Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:317

Article

Benza, Raymond L.¹  Corris, Paul A.²  Klinger, James R.³  Langleben, David^4,5  Naeije, Robert⁶  Simonneau, Gerald^7,8  Ghofrani, Hossein-Ardeschir^9,10,11,12  Jansa, Pavel¹³  Rosenkranz, Stephan^14,15  Scelsi, Laura¹⁶  Thenappan, Thenappan¹⁷  Raina, Amresh¹⁸  Meier, Christian¹⁹  Busse, Dennis²⁰  Hoeper, Marius M.^21,22 

[1] Ohio State Univ, Wexner Med Ctr, Div Cardiovasc Med, 473 W 12th Ave,Suite 200, Columbus, OH 43210 USA

[2] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[3] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Div Pulm Sleep & Crit Care Med, Providence, RI 02903 USA

[4] McGill Univ, Jewish Gen Hosp, Ctr Pulm Vasc Dis, Montreal, PQ, Canada

[5] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

[6] Erasme Univ Hosp, Dept Cardiol, Brussels, Belgium

[7] Univ Paris Sud, Hop Bicetre, AP HP,Serv Pneumol, Lab Excellence Rescherche Medicament & Innovat Th, Le Kremlin Bicetre, France

[8] INSERM, Unite 999, Le Kremlin Bicetre, France

[9] Univ Giessen, Giessen, Germany

[10] Marburg Lung Ctr, Giessen, Germany

[11] German Ctr Lung Res DZL, Giessen, Germany

[12] Imperial Coll London, Dept Med, London, England

[13] Charles Univ Prague, Clin Dept Cardiol & Angiol, Fac Med 1, Dept Med 2, Prague, Czech Republic

[14] Univ Cologne, Ctr Mol Med Cologne CMMC, Clin Internal Med Cardiol 3, Cologne, Germany

[15] Univ Cologne, Cologne Cardiovasc Res Ctr CCRC, Cologne, Germany

[16] Fdn Ist Ric & Cura Carattere Sci Policlin S Matte, Div Cardiol, Pavia, Italy

[17] Univ Minnesota, Div Cardiol, Minneapolis, MN USA

[18] Allegheny Gen Hosp, Cardiovasc Inst, Pittsburgh, PA 15212 USA

[19] Bayer AG, Berlin, Germany

[20] Chrestos Concept GmbH & Co KG, Essen, Germany

[21] Hannover Med Sch, Clin Resp Med, Hannover, Germany

[22] German Ctr Lung Res DZL, Hannover, Germany

关键词: Riociguat;    Switching to riociguat;    Right heart function;    Biomarkers;    Pulmonary arterial hypertension;    Pulmonary hemodynamics;   

DOI  :  10.1016/j.ijcard.2020.05.044

来源: Elsevier

【 摘 要 】

Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and >= 30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

【 授权许可】

Free