Comorbidities Require Special Treatment Consideration for PAH

Patients with pulmonary arterial hypertension (PAH) tend to be older, which means they may have unique management considerations depending on their comorbidities, according to researchers.

Pulmonary arterial hypertension causes the small blood vessels in lungs become narrow, making the heart to work harder to pump blood into the lungs.

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In addition to being diagnosed more frequently in older patients, PAH is also more frequently diagnosed in patients with cardio-pulmonary comorbidities, which poses challenges to the optimal treatment of PAH, explained the researchers, publishing their insights in the American Journal of Respiratory and Critical Care Medicine.

“In the US, PAH specific therapies are frequently prescribed by non-expert care centers,” wrote the researchers. “In the RePHerral study 33% of patients were found to have misdiagnosis of PAH prior to the referral to an expert care center. Another 30% were started on PAH specific therapy prior to the referral to an expert care center with 57% receiving therapies contrary to the published guidelines. Multiple studies have demonstrated harmful effects of the PAH specific therapies when used in ill-defined patient population. Considering a higher prevalence of comorbid conditions in the US, we recommend that suspected PAH patients should be referred to the expert care centers for further evaluation and accurate assessment.”

Once diagnosed, efficacy of treatment in patients with PAH and comorbidities is not well understood due to underrepresentation in clinical trials. However, it is known that patients with comorbidities are more likely to discontinue treatment, due to tolerability issues, and less likely to achieve low-risk status.

As a result, management strategies must take into account managing the comorbidities. In general, explained the researchers, clinicians should weigh the severity of PAH versus the burden of comorbid conditions, such as chronic obstructive pulmonary disease (COPD), sleep apnea, obesity, diabetes, hypertension, atrial fibrillation, and coronary artery disease.

PAH treatment typically involves combination treatment, including with phosphodiesterase-5 inhibitors (PDE5is) and endothelin receptor antagonists (ERAs). While patients with certain comorbidities, including COPD and sleep apnea, may be able to receive the standard treatment approach, patients with cardiac and pulmonary comorbidities should undergo special considerations for treatment.

Drawing on their personal experience, as well as data from the AMBITION trial, which compared patients with and without cardiovascular comorbidities,² the researchers suggest that patients with group 1 PAH but with other comorbidities are treated with monotherapy. Treatment, wrote the researchers, should be coupled with close monitoring for tolerability concerns.

Sotatercept, recently approved in the United States and in Europe,^3,4 is recommended for early use in these patients with tolerability issues, as common side effects seen with ERAs, such as fluid retention, is less common with the activin signaling inhibitor.

However, for patients with a pulmonary vascular resistance under 5 wood units, when monitored closely, PDE5i monotherapy may be considered.

“It is important to distinguish the pulmonary comorbidity phenotype from group 3 [pulmomary hypertension] and to identify the patients with very low diffusing capacity who may not tolerate aggressive systemic pulmonary vasodilator therapy,” noted the researchers.“We suggest individualized approach in these patients. Risk stratification, while important, may not reflect severity of their comorbid condition.”

References

1. Sahay S, Chakinala MM, Kim N, et al. Contemporary treatment of pulmonary arterial hypertension: A U.S. perspective. Am J Respir Crit Care Med. 2024;210(5):581-592.doi:10.1164/rccm.202405-0914SO.
2. McLaughlin VV, Vachiery J-L, Oudiz RJ, et al. Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial. J Heart Lung Transplant. 2019;38(12):1286-1295. doi:10.1016/j.healun.2019.09.010
3. Bonavitacola J. FDA approves sotatercept, first-in-class treatment for adults with PAH. AJMC^®. March 26, 2024. Accessed September 3, 2024. https://www.ajmc.com/view/fda-approves-sotatercept-first-in-class-treatment-for-adults-with-pah
4. Merck. Merck receives European Commission approval for Winrevair (sotatercept) in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of PAH in adult patients with functional class II-III. August 26, 2024. Accessed August 30, 2024. https://www.merck.com/news/merck-receives-european-commission-approval-for-winrevair-sotatercept-in-combination-with-other-pulmonary-arterial-hypertension-pah-therapies-for-the-treatment-of-pah-in-adult-patients-w/