Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR)

https://doi.org/10.1016/j.healun.2022.08.019Get rights and content

Background

Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH.

Methods

The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL

Results

Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09).

Conclusions

Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

Section snippets

The pulmonary hypertension association registry (PHAR)

Characteristics of the PHAR, including rationale, criteria for enrollment, data collection procedures, and organizational structure have been described previously.20 The PHAR IRB approval is maintained at The University of Pennsylvania (Protocol Number 822830), which serves as single IRB. All patients provided informed consent for enrollment. Patients new to care at PHAR-associated pulmonary hypertension (PH) centers were non-consecutively enrolled beginning in 2015. The dataset analyzed in

Patient characteristics

There were 1175 patients that met inclusion criteria, with 316 patients anticoagulated during enrollment (Figure 1). The median duration of follow up was 839 days. Of the 540 patients with IPAH/HPAH, 176 (32.6%) were treated with anticoagulation and of the 389 patients with CTD-PAH, 91 (25.7%) were treated with anticoagulation. There were 638 patients (54.3%) that were diagnosed with PAH within 6 months of enrollment and therefore considered incident cases.

In the overall cohort, patients who

Discussion

In a large, multicenter, contemporary cohort, we found no association between mortality and anticoagulation treatment. Anticoagulation was consistently associated with increased healthcare utilization for the overall cohort, IPAH/HPAH subgroup, and the CTD-PAH subgroup in our primary analysis. These findings were durable on sensitivity analysis by anticoagulation definition for the overall cohort and CTD-PAH subgroup, but inconsistent for the IPAH/HPAH subgroup. This inconsistency suggests that

Conclusions

Anticoagulation may not have a role as routine therapeutic intervention in PAH. Anticoagulation does not reduce mortality and is associated with increased healthcare utilization with a signal to suggest a neutral or negative effect on QoL. Although early cohorts of PAH patients previously reported clinical mortality benefit to anticoagulation with a plausible physiologic hypothesis to support the findings, modern clinical cohorts such as the PHAR have not borne out a clear benefit.

Author contributions

JDG, NAK, and TDM conceived of the study. JDG, NAK, RK, TT, AH, DG, TB, MC, EH, MAS, and TDM participated in study design. JDG and RK performed statistical analysis. JDG wrote the first draft of the manuscript and NAK, RK, TT, AH, DG, TB, MC, EH, MAS, and TDM contributed to revising the manuscript. All authors have approved the final draft of the manuscript.

Financial Disclosure Statement

N.A.K. reports consulting fees from United Therapeutics, Janssen, and Acceleron and serves on advisory board for United Therapeutics, Janssen, and Bayer. R.K. reports grant support from the Pulmonary Hypertension Association. T.T. reports grant support from United Therapeutics, Aria CV, Acceleron Pharma, and Tenax Therapeutics, consulting fees from Acceleron Pharma, Altavant science, United Therapeutics, and Actelion, and serves on advisory board for Acceleron Pharma, Altavant science, United

Funding Sources

None

Acknowledgments

The Pulmonary Hypertension Association Registry (PHAR) is supported by Pulmonary Hypertension Care Centers, Inc., a supporting organization of the Pulmonary Hypertension Association. The authors thank the other investigators, the staff, and particularly participants of the PHAR for their valuable contributions. A full list of participating PHAR sites and institutions can be found at www.PHAssociation.org/PHAR.

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