Cardiac Uses of Phosphodiesterase-5 Inhibitors

Bryan G. Schwartz, MD; Laurence A. Levine, MD; Gary Comstock, MD; Vera J. Stecher, PhD; Robert A. Kloner, MD, PhD

Disclosures

J Am Coll Cardiol. 2012;59(1):9-15. 

In This Article

Conclusions

PDE5 is expressed throughout the human body, including the pulmonary and systemic vasculature and hypertrophied myocardium. The effects of PDE5Is on pulmonary circulation and the hypertrophied right ventricle have made these agents first-line therapy for many patients with PAH. The PDE5Is also benefit hemodynamic and clinical parameters in patients with CHF, especially those with secondary PAH and right ventricular failure. The clinical utility of PDE5Is in CHF patients requires large-scale clinical testing. The PDE5Is are ideally suited for and have demonstrated benefit in preventing and treating HAPE and HAPH. Cardioprotection has been reported in numerous animal models where PDE5Is reduced infarct size. In some but not all randomized trials, PDE5Is improved clinical parameters in patients with Raynaud's phenomenon. The PDE5Is might be beneficial in combination with nitrates in patients with treatment-resistant hypertension if proven to be safe. Mechanisms of benefit of PDE5Is include pulmonary and systemic vasodilation, increased myocardial contractility, improved endothelial function, and reduced apoptosis, fibrosis, and hypertrophy through mechanisms involving NO, cGMP, protein kinase G, Bcl-2, and Rho kinase inhibition. Further investigation is warranted to verify benefit in the conditions described and might discover a benefit of PDE5Is in other cardiovascular diseases.

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