Mono and combination therapies in pulmonary arterial hypertension patients with comorbidities: A COMPERA analysis

Abstract

Aims: Pulmonary arterial hypertension (PAH) is often diagnosed in elderly patients with comorbidities. Although initial monotherapy is recommended for these patients, the value of combination therapy remains unclear. Here, we compare the efficacy of initial monotherapy and combination therapy in PAH patients with cardiovascular comorbidities.

Methods and results: Data from adult patients with incident pre-capillary PAH and cardiovascular comorbidities from the COMPERA database (European registry for PH) were analysed. A matched-pair analysis of patients treated with monotherapy versus combination therapy based on age, sex, WHO functional class (FC) and 4-strata risk at baseline was performed. The matching strategy identified 216 pairs of PAH patients with cardiovascular comorbidities, who differed considerably from the enrolled patient population (n = 1871), especially in terms of mean age (mono: matched pairs 62.9 ± 13.5 years vs. 70.6 ± 11.4 years, combination: matched pairs 62.0 ± 13.6 years vs. 60.5 ± 14.9 years). In the matched-pair analysis, the initial combination therapy group showed more pronounced improvements in WHO-FC, N-terminal pro-B-type natriuretic peptide (BNP/NT-proBNP) and risk status than patients treated with initial monotherapy, with no significant differences in 6-min walk distance (6MWD), PAH-related hospitalisations, survival and drug discontinuation.

Conclusions: This analysis suggests that PAH patients with comorbidities may benefit more pronounced from combination therapy regarding WHO-FC, BNP/NT-pro-BNP and risk status without a significant difference in survival. Good tolerability is indicated. However, given the relatively younger patient matched subgroup, these findings may not necessarily apply to older patients with a wider range of comorbidities.

Keywords: COMPERA database; PAH and comorbidities; initial monotherapy and combination therapy; matched‐pair analysis.

Figure 1

Strobe diagram of patient cohort selection process. FC, World Health Organization (WHO) Functional Class (FC); mmHg, millimetres of mercury; mPAP, mean pulmonary arterial pressure; PAH, pulmonary arterial hypertension; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance.

Figure 2

Risk stratification at first follow‐up according to initial treatment strategy among patients with at least one cardiovascular comorbidity (after matching on age, sex, FC and risk status).

Figure 3

(A) Kaplan–Meier curves with 95% confidence intervals for transplant‐free survival time of all matched patients with comorbidities, monotherapy versus combination therapy. Survival estimates at 1 year are 91.3% (95% CI [87.5; 95.2]%) for monotherapy group and 90.7% (95% CI [86.8; 94.8]%) for combination therapy group. Survival estimates at 3 years are 70.2% (95% CI [63.6; 77.4]%) for the monotherapy group and 71.1% (95% CI [64.4; 78.5]%) for the combination therapy group. The survival estimates at 5 years are 49.0% (95% CI [41.1; 58.3]%) for monotherapy group and 56.7% (95% CI [48.5; 66.3]%) for the combination therapy group. (B) Kaplan–Meier curves with 95% confidence intervals for time to PH related hospitalisation of all matched patients with comorbidities, monotherapy versus combination therapy. Survival estimates at 1 year are 72.6% (95% CI [66.6; 79.1]%) for monotherapy group and 74.5% (95% CI [68.6; 80.9]%) for combination therapy group. Survival estimates at 3 years are 52.3% (95% CI [45.0; 60.8]%) for monotherapy group and 61.4% (95% CI [53.9; 70.1]%) for combination therapy group. Survival estimates at 5 years are 43.3% (95% CI [35.5; 52.9]%) for monotherapy group and 49.8% (95% CI [40.5; 61.3]%) for combination therapy group. (C) Kaplan–Meier curves with 95% confidence intervals for time to first discontinuation of therapy (monotherapy to no therapy and combination to monotherapy) of all matched patients with comorbidities, monotherapy versus combination therapy.