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


J Am Coll Cardiol. 2012;59(1):9-15. 

In This Article

Raynaud's Phenomenon

The effects of PDE5Is on systemic vasodilation and endothelial function might benefit patients with Raynaud's phenomenon. In an open-label pilot study in 40 patients with Raynaud's disease, vardenafil 10 mg twice daily improved digital blood flow in 70% of patients and improved clinical symptoms in 68%.[45] In a crossover study, sildenafil reduced the frequency and duration of Raynaud's attacks and markedly increased capillary blood flow velocity.[46] Moreover, visible healing was noted in all 6 patients with chronic digital ulcerations, all 16 patients correctly identified the double-blinded pills as either sildenafil or placebo, and 89% of patients requested to continue sildenafil as off-label therapy after the conclusion of the study.[46] Furthermore, in 19 patients with systemic sclerosis and digital ulcers refractory to treatment, the number of digital ulcers decreased from 3.1 to 1.1 ulcers/patient during sildenafil therapy for a mean of 5.2 months.[47] Approximately one-half of patients developed new ulcers during sildenafil therapy, suggesting that sildenafil does not prevent new ulcerations.[47] Previously, bosentan, an endothelin-1 receptor antagonist, failed to heal digital ulcers but was effective in preventing them.[47] Thus, different mechanisms might be involved in preventing and healing digital ulcers, and combination therapy might be beneficial. Two other crossover studies did not demonstrate a benefit with tadalafil therapy; however, it was noted that placebo response was a factor.[48,49] In a double-blind, randomized study accepted for publication, sildenafil significantly reduced the frequency of Raynaud's attacks compared with placebo.[50] In conclusion, PDE5Is are promising for the treatment of Raynaud's patients, and additional placebo-controlled trials are needed to clarify dosing and subsets of patients most likely to benefit from PDE5I therapy.