PDE5 Inhibitors Can Help Some Pulmonary Hypertension Patients With Left Heart Disease

Compounds that increase the amount of blood flowing through heart vessels can benefit people with pulmonary hypertension (PH) and chronic left heart disease who have decreased blood-pumping ability, according to an analysis of several studies.

The compounds are phosphodiesterase-5 (PDE5) inhibitors such as Revatio (sildenafil). They prevent an enzyme called PED5 from hindering the cGMP molecule’s ability to relax blood-vessel muscles. Relaxing the muscles allows more blood to flow through the vessels.

Revatio and other PDE5 inhibitors can help people with PH or chronic left heart disease who have a less than adequate score on a measure of blood-pumping ability known as ventricular ejection fraction. The score measures how well the heart’s ventricle pumps blood with each heart beat.

Those with an adequate ejection fraction score did not seem to benefit from PDE5 treatment, the Italian researchers said. But the number of patients with adequate scores was limited, prompting the team to suggest that the group needs to be studied further.

Pulmonary hypertension is a disease that involves higher than normal blood pressure in the pulmonary artery, pulmonary vein or pulmonary capillaries. The higher pressure can stem from constricted blood vessels. PH leads to shortness of breath, dizziness, fainting, leg swelling and other symptoms.

The researchers’ review of the previous studies, titled, “Phosphodiesterase-5 Inhibitors Improve Clinical Outcomes, Exercise Capacity and Pulmonary Hemodynamics in Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction: A Meta-Analysis,” was published in the Journal of Clinical Medicine Research.

PDE5 inhibitors have been studied in several clinical trials in patients with type 2 pulmonary hypertension caused by a diseased left side of the heart. But the results of the studies have varied. That prompted researchers at an Italian hospital to do a meta-analysis, or pooling of data from several studies to obtain a larger patient sample.

Most of the 14 studies that researchers at the Presidio Sanitario Intermedio Elena d’Aosta, ASL Napoli included in their analysis were randomized clinical trials. One was a subgroup study. In total, 928 patients with chronic heart failure were included in the analysis.

Patients with left heart disease can have either preserved or reduced ejection fraction.

Five hundred fifty-five of the patients in the analysis had diminished ejection fraction. Of the 555, those treated with a PDE5 inhibitor were at 72 percent lower risk of having a negative disease outcome score that combined hospitalizations and death, compared with patients who received a placebo. The treatment also led to higher oxygen-consumption rates and exercise-capacity scores.

In addition, the inhibitors increased the amount of blood patients were able to pump out of their left ventricle, improving their ejection fraction scores.

Researchers also looked at patients’ lung blood pressure. They found improvements in mean pulmonary arterial pressure readings, although the changes were not significant. But they also discovered significant reductions in pulmonary arterial systolic pressure readings.

In contrast, PDE5 inhibitors failed to benefit the 373 patients with preserved ejection fraction, researchers said. They called for further studies in this patient population.