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Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety

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Abstract

The coexistence of cardiovascular disease and erectile dysfunction is widespread, possibly owing to underlying endothelial dysfunction in both diseases. Millions of patients with cardiovascular disease are prescribed phosphodiesterase-5 (PDE5) inhibitors for the management of erectile dysfunction. Although the role of PDE5 inhibitors in erectile dysfunction therapy is well established, their effects on the cardiovascular system are unclear. Preclinical studies investigating the effect of PDE5 inhibitors on ischemia–reperfusion injury, pressure overload-induced hypertrophy, and chemotoxicity suggested a possible clinical role for each of these medications; however, attempts to translate these findings to the bedside have resulted in mixed outcomes. In this review, we explore the biologic preclinical effects of PDE5 inhibitors in mediating cardioprotection. We then examine clinical trials investigating PDE5 inhibition in patients with heart failure, coronary artery disease, and ventricular arrhythmias and discuss why the studies likely have yet to show positive results and efficacy with PDE5 inhibition despite no safety concerns.

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Acknowledgements

The authors express their gratitude to Jason Miller for his assistance with the figure.

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Authors and Affiliations

  1. Pauley Heart Center, Virginia Commonwealth University Medical Center, McGuire VAMC, 1201 Broad Rock Boulevard, 111J, Richmond, VA, 23249, USA

    Sumon Roy, Fadi N. Salloum & Ion S. Jovin

  2. Huntington Medical Research Institute, Pasadena, CA, USA

    Robert A. Kloner

  3. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Robert A. Kloner

  4. McGuire Veterans Affairs Medical Center, Richmond, VA, USA

    Ion S. Jovin

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  1. Sumon Roy
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  2. Robert A. Kloner
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  3. Fadi N. Salloum
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  4. Ion S. Jovin
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ISJ and SR had the idea for the article. SR wrote the first draft. All authors contributed to literature search, drafting, and critically revising the work. All authors approved the final version.

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Correspondence to Ion S. Jovin.

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Dr. Robert Kloner is a paid consultant for Sanofi. Dr. Fadi Salloum is funded by the National Institutes of Health (R35 HL155651).

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Roy, S., Kloner, R.A., Salloum, F.N. et al. Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety. Cardiovasc Drugs Ther 37, 793–806 (2023). https://doi.org/10.1007/s10557-021-07275-y

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