The Minimally Important Difference in the Six-minute Walk Test Predicts Clinical Worsening in Pulmonary Arterial Hypertension.

Background: The minimally important difference (MID) in the six-minute walk test (6MWT) for pulmonary arterial hypertension (PAH) is estimated to be 33 meters using distributional and anchor-based methods. Quality of life was used as the anchor. Here, we sought to determine whether the MID is predictive of clinical worsening.

Methods: This was a post hoc analysis of the pivotal clinical trial of tadalafil in PAH (n = 405) and its extension phase (n = 161). The 6MWT was determined at the end of the placebo-controlled phase of 16 weeks and dichotomized as < 33 or ≥ 33 meters. Primary outcome was clinical worsening ascertained at 16 weeks and at 68 weeks of follow up. Cox proportional hazard analysis was used to determine the association between 6MWT and clinical worsening.

Results: Mean age for patients in the pivotal trial of tadalafil was 54 years old (+/-15.5 yrs.). There were 317 (78.3%) female patients and 61% with idiopathic PAH. 53 % of the patients were on background bosentan therapy. A 6MWT < 33 meters was associated with an increased risk of clinical worsening at 16 and 68 weeks. These results were unchanged after adjusting for age, sex, background therapy with bosentan, and tadalafil dose. There were no PAH hospitalizations during short-term and long-term follow up in patients achieving a 6MWT ≥ 33 meters.

Conclusions: The 6MWT MID of 33 meters is predictive of short- and long-term clinical worsening. These results further validate 33 meters as a relevant MID for the 6MWT.