Perspective:

The following are 10 points to remember about this state-of-the-art paper on cardiac uses of phosphodiesterase-5 inhibitors (PDE5Is):

1. PDE5Is result in enhanced vasodilation by inhibiting the breakdown of cyclic guanosine monophosphate (cGMP), and protect myocytes directly through complex mechanisms (cardiac remodeling, apoptosis, fibrosis, and hypertrophy).

2. Small trials in congestive heart failure (CHF) patients have shown the greatest benefit (improved clinical and hemodynamic parameters) of PDE5Is in patients with secondary peripheral arterial hypertension (PAH) and right ventricular failure. The utility of PDE5Is in CHF patients without PAH is less clear.

3. Animal models (using sildenafil or tadalafil) suggest that prophylactic PDE5Is may be beneficial for patients treated with doxorubicin (without interfering with the chemotherapeutic benefit of doxorubicin).

4. Animal models have shown that sildenafil, tadalafil, and vardenafil reduce infarct size when given 30-120 minutes before coronary occlusion, suggesting PDE5Is are cardioprotective.

5. Small clinical studies suggest that PDE5Is might prevent and improve high altitude pulmonary edema and high altitude pulmonary hypertension.

6. The combination of PDE5Is and nitrates might be beneficial for patients with treatment-resistant hypertension, as shown in a small study; however, more safety data are needed for this combination.

7. PDE5I monotherapy results in small or moderate reductions in blood pressure.

8. PDE5Is are promising for the treatment of Raynaud’s patients (including improved symptoms, decreased frequency and duration of recurrent attacks, and better healing of digital ulcerations).

9. In an animal model of unilateral hindlimb ischemia mimicking peripheral arterial disease, PDE5I (using either sildenafil or vardenafil) enhanced ischemia-induced angiogenesis, as measured by vascular perfusion, tissue blood flow, and vascular density.

10. It has been hypothesized (but not tested) that PDE5Is may be beneficial in pre-eclampsia and in patients undergoing cardiac surgery.