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Chest. 2013 Nov;144(5):1521-1529. doi: 10.1378/chest.12-3023.

Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis.

Author information

1
Baylor College of Medicine, Houston, TX. Electronic address: frost@bcm.tmc.edu.
2
University of Colorado Health Sciences Center, Denver, CO.
3
ICON Late Phase & Outcomes Research, San Francisco, CA.
4
Allegheny General Hospital, Pittsburgh, PA.
5
Actelion Pharmaceuticals US, Inc, South San Francisco, CA.
6
Mayo Clinic, Rochester, MN.

Abstract

BACKGROUND:

Time to clinical worsening has been proposed as a primary end point in clinical trials of pulmonary arterial hypertension (PAH); however, neither standardized nor validated definitions of clinical worsening across PAH trials exist. This study aims to evaluate a proposed definition of clinical worsening within a large prospective, observational registry of patients with PAH with respect to its value as a predictor of proximate (within 1 year) risk for subsequent major events (ie, death, transplantation, or atrial septostomy).

METHODS:

We assessed overall 2-year survival and survival free from major events to determine the relationship between clinical worsening and major events among adults with hemodynamically defined PAH (N = 3,001). Freedom from clinical worsening was defined as freedom from worsening functional class (FC), a ≥ 15% reduction in 6-min walk distance (6MWD), all-cause hospitalization, or the introduction of parenteral prostacyclin analog therapy.

RESULTS:

In the 2 years of follow-up, 583 patients died. Four hundred twenty-six died after a documented clinical worsening event, including FC worsening (n = 128), a ≥ 15% reduction in 6MWD (n = 118), all-cause hospitalization (n = 370), or introduction of a prostacyclin analog (n = 91). Patients who experienced clinical worsening had significantly poorer subsequent 1-year survival postworsening than patients who did not worsen (P < .001).

CONCLUSIONS:

Clinical worsening was highly predictive of subsequent proximate mortality in this analysis from an observational study. These results validate the use of clinical worsening as a meaningful prognostic tool in clinical practice and as a primary end point in clinical trial design.

TRIAL REGISTRY:

ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

PMID:
23907471
DOI:
10.1378/chest.12-3023
[Indexed for MEDLINE]

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