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. 2022 Jul;41(7):971-981.
doi: 10.1016/j.healun.2022.03.011. Epub 2022 Mar 22.

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis

Marius M Hoeper  1 , Christine Pausch  2 , Karen M Olsson  3 , Doerte Huscher  4 , David Pittrow  5 , Ekkehard Grünig  6 , Gerd Staehler  7 , Carmine Dario Vizza  8 , Henning Gall  9 , Oliver Distler  10 , Christian Opitz  11 , J Simon R Gibbs  12 , Marion Delcroix  13 , H Ardeschir Ghofrani  14 , Ralf Ewert  15 , Harald Kaemmerer  16 , Hans-Joachim Kabitz  17 , Dirk Skowasch  18 , Juergen Behr  19 , Katrin Milger  20 , Michael Halank  21 , Heinrike Wilkens  22 , Hans-Jürgen Seyfarth  23 , Matthias Held  24 , Daniel Dumitrescu  25 , Iraklis Tsangaris  26 , Anton Vonk-Noordegraaf  27 , Silvia Ulrich  28 , Hans Klose  29 , Martin Claussen  30 , Stephan Eisenmann  31 , Kai-Helge Schmidt  32 , Stephan Rosenkranz  33 , Tobias J Lange  34
Affiliations
Free article

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis

Marius M Hoeper et al. J Heart Lung Transplant. 2022 Jul.
Free article

Abstract

Background: The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated.

Methods: Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses.

Results: All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools.

Conclusion: While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials.

Keywords: clinical trials; endpoints; mortality; pulmonary arterial hypertension; risk; treatment.

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