Drugs targeting pulmonary arterial hypertension often do not have clinical or functional benefits, a meta-analysis shows, for patients with comorbid pulmonary (PH) hypertension/chronic obstructive pulmonary disease (COPD).
A new systematic review of studies probing therapies for patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD-PH) affirms guidelines that call for supplemental long-term oxygen therapy (LTOT) in hypoxemic patients.
The study also found, however, that medications targeting pulmonary arterial hypertension (PAH) are generally ineffective solutions for such patients. The report was published in ERJ Open Research.
The authors explained that the presence of PH in patients with COPD is associated with adverse outcomes, including increased mortality.
“For example, severe PH and resulting right ventricular failure are associated with more severe dyspnea and limited exercise capacity,” they wrote. “Indeed, the presence of PH has a stronger association with mortality in COPD than forced expiratory volume in 1 second or gas exchange variables.”
It is not clear exactly how many patients with COPD also have PH, but the authors said data suggest those with severe COPD are more likely to have PH.
Given the high stakes for this patient group, they set out to see what the existing literature might say with regard to the benefits of particular treatments for COPD-PH. They conducted a search of articles published between 1947 and 2020, selecting studies with at least 10 patients and that tracked treatment response for at least 4 weeks.
After initially identifying more than 4500 studies, the investigators narrowed their list to 46 studies that met all of their inclusion criteria. Half were randomized controlled trials (covering 1159 patients), and the other half were nonrandomized controlled trials (covering 1187 patients).
Eight of the studies looked at LTOT, most of which followed patients for at least a year. These studies showed mixed benefits: 5 of the studies showed modest reductions in mean pulmonary artery pressure and/or pulmonary vascular resistance, and 3 reported no change in cardiac output.
“In summary, in COPD-PH patients with hypoxemia, LTOT may mildly reduce severity of PH, slow PH progression over time, and reduce mortality, but without any other clinical or functional benefit,” the authors said.
They also found several studies that looked at the potential benefits of PAH-targeting medications, including oral phosphodiesterase type 5 inhibitors (PDE-5i), oral endothelin receptors antagonists, and prostanoids.
The data showed such medications, broadly speaking, had inconsistent effects. The PDE-5i sildenafil (Viagra) improved hemodynamics but had “uncertain” clinical or functional benefits.
Only 4 studies examined calcium channel blockers, but they suggested that the therapy was poorly tolerated and led only to mild hemodynamic improvement without any corresponding clinical or survival benefits. Statins, on the other hand, were well tolerated, although they did not yield clinical or functional benefits.
Taken as a whole, they authors said only LTOT appeared to be significantly effective.
“This review supports recent guidelines, which recommend LTOT in hypoxemic COPD-PH patients but do not recommend other treatments for COPD-PH, including PAH-targeted medications,” they concluded.
They added that new ideas are needed with regard to the pathobiology of COPD-PH in order to develop better therapies and that future studies of potential therapies should include more homogenous populations with a standardized diagnosis based on right heart catheterization and a comprehensive assessment of outcomes.
Arif R, Pandey A, Zhao Y, Arsenault-Mehta K, Khoujah D, Mehta S. Treatment of pulmonary hypertension associated with COPD: a systematic review. ERJ Open Res. Published online February 21, 2022. doi:10.1183/23120541.00348-2021