The Six Minute Walk Test (6MWT) correlates with mortality in PAH. NYHA functional class (FC) and 6MWT are used as endpoints and to guide individual patient therapy. 6MWT is fairly reproducible, FC is subjective in the mid-range (Classes II & III). In patient management, this subjectivity can impact therapy. In studies, endpoints might be impacted. Consistent functional classification is expected by the same observers assessing the same patients in these studies. Change in one assessment should theoretically be in the same direction as the other. In PAH studies, discrepancies have been observed . Our study aims to assess the sensitivity and specificity of a change in the 6MWT to predict a change in NYHA FC.
Data was derived from the STRIDE-1 study. 178 PAH patients were enrolled testing the safety and efficacy of Sitaxsentan. 6MWT and FC were recorded at baseline, 6 and 12 weeks. A change in 6MWT was defined >10% from baseline. Complete data was available on 168 patients.
45 patients had more than 10% improvement in their 6MWT, 19 improved their FC, none worsened, 26 did not change their FC. Sensitivity of a 10% and more change in 6MWT to predict FC improvement is 48% with a specificity of 73%. 31 patients had more than 10% deterioration in their 6MWT, 2 worsened their FC, 1 improved and 28 had no change in FC. Sensitivity of a 10% or more deterioration in 6MWT to predict FC deterioration is 66% with a specificity of 71%. 92 patients did not change their 6MWT more than 10%, 21 improved their FC, 1 worsened and 70 had no change in FC. Sensitivity of no change in 6MWT to predict no change in FC is 56% and a specificity of 50%.
Sensitivity and specificity of improvement, deterioration or no change in 6MWT was poor to predict a similar directional change in FC.
Modified or integrated endpoints may be needed to assess study outcomes and patient response to intervention. Improved FCWorse FCNo Change in FCImprovement > 10% in 6MWT19026Change within 10% in 6MWT21170Deterioration > 10% in 6MWT1228FC improved / YesFC improved / NoImprovement > 10% in 6MWT / Yes1926Sens = 48%Improvement > 10% in 6MWT / No2170Spec = 73%FC worsened / YesFC worsened / NoDeterioration > 10% in 6MWT / Yes228Sens = 66%Deterioration > 10% in 6MWT / No170Spec = 71%FC unchanged / YesFC unchanged / NoChange within 10% in 6MWT / Yes7022Sens = 76%Change within 10% in 6MWT / No5422Spec = 71%
N.Y. Hamzeh, Dr. Frost Received grants from Encysive