Most inconsistent treatments for patients with PH and COPD, review finds

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Drugs targeting pulmonary arterial hypertension often have no clinical or functional benefits, according to a meta-analysis, for patients with comorbid pulmonary hypertension (PH)/chronic obstructive pulmonary disease (COPD).

A new systematic review of studies investigating therapies for patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD-PH) confirms guidelines that call for long-term supplemental oxygen therapy (LTOT) in hypoxemic patients.

The study also found, however, that drugs targeting pulmonary arterial hypertension (PAH) are generally ineffective solutions for these patients. The report was published in Open research ERJ.

The authors explained that the presence of PH in patients with COPD is associated with adverse effects, 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’s unclear exactly how many patients with COPD also have PH, but the authors said the data suggests that people with severe COPD are more likely to have PH.

Given the high stakes for this group of patients, they set out to see what the existing literature might say regarding the benefits of particular treatments for COPD-PH. They searched for articles published between 1947 and 2020, selecting studies with at least 10 patients and which followed treatment response for at least 4 weeks.

After initially identifying more than 4,500 studies, the researchers narrowed down 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 non-randomised controlled trials (covering 1187 patients).

Eight of the studies looked at OTLD, 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 arterial pressure and/or pulmonary vascular resistance, and 3 reported no change in cardiac output.

“In summary, in COPD-PH patients with hypoxemia, OTL may slightly reduce PH severity, 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 drugs, including oral phosphodiesterase type 5 (PDE-5i) inhibitors, oral endothelin receptor antagonists, and prostanoids.

The data showed that these drugs, in general, had inconsistent effects. Sildenafil PDE-5i (Viagra) improved hemodynamics but had “uncertain” clinical or functional benefits.

Only 4 studies looked at calcium channel blockers, but they suggested that the treatment was poorly tolerated and only resulted in a slight hemodynamic improvement with no corresponding clinical or survival benefit. Statins, on the other hand, were well tolerated, although they did not provide clinical or functional benefits.

Taken together, the authors said only LTOT appeared to be significantly effective.

“This review supports recent guidelines, which recommend OTLD in hypoxemic patients with COPD-PH, but do not recommend other treatments for COPD-PH, including drugs targeting PAH,” they wrote. concluded.

They added that new insights are needed regarding the pathobiology of COPD-PH in order to develop better therapies and that future studies of potential therapies should include more homogeneous populations with standardized diagnosis based on right heart catheterization. and a full evaluation of the results.

Reference

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

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