Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: Insights from the REVEAL Registry

https://doi.org/10.1016/j.healun.2013.08.010Get rights and content

Background

Current guidelines recommend intravenous prostacyclin as first-line therapy for patients with pulmonary arterial hypertension (PAH) in New York Heart Association/World Health Organization functional class (FC) IV, or combination therapy for patients in any FC who do not respond to monotherapy. We investigated the aggressiveness of therapy in patients enrolled in the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) Registry who deteriorated to FC IV or died.

Methods

Among 3,515 patients (age ≥ 18 years) in REVEAL with a mean pulmonary artery pressure ≥ 25 mm Hg and pulmonary capillary wedge pressure ≤ 15 mm Hg, we examined three sub-sets: the 487 patients who had a PAH-related death, the larger set of 908 patients who died from any cause (PAH-related, not PAH-related, or unknown), and the 294 patients who were FC I, II, or III at enrollment and later assessed as FC IV.

Results

Among patients who died, 56% (n = 272 of 487) and 43% (n = 391 of 908) were receiving intravenous prostacyclin before death in the PAH-related death and all-cause death cohorts, respectively. In the PAH-related death cohort, 60% and 16% of patients were most recently assessed as FC III and IV, respectively; among those assessed as FC IV within 6 months of death, 57.7% (n = 15 of 26) had received intravenous prostacyclin. Because many patients died without an observed assessment of worsening to FC IV, we also evaluated medication use among the cohort of patients who worsened to FC IV during the study. One day before worsening to FC IV, 150 of 294 patients were not receiving intravenous prostacyclin and 70 were receiving only PAH-specific monotherapy; of these, 61% and 67%, respectively, received no additional therapy 90 days later.

Conclusions

Intravenous prostacyclin and combination therapy are not consistently used in the most seriously ill patients enrolled in REVEAL after being assessed as FC IV or at the time of death.

Section snippets

Study design

Study design and baseline characteristics of patients enrolled in REVEAL have been described previously.27, 28 Briefly, REVEAL is a 55-center (university-affiliated and community hospitals) observational, United States-based study.29 Patients are monitored for 5 years from the time of enrollment. Each participating center obtained Institutional Review Board approval before patient enrollment, and all patients provided informed consent. “Enrollment” was defined as the date consent was given.

Study population

Patient characteristics

At the data collection end point on September 15, 2011, 3,515 adult (aged ≥18 years) patients with PAH had been enrolled in REVEAL. Of these, 29% were newly diagnosed and 71% were previously diagnosed. Demographic characteristics of the PAH-related death, all-cause death, and FC worsening cohorts are reported in Table 1.

Discussion

These observations from REVEAL demonstrate that, despite current guideline recommendations, a substantial number of patients were not being treated as aggressively as guidelines suggest with intravenous prostacyclin and/or combination therapy at time of death and before or after being assessed as worsening to FC IV. A substantial number of patients were receiving only monotherapy at time of PAH-related death, and only 56% were receiving intravenous prostacyclin. The age-adjusted estimated

Disclosure statement

Assistance in manuscript development was provided by Jacqueline Lanoix, PhD, and Kathryn Leonard, of inScience Communications, Springer Healthcare. Ginny Lai, of ICON Late Phase & Outcomes Research, provided statistical programming support.

Funding and support for the REVEAL Registry were provided by Cotherix Inc, and its affiliate, Actelion Pharmaceuticals US Inc. Funding for preparation of this manuscript was provided by Actelion Pharmaceuticals US Inc.

H.W.F. serves as a consultant and is on

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