In IPAH, Even Patients With Comorbidities Can Benefit From PAH Medication

The ESC/ERS 4-strata model predicted the likelihood of improvement in patients with IPAH, regardless of whether or not they had comorbidities.

Patients with idiopathic pulmonary arterial hypertension (IPAH) and comorbidities experience clinical benefits and improved mortality risk with use of PAH medication, although the effect is less compared with patients without comorbidities, according to study findings published in the Journal of Heart and Lung Transplantation.

Investigators compared outcomes of PAH therapies in IPAH patients with and without comorbidities. Comorbidities included hypertension, coronary heart disease, diabetes mellitus, and obesity (body mass index >30 kg/m2). Outcomes measured included changes in World Health Organization (WHO) functional class (FC), 6-minute walking distance (6MWD), levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) or BNP, and risk after initiation of PAH therapies, as well as the survival.

The study involved 1120 treatment-naïve adults with newly diagnosed IPAH between January 1, 2009, and December 31, 2021, who were included in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) database. Of those patients, 208 (19%) had no comorbidities,

641 (57%) had 1 or 2 comorbidities (328 patients with 1 comorbidity and 313 patients with 2 comorbidities), and 271 (24%) had 3 or 4 comorbidities (214 patients with 3 comorbidities and 57 patients with 4 comorbidities). Overall, participants had a median age of 72 years and 61.6% were female.

Risk was assessed using the European Society of Cardiology (ESC)/European Respiratory Society (ERS) 4-strata model. Data up to March 1, 2022, were analyzed, and the first follow-up was defined as the first visit within 3 to 12 months after treatment initiation.

Reaching a low or intermediate-low risk profile might be a reasonable treatment goal in patients with IPAH and comorbidities.

The first follow-up was 4.1 months (range, 3.3-5.6) after baseline. FC improved by at least 1 WHO functional class in 51% of participants without comorbidities, in 33% of patients with 1 or 2 comorbidities, and in 28% of patients with 3 or 4 comorbidities. The 6MWD improved by 43 meters (range, -3 to 100), 30 meters (range, -10 to 71), and 30 meters (range, 0 to 68) in the 3 groups, respectively. The BNP/NT-proBNP level changes were -45% (range, -77 to 0), -26% (range, -59 to 18), and -20% (range, -56 to 38), respectively, in the 3 groups.

Improvements for all variables were significantly greater in patients with no comorbidities vs in the 2 groups of patients with comorbidities. They were not significantly different in patients with 1 to 2 vs 3 to 4 comorbidities.

According to the ESC/ERS 4-strata model, risk improved in 52% of participants who did not have comorbidities and in 33% and 34% of the patients with 1 to 2 and 3 to 4 comorbidities, respectively. For the patients with comorbidities, improvements in risk were primarily accounted for by improvements from the intermediate-high risk category to the intermediate-low risk category.

Older age, male sex, high baseline risk, number of comorbidities, and a low lung diffusion capacity for carbon monoxide were associated with an increased mortality risk in the Cox proportional hazard analysis. When all 4 comorbidities (hypertension, diabetes mellitus, coronary heart disease, and obesity) were included in the Cox proportional hazard model instead of the number of comorbidities, the only comorbidities associated with increased mortality risk were coronary heart disease (hazard ratio [HR] 1.35; 95% CI, 1.05-1.74, P = .0186) and diabetes (HR 1.28; 95% CI 1.01-1.63, P = .0444).

Statistically significant unadjusted survival differences among the 3 cohorts were observed (P <.0001). After adjustment for age and sex, the survival differences were no longer statistically significant for patients with 1 to 2 and 3 to 4 comorbidities vs patients without comorbidities.

Study limitations include: missing values for some variables, including those required for risk stratification; a small number of patients lost to follow-up; and the fact that investigators determined the diagnostic classification of IPAH.

“The ESC/ERS 4-strata model predicted outcome in patients with IPAH irrespective of the absence or presence of comorbidities,” stated the researchers. “Reaching a low or intermediate-low risk profile might be a reasonable treatment goal in patients with IPAH and comorbidities.”

Disclosure: COMPERA is funded by unrestricted grants from Acceleron, Bayer, Ferrer, Janssen, and OMT. Some of study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Rosenkranz S, Pausch C, Coghlan JG, et al. Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: a COMPERA analysis. J Heart Lung Transplant. Published online October 13, 2022. doi:10.1016/j.healun.2022.10.003