The Relationship between Anticoagulation and Mortality in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry (PHAR)

Abstract

PurposeLong-term anticoagulation (AC) in pulmonary arterial hypertension (PAH) remains controversial, with prior cohorts reporting 28-66% of participants using AC. In idiopathic PAH (IPAH), AC is associated with improved survival or neutral effect, but may be detrimental in those with PAH from connective tissue disease (CTD-PAH). We sought to evaluate the relationship between AC use and mortality in PHAR, a multi-center prospective registry which enrolled patients referred to pulmonary hypertension care centers between 2015-2020.MethodsForty-seven centers collected clinical characteristics, including PAH-specific therapy and survival, at roughly 6month intervals. We compared participants who received AC at baseline to those who did not. We excluded participants <18 years old and with PAH from congenital heart disease. Mortality was assessed using Kaplan-Meier plots and cox regression analysis adjusted for age, sex, body mass index, race, center, mean pulmonary artery pressure, functional class, and use of PAH specific therapy.ResultsThere were 817 participants who met inclusion criteria. The cohort had a mean age of 56 years, 76% were female, 41% had a diagnosis of IPAH, and 34% had a diagnosis of CTD-PAH. Most participants, 85%, had WHO functional class II-III disease. Overall, 21% of participants were on AC at enrollment; 26% of those with IPAH and 17% of those with CTD-PAH. AC use decreased between 2015 to 2019, from 29% to 19%. Median AC duration was 31 months. AC was not associated with mortality in IPAH (adjusted HR 0.9; CI 0.4-1.9) or CTD-PAH (adjusted HR 1.0; CI 0.4 - 2.5) (Figure).ConclusionAC use in PAH has decreased over time, and is lower than prior registries. AC use is not associated with increased mortality in this analysis of the contemporary PHAR cohort. Analyses examining the relationship between AC use and health care utilization and quality of life are forthcoming. Long-term anticoagulation (AC) in pulmonary arterial hypertension (PAH) remains controversial, with prior cohorts reporting 28-66% of participants using AC. In idiopathic PAH (IPAH), AC is associated with improved survival or neutral effect, but may be detrimental in those with PAH from connective tissue disease (CTD-PAH). We sought to evaluate the relationship between AC use and mortality in PHAR, a multi-center prospective registry which enrolled patients referred to pulmonary hypertension care centers between 2015-2020. Forty-seven centers collected clinical characteristics, including PAH-specific therapy and survival, at roughly 6month intervals. We compared participants who received AC at baseline to those who did not. We excluded participants <18 years old and with PAH from congenital heart disease. Mortality was assessed using Kaplan-Meier plots and cox regression analysis adjusted for age, sex, body mass index, race, center, mean pulmonary artery pressure, functional class, and use of PAH specific therapy. There were 817 participants who met inclusion criteria. The cohort had a mean age of 56 years, 76% were female, 41% had a diagnosis of IPAH, and 34% had a diagnosis of CTD-PAH. Most participants, 85%, had WHO functional class II-III disease. Overall, 21% of participants were on AC at enrollment; 26% of those with IPAH and 17% of those with CTD-PAH. AC use decreased between 2015 to 2019, from 29% to 19%. Median AC duration was 31 months. AC was not associated with mortality in IPAH (adjusted HR 0.9; CI 0.4-1.9) or CTD-PAH (adjusted HR 1.0; CI 0.4 - 2.5) (Figure). AC use in PAH has decreased over time, and is lower than prior registries. AC use is not associated with increased mortality in this analysis of the contemporary PHAR cohort. Analyses examining the relationship between AC use and health care utilization and quality of life are forthcoming.