PDE5 Inhibitors Improve Blood Flow, Exercise Capacity in PH: Analysis

But such vasodilators don't lower risk of death, data show

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with phosphodiesterase-5 (PDE5) inhibitors can improve blood flow parameters and exercise capacity in people with pulmonary hypertension (PH), according to a new analysis of clinical trial data.

“The study found that the reduction in mean PAP [peripheral arterial pressure] was significantly greater in patients receiving PDE5 inhibitors,” the researchers wrote, noting that a potential “reduction in pressure could cause … enhanced heart rate, and cardiac output.”

However, the analyses showed that PDE5 inhibitors — a blood pressure medication — do not significantly lower the risk of death or hospitalization in PH.

Titled “Effect of Phosphodiesterase-5 (PDE-5) Inhibitors on Clinical Outcomes in Patients With Pulmonary Hypertension: A Meta-Analysis of Randomized Control Trials,” the study was published in the journal Cureus.

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Improvements found in blood dynamics, exercise capacity

PDE5 inhibitors are a class of vasodilators, or medicines that work to lower blood pressure by relaxing and widening blood vessels. Several PDE5 inhibitors are approved for the management of PH, such as Adcirca (tadalafil) and Revatio (sildenafil).

Researchers noted that there have been “major contributions … in the last decade” in the treatment of PH.

“The aim of this meta-analysis is to determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults,” they wrote. Meta-analysis is a strategy in which scientists pool data from multiple different studies and analyze it collectively.

Here, the team specifically examined the efficacy of PDE5 inhibitors in clinical trials for any type of PH.

The meta-analysis included data from 17 clinical trials that tested a PDE5 inhibitor against a placebo or another treatment. Specifically, 13 of the studies evaluated Revatio, three tested Adcirca, and one tested vardenafil (sold under the brand names Levitra and Staxyn as treatments for erectile dysfunction).

Results from the meta-analysis showed that PDE5 inhibitor treatment led to a significant increase in cardiac index — a measure of the cardiac ouput, the total amount of blood that the heart can pump out through the body, based on the patient’s size. PDE5 inhibitor treatment also significantly decreased blood pressure in the lung’s blood vessels compared with the control group.

The distance patients could walk in six minutes (6MWD), a common measure of exercise capacity, also improved significantly with PDE5 inhibitor treatment, by more than 26 meters (85 feet) on average relative to controls.

“Beneficial impacts of PDE5 inhibitors were visible across all three drugs” included in the analysis, the researchers noted, though they stressed that none of the 17 studies had head-to-head treatment comparisons.

Meta-analysis results showed a trend toward less mortality and fewer hospitalizations for patients on PDE5 inhibitor treatment compared with those on a placebo; however, the difference did not reach statistical significance (meaning that, mathematically, there’s a non-negligible likelihood the difference is due to random chance).

“The current meta-analysis showed clear clinical and statistical benefits for the utilization of PDE5 inhibitors in patients with PH compared to placebo in relation to 6MWD, mean PAP [pulmonary arterial pressure], and cardiac index. However, no significant difference was reported in terms of mortality and hospitalization between the two groups,” the researchers concluded.

The team noted that this analysis is limited by the small size and short duration of the published clinical studies, highlighting a need for larger, longer trials to further explore the effectiveness of PDE5 inhibitors for PH treatment.

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