Mortality in Pulmonary Arterial Hypertension in the Modern Era: Early Insights From the Pulmonary Hypertension Association Registry

Abstract

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan-Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment-naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44-68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow-up time of 489 days (281-812 days). The 1-, 2-, and 3-year mortality was 8% (95% CI, 6%-10%), 16% (95% CI, 13%-19%), and 21% (95% CI, 17%-25%), respectively. When stratified into low-, intermediate-, and high-risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment-naïve patients, initial combination therapy was associated with better 1-year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19-0.95]; P=0.037). Conclusions Mortality in the intermediate- and high-risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.

Keywords: United States; pulmonary hypertension; right ventricle; survival; vasodilators.

Figure 1. Study flow diagram.

CHD indicates congenital heart disease; COMPERA, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; CTD, connective tissue disease; CTEPH, chronic thromboembolic pulmonary hypertension; FPHR, French Pulmonary Hypertension Registry; HTN, hypertension; PAH, pulmonary arterial hypertension; PHAR, Pulmonary Hypertension Association Registry; PVOD, pulmonary veno‐occlusive disease; and REVEAL, The Registry to Evaluate Early and Long‐Term PAH Disease Management.

Figure 2. Kaplan‐Meier survival estimates in all PAH and idiopathic and heritable patients with PAH.

A, Mortality in all patients with PAH. B, Mortality in idiopathic and heritable patients with PAH. PAH indicates pulmonary arterial hypertension.

Figure 3. Mortality in all patients with PAH by risk categorization at baseline using Kaplan‐Meier survival analysis.

Data are presented as mean±SE measurement. COMPERA indicates Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; FPHR, French Pulmonary Hypertension Registry; PAH, pulmonary arterial hypertension; and REVEAL, The Registry to Evaluate Early and Long‐Term PAH Disease Management.

Figure 4. Kaplan‐Meier survival estimates based on initial treatment strategy in patients diagnosed with PAH ≤6 months.

Combo indicates initial combination therapy (dual and triple); HR, hazard ratio; Mono, initial monotherapy; and PAH, pulmonary arterial hypertension.

Figure 5. Mortality in idiopathic and heritable patients with PAH by risk categorization at baseline using Kaplan‐Meier survival analysis.

Data are presented as mean±SE measurement. COMPERA indicates Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; FPHR, French Pulmonary Hypertension Registry; PAH, pulmonary arterial hypertension; and REVEAL, The Registry to Evaluate Early and Long‐Term PAH Disease Management.