, T. et al. A pathophysiological compass to personalize antianginal drug treatment. Nat Rev Cardiol 18, 838–852 (2021). https://doi.org/10.1038/s41569-021-00573-w

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