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Pulmonary Vascular Disease |

Are Currently Recommended Treatment Goals Predictive of Long Term Survival in Pulmonary Arterial Hypertension Patients?

Gustavo Heresi, MD; Youlan Rao, PhD
Author and Funding Information

Cleveland Clinic, Cleveland, Ohio, Cleveland, OH


Chest. 2015;148(4_MeetingAbstracts):932A. doi:10.1378/chest.2274654
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Abstract

SESSION TITLE: Predictors of Outcomes in PAH

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 27, 2015 at 08:45 AM - 10:00 AM

PURPOSE: The 5th World Symposium recommended specific treatment goals for pulmonary arterial hypertension (PAH) patients: modified WHO functional class I or II, 6-minute walk distance (6MWD) ≥ 380 to 440 meters, normal natriuretic peptide levels, and normal right-sided invasive hemodynamics (right atrial pressure [RAP] < 8 and cardiac index [CI] > 2.5 to 3). However, only limited prospective data in idiopathic PAH support this recommendation. Our aim was to test these goals in a large group 1 PAH cohort against long term survival

METHODS: We analyzed the PHIRST and TRIUMPH populations. The predictor variables were WHO functional class, 6MWD, NT-pro-BNP levels and hemodynamics measured at the end of the placebo-controlled treatment phase (16 and 12 weeks, respectively). The primary outcome was all-cause mortality at the end of follow up during the open label extension phase. We compared groups that did or did not meet treatment goals via Kaplan-Meier curves and log-rank tests.

RESULTS: Baseline characteristics of the combined study population (n=563): age 53.5 ± 14.7 years, female sex 79%, idiopathic PAH 60.2%, PAH associated with connective tissue disease 25.6%, 6MWD 347 ± 71.7 meters, WHO class II 20.1% and class III 77.8%. There were 73 deaths, and the median time to death or to the end of the follow-up period was 1,000 days (range 3 to 2,066 days). Better survival was associated with follow up WHO functional class I or II (p=0.0013), 6MWD ≥ 380 meters (p<0.0001), or both (p=0.0006). Improving (from baseline) functional class was not predictive of survival, while improving 6MWD was, but the latter association was not as significant (p=0.04) as for the absolute value at follow up. In a subset of 85 PHIRST patients with hemodynamic data available, follow up CI > 2.5 L/min/m2 was marginally associated with better survival (p=0.046), but RAP < 8 was not (p=0.99). In a subset of 188 TRIUMPH patients with NT-pro-BNP data available, a normal NT-pro-BNP level (< 400 pg/mL) at follow up was not associated with survival (p=0.24).

CONCLUSIONS: WHO functional class I or II, 6MWD ≥ 380 meters and CI >2.5 L/min/m2 measured 12-16 weeks after the introduction of PAH targeted therapy are associated with better long-term survival in PAH. NT-pro-BNP levels and change in functional class are not predictive of long term survival in this data analysis.

CLINICAL IMPLICATIONS: These data support the use of absolute levels of functional class, 6MWD and CI measured during follow up as treatment goals for PAH patients.

DISCLOSURE: Gustavo Heresi: Consultant fee, speaker bureau, advisory committee, etc.: Bayer Healthcare, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics Youlan Rao: Employee: United Therapeutics

No Product/Research Disclosure Information


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