PURPOSE: The Registry to EValuate Early And Long-term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL) is a 54-center, observational, US-based study that providing information about demographics, course and management of patients with Group I PAH. Three year outcomes from time of REVEAL enrollment and 2-year major event-free survival from time of clinical worsening are presented.
METHODS: Major events were defined as death, transplant, or atrial septostomy. Clinical worsening was defined two ways: (A) New York Heart Association functional class (FC) worsening or 15% reduction in 6-minute walk test distance (6-MWD) and (B) any component of (A) or hospitalization for any reason or initiation of parenteral prostanoids. Major event free survival was evaluated in patients who did and did not experience A or B in the first year post-enrollment. Kaplan-Meier estimates are reported for all events.
RESULTS: 3012 adult patients with pulmonary capillary wedge pressure ≤15mmHg were enrolled from March 2006 through December 2009. Mean age at enrollment was 53 years; 7%, 34%, 52% and 7% were FC I, II, III, and IV, respectively. One-year freedom from worsening was 73.8±0.9% by definition (A) and 48.0±0.9% by (B). By definition A, 1582 patients were free from clinical worsening one year post-enrollment and 683 patients worsened; estimated subsequent 2-year survival was 95.2±0.7% versus 69.4±1.8%, respectively (P<0.001). By definition B, subsequent 2-year survival for non-worseners (n=1193) and worseners (n=1483) was 92.9 ± 1.0% and 70.7 ± 1.2%, respectively (P<0.001). From enrollment, 3-year survival was 75.1%±0.9% and freedom from major events was 72.9±0.9%.
CONCLUSION: Freedom from worsening through one year was associated with a well above average 2 year prognosis. Clinical worsening defined as A (worse FC or 6-MWD) appeared to more reliably predict major events than definition B.
CLINICAL IMPLICATIONS: This analysis clearly indicates that “softer” markers of clinical worsening are strongly associated with survival, making time to clinical worsening an important indicator of patient prognosis and a good proxy for mortality in clinical trial design.
DISCLOSURE: Adaani Frost, Grant monies (from industry related sources) Adaani E. Frost, MD, has received grants from Gilead and Actelion and grants to Baylor for IRB-approved research.Dr. Badesch has received grants from Actelion/CoTherix, Gilead/Myogen, Encysive Pharmaceuticals, Pfizer, United Therapeutics, Lung Rx, Eli Lilly & Co./ICOS, and NIH/NHLBI.Raymond L. Benza, MD, has received or is pending receipt of grants from Actelion, United Therapeutics, Gilead, and Lung Rx. Dr. McGoon has received grants from Gilead/Myogen and Medtronic.; Employee Dave P. Miller, MS, is employed by ICON Clinical Research, a company that receives research support from Actelion and other pharmaceutical companies; Consultant fee, speaker bureau, advisory committee, etc. Adaani E. Frost, MD, serves as a consultant for Gilead and Actelion. Dr. Frost has received honoraria from Gilead, Actelion, and Pfizer and has provided expert testimony on diet pill litigation. Dr. Frost has received honoraria for her service on the REVEAL Steering Committee, which is supported by Actelion.David B. Badesch, MD, has received honoraria for service on Steering Committees and/or Advisory Boards for Actelion/CoTherix, Gilead/ Myogen, Encysive Pharmaceuticals, Pfizer, GlaxoSmithKline, Lung Rx, United Therapeutics, Eli Lilly & Co./ICOS, Biogen Idec, and mondoBIOTECH. Dr. Badesch has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion. Raymond L. Benza, MD, has received honoraria from Actelion, United Therapeutics, and Gilead. Dr. Benza has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion. Michael McGoon, MD, serves as a consultant with Actelion/CoTherix, Gilead/Myogen, Lung Rx, and Medtronic. Dr. McGoon has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion.; No Product/Research Disclosure Information