Adcirca, Revatio May Improve Survival in PH Due to Lung Disease
Greatest benefit found in patients with properly working heart right ventricle
Treatment with Adcirca (tadalafil) or Revatio (sildenafil) may help patients who develop pulmonary hypertension secondary to an interstitial lung disease to live longer, according to a new study from the U.K.
“Patients treated with [these therapies] survived longer than untreated patients,” the researchers wrote, noting a median survival of more than two years versus less than one year.
The greatest benefit of either therapy was found for patients whose right ventricle — one of the heart’s lower chambers — worked as it should. Researchers observed that these patients survived slightly more than 1.5 years longer than those whose right ventricle did not work as well.
“This work reinforces the prognostic importance of right ventricular dysfunction in pulmonary hypertension associated with interstitial lung disease,” Timothy Dawes, PhD, the study’s first author, said in a video outlining the study’s key findings.
These findings “should be validated by a randomized controlled trial of treatment in this patient group,” said Dawes, a lecturer in the faculty of medicine at the National Heart and Lung Institute at Imperial College London.
The study, “Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study,” was published in the journal Respirology.
Interstitial lung disease, known as ILD, occurs when the lungs become scarred, making it difficult to breathe.
Often, the scarring places a strain on the blood vessels — called pulmonary arteries — that feed the lungs with blood and causes pulmonary hypertension. When this happens, the pressure in these blood vessels becomes too high and makes the heart have to pump blood harder than usual, causing it to become larger and weaker over time.
Treatment with Revatio, Adcirca
Adcirca and Revatio are oral vasodilators, which are medications that open (dilate) the blood vessels to ease the symptoms of pulmonary hypertension. Revatio is sold by Pfizer, while Adcirca is sold by United Therapeutics in the U.S. and Eli Lilly in Europe.
These two medications are known as phosphodiesterase 5 (PDE5) inhibitors because they work by blocking PDE5, an enzyme that breaks down a substance called cyclic GMP. This substance helps relax the muscles around the blood vessels.
Blocking PDE5 means that cyclic GMP is not cleared as quickly. This allows the blood vessels to dilate, increases blood flow to the lungs, and lowers blood pressure.
However, the true benefits of such oral medications remain unclear, and drawing on electronic health records of patients may not be of help to researchers when the data are missing, incomplete, or incorrect.
Now, a team of investigators sought to better understand whether treatment with a PDE5 inhibitor may increase survival among people with pulmonary hypertension resulting from a lung disease.
The researchers started with electronic health records of patients who received a diagnosis from Jan. 1, 2000 to Dec. 6, 2021. But to get around the limitations of these records, the team used a method of analysis called Bayesian modeling.
Bayesian modeling analyses allowed the team to overcome the drawbacks of electronic health records and find out how likely is something to happen when one other event occurs.
There were 128 patients in the study. Among them, 74 (58%) had idiopathic pulmonary fibrosis and 17 (13%) had hypersensitivity pneumonitis — an allergic reaction that results from breathing in specific substances (allergens).
For 12 patients (9%), the diagnosis was non-specific interstitial pneumonia, while eight (6%) had undifferentiated interstitial lung disease, and 17 (13%) had another lung disease.
Most (89%) had severe pulmonary hypertension, and two-thirds (66%) had an abnormally working right ventricle.
Treatment for PH due to lung disease
Of all patients, 50 (39.1%) received treatment with a PDE5 inhibitor for a median 363 days, or roughly one year.
All but one of these patient received the PDE5 inhibitor as first-line treatment. Specifically, 47 were given Revatio and two received Adcirca. One patient received a PDE5 inhibitor after initial treatment with an endothelin receptor antagonist, a medication that also helps the muscles to relax.
The patients were followed up for a median 1.17 years, until death (83%), lung transplant (7%), or a final study date of March 1, 2022 (10%), at which time data were censored.
Most patients (58%) remained alive one year after their diagnosis, but this proportion dropped to 22.1% after three years, and 7.7% after five years.
Patients who received treatment with a PDE5 inhibitor survived a median 1.24 years longer than those who did not receive such therapy (2.18 vs. 0.94 years). This translated into a significantly greater chance of living longer as per Bayesian modeling. The difference to those who did not receive any vasodilator at all was about the same (2.18 vs. 0.92 years).
But for patients who had a normally working right ventricle at diagnosis, the benefits of treatment with a PDE5 inhibitor were even larger. They survived a median 4.09 years on treatment with a PDE5 inhibitor versus 1.3 years if they did not receive this treatment.
Notably, median survival was extended by 1.57 years if the right ventricle was working well versus if it did not (2.55 vs. 0.98 years).
While the findings show that treatment with a PDE5 inhibitor may help extend the survival of patients with pulmonary hypertension resulting from a lung disease, “randomized controlled trial confirmation is crucial before recommending widespread implementation,” the researchers concluded.