Six-minute walk distance (6MWD) and plasma B-type natriuretic peptide (BNP) are associated with outcome in pulmonary arterial hypertension (PAH); however their usefulness for individual prediction in patients is unknown. We studied the ability of 6MWD and plasma BNP before treatment and after 12 weeks of treatment to discriminate between high and low risk of death at 2 years.
383 patients received ambrisentan (ABS) treatment (2.5, 5, or 10mg once-daily) in a long-term study (ARIES-E). We generated receiver operating characteristic (ROC) curves using 6MWD (N=298) and plasma BNP (N= 249) data from patients who either died or had complete follow-up at two years. We assessed area under the ROC curve (AUC) and selected cut-points to maximize sensitivity and specificity.
In the overall population (N = 383), mean age was 51±15 years, 79% were female, 63% had idiopathic PAH, and the 2-year survival was 88%. 6MWD following 12 weeks of treatment was the best discriminator for 2-year survival (AUC = 0.82, 95% CI: 0.75 to 0.90), with a 6MWD of 350 m being the maximal cut-point for discrimination (sensitivity = 79%, specificity = 79%). A 12-week 6MWD ≥ 350 m predicted a 96% (95% CI: 92% to 98%) chance of 2-year survival (negative predictive value), whereas a 12-week 6MWD < 350 m predicted a 38% (95%CI: 29% to 49%) risk of death (positive predictive value). Baseline 6MWD, baseline BNP, and 12-week BNP had slightly lower AUCs (range: 0.77 to 0.78) and maximal cut-points were less apparent. Change from baseline in 6WMD or BNP (AUC = 0.59 and 0.57, respectively) performed worse than absolute 6MWD or BNP at baseline or at Week 12.
A 6MWD cut-point of 350 m following 12 weeks of ABS treatment reasonably discriminated between patients at high and low risk of death at 2 years.
In PAH patients, absolute 6WMD following short-term therapy may be a better indicator of long-term survival than the change from baseline.
Steven Kawut, University grant monies None; Grant monies (from sources other than industry) I have received NIH grant funding to perform a clinical trial in pulmonary arterial hypertension.; Grant monies (from industry related sources) I (or those in my department) have received grants for a CME conference and/or for clinical studies from Gilead Sciences, Actelion, Pfizer, United Therapeutics, and Lung Rx.; Consultant fee, speaker bureau, advisory committee, etc. I have served as a consultant, steering committee member, and/or speaker for Gilead Sciences, Actelion, Pfizer, Lilly, United Therapeutics, and Novartis.; Other Drs. Despain, Coar, and Dufton are employees of Gilead Sciences.; No Product/Research Disclosure Information