Outcome of Patients with Severe PH due to Lung Disease with and without Targeted Therapy

Abstract

SUMMARYIntroduction: Pulmonary hypertension (PH) can occur in patients with lung disease and worsen prognosis. Endothelin receptor antagonists, phosphodiesterase 5-inhibitors, and prostacyclin analogs, referred to as targeted therapy, have not been shown in a limited number of controlled clinical studies to improve exercise capacity in these patients. Possibly targeted therapy could be of benefit in patients with severe PH due to lung disease, but this subgroup is not well studied. Aims: To analyze influence of PH severity and use of targeted therapy on exercise capacity and survival in patients with PH due to lung disease. Methods: Consecutive patients with PH (mean pulmonary artery pressure ≥25 mmHg at rest) due to lung disease diagnosed by right heart catheterization between 1/2005 and 9/2011 were retrospectively included. Severe PH was defined as mean pulmonary artery pressure ≥35 mmHg. Patients were followed until 4/2012 for exercise capacity, survival, and targeted therapy use. Results: Patients with severe PH (n = 40) received significantly more often targeted therapy compared to the 32 patients with less severe PH (65% vs. 25%, P = 0.001). Survival was not significantly different between these groups (P = 0.310). Patients on targeted therapy were older, more often female, and had worse hemodynamic impairment, but significantly higher estimated 1-, 3-, and 5-year survival rates compared to untreated patients (97%, 81%, and 75% vs. 83%, 54%, and 19%, respectively; P = 0.002). This effect was mainly driven by the patients with severe PH, in whom the survival advantage was statistically significant on subgroup analysis (HR 0.182, P = 0.002). Exercise capacity was not significantly altered in any patient group. Conclusion: Patients with severe PH due to lung disease may have a survival benefit from targeted therapy compared to untreated patients with less severe PH. Prospective clinical trials utilizing targeted therapy and long-term endpoints are justified in this patient group.

Sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A Phase IIb, randomised, double-blind, placebo-controlled study – Rationale and study design

“…Studies of ET receptor antagonists have specifically targeted fibrosis rather than the complicating PH. Although a few studies have shown that targeted therapy with PDE-5 inhibitors or prostacyclin analogues can improve exercise capacity [46], the use of targeted therapy in patients with PH in the context of significant lung disease is not supported by evidence derived from randomised controlled trials, and there is no agent with regulatory approval for this indication.…”

Long-term Effect of Vasodilator Therapy in Pulmonary Hypertension due to COPD: A Retrospective Analysis

“…However, other studies reached contradictive results. Lange et al recently described a better survival in a retrospective cohort of treated PH-COPD, but no effect of therapy on the exercise capacity [19]. Blanco et al investigated the effect of sildenafil given for 3 months in addition to training to COPD patients with mild PH at echocardiography [20].…”

Group 3 pulmonary hypertension: Challenges and opportunities

“…Pulmonary hypertension is commonly associated with chronic lung disease, but severe PH is rare, defined as mPAP of ≥35 mmHg. Lange et al did show a survival benefit with vasodilators in patients with severe PH in lung disease, but not in the mild/moderate groups 46 . It has been shown that although pulmonary vasodilators do reduce NTproBNP in severe Group 3 PH, there was no significant increase in 6-minute walk distance.…”