Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

被引：17

作者：

Hoeper, Marius M. ^{[1
,2
]}

Gomez Sanchez, Miguel-Angel ^{[3
]}

Humbert, Marc ^{[4
]}

Pittrow, David ^{[5
]}

Simonneau, Gerald ^{[6
]}

Gall, Henning ^{[7
,8
]}

Gruenig, Ekkehard ^{[9
]}

Klose, Hans ^{[10
]}

Halank, Michael ^{[11
]}

Langleben, David ^{[12
]}

Snijder, Repke J. ^{[13
]}

Subias, Pilar Escribano ^{[14
]}

Mielniczuk, Lisa M. ^{[15
]}

Lange, Tobias J. ^{[16
]}

Vachiery, Jean-Luc ^{[17
]}

Wirtz, Hubert ^{[18
]}

Helmersen, Douglas S. ^{[19
]}

Tsangaris, Iraklis ^{[20
]}

Barbera, Joan A. ^{[21
,22
]}

Pepke-Zaba, Joanna ^{[23
]}

Boonstra, Anco ^{[24
]}

Rosenkranz, Stephan ^{[25
,26
]}

Ulrich, Silvia ^{[27
]}

Steringer-Mascherbauer, Regina ^{[28
]}

Delcroix, Marion ^{[29
,30
]}

Jansa, Pavel ^{[31
]}

Simkova, Iveta ^{[32
,33
]}

Giannakoulas, George ^{[34
]}

Klotsche, Jens ^{[35
]}

Williams, Evgenia ^{[36
]}

Meier, Christian ^{[36
]}

Ghofrani, Hossein-Ardeschir ^{[7
,8
]}

机构：

[1] Hannover Med Sch, Dept Resp Med, Hannover, Germany

[2] Hannover Med Sch, German Ctr Lung Res, Hannover, Germany

[3] Ramon Y Cajal Univ Hosp IRYCIS, Biomed Res Networking Ctr Resp Dis CIBERES, Resp Dept, Madrid, Spain

[4] Univ Paris Saclay, Serv Pneumol & Soins Intensifs Resp, Inserm U999, Hop Bicetre, Le Kremlin Bicetre, France

[5] Tech Univ, Inst Clin Pharmacol, Dresden, Germany

[6] Univ Paris Sud, Hop Bicetre, Serv Pneumol, Ctr Reference Hypertens Pulm Severe,DHU Thorax In, Paris, France

[7] Univ Giessen & Marburg Lung Ctr UGMLC, Giessen, Germany

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

[9] Thoraxclin Heidelberg Univ Hosp, Ctr Pulm Hypertens, Heidelberg, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Dept Pneumol, Hamburg, Germany

[11] Univ Hosp Carl Gustav Carus, Dept Pneumol, Med Clin 1, Dresden, Germany

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

[13] St Antonius Hosp, Dept Pulmonol, Nieuwegein, Netherlands

[14] Hosp 12 Octubre, Dept Cardiol, CIBER CV CIBER Cardiovasc Dis, Madrid, Spain

[15] Univ Ottawa, Dept Med, Div Cardiol, Heart Inst, Ottawa, ON, Canada

[16] Univ Med Ctr, Dept Internal Med 2, Div Pneumol, Regensburg, Germany

[17] Clin Univ Bruxelles, Hop Erasme, Dept Cardiol, Brussels, Belgium

[18] Univ Leipzig, Dept Resp Med, Leipzig, Germany

[19] Univ Calgary, Alberta Hlth Serv, Calgary, AB, Canada

[20] Natl & Kapodistrian Univ Athens, Univ Hosp Attikon, Dept Crit Care 2, Athens, Greece

[21] Univ Barcelona, Hosp Clin IDIBAPS, Barcelona, Spain

[22] Biomed Res Networking Ctr Resp Dis CIBERES, Madrid, Spain

[23] Royal Papworth Hosp, Pulm Vasc Dis Unit, Cambridge, England

[24] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

[25] Cologne Univ, Dept Internal Med 3, Heart Ctr, Cologne, Germany

[26] Cologne Univ, Cologne Cardiovasc Res Ctr CCRC, Heart Ctr, Cologne, Germany

[27] Univ Hosp Zurich, Clin Pulmonol, Zurich, Switzerland

[28] Krankenhaus Elisabethinen Linz GmbH, Servicestelle Klin Studien, Linz, Austria

[29] KU Leuven Univ Leuven, Univ Hosp, Clin Dept Resp Dis, Leuven, Belgium

[30] KU Leuven Univ Leuven, Lab Resp Dis & Thorac Surg BREATHE, Dept Chron Dis & Metab CHROMETA, Leuven, Belgium

[31] Charles Univ Prague, Dept Med 2, Dept Cardiovasc Med, Prague, Czech Republic

[32] Slovak Med Univ, Fac Med, Dept Cardiol & Angiol, Bratislava, Slovakia

[33] Natl Inst Cardiovasc Dis, Bratislava, Slovakia

[34] Aristotle Univ Thessaloniki, Dept Cardiol 1, Thessaloniki, Greece

[35] German Rheumatism Res Ctr Berlin, Leibniz Inst, Berlin, Germany

[36] Bayer AG, Global Dev, Global Med Affairs, Berlin, Germany

来源：

RESPIRATORY MEDICINE | 2021年 / 177卷

关键词：

Pulmonary arterial hypertension; Pulmonary hypertension; Riociguat; Registry; Clinical practice; Safety; LONG-TERM EXTENSION; OPEN-LABEL; OUTCOMES; PREDICTORS; SURVIVAL;

D O I：

10.1016/j.rmed.2020.106241

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms. Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH.

引用

页数：11

共 27 条

[1] Pulmonary Arterial Hypertension Baseline Characteristics From the REVEAL Registry [J].

Badesch, David B. ;

Raskob, Gary E. ;

Elliott, C. Greg ;

Krichman, Abby M. ;

Farber, Harrison W. ;

Frost, Adaani E. ;

Barst, Robyn. J. ;

Benza, Raymond L. ;

Liou, Theodore G. ;

Turner, Michelle ;

Giles, Scott ;

Feldkircher, Kathy ;

Miller, Dave P. ;

McGoon, Michael D. .

CHEST, 2010, 137 (02) :376-387

[2]

Bayer AG, 2018, ADEMPAS US PRESCRIBI

[3]

Bayer AG, ADEMPAS RIOCIGUAT TA

[4] Predicting Survival in Pulmonary Arterial Hypertension Insights From the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) [J].

Benza, Raymond L. ;

Miller, Dave P. ;

Gomberg-Maitland, Mardi ;

Frantz, Robert P. ;

Foreman, Aimee J. ;

Coffey, Christopher S. ;

Frost, Adaani ;

Barst, Robyn J. ;

Badesch, David B. ;

Elliott, C. Gregory ;

Liou, Theodore G. ;

McGoon, Michael D. .

CIRCULATION, 2010, 122 (02) :164-U138

[5] Five-Year Outcomes of Patients Enrolled in the REVEAL Registry [J].

Farber, Harrison W. ;

Miller, Dave P. ;

Poms, Abby D. ;

Badesch, David B. ;

Frost, Adaani E. ;

Muros-Le Rouzic, Erwan ;

Romero, Alain J. ;

Benton, Wade W. ;

Elliott, C. Gregory ;

McGoon, Michael D. ;

Benza, Raymond L. .

CHEST, 2015, 148 (04) :1043-1054

[6] The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension [J].

Gaine, Sean ;

Simonneau, Gerald .

EUROPEAN RESPIRATORY REVIEW, 2013, 22 (130) :487-494

[7] 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT) [J].

Galie, Nazzareno ;

Humbert, Marc ;

Vachiery, Jean-Luc ;

Gibbs, Simon ;

Lang, Irene ;

Torbicki, Adam ;

Simonneau, Gerald ;

Peacock, Andrew ;

Noordegraaf, Anton Vonk ;

Beghetti, Maurice ;

Ghofrani, Ardeschir ;

Gomez Sanchez, Miguel Angel ;

Hansmann, Georg ;

Klepetko, Walter ;

Lancellotti, Patrizio ;

Matucci, Marco ;

McDonagh, Theresa ;

Pierard, Luc A. ;

Trindade, Pedro T. ;

Zompatori, Maurizio ;

Hoeper, Marius .

EUROPEAN HEART JOURNAL, 2016, 37 (01) :67-+

[8]

Gall H., 2017, J HEART LUNG TRANSPL, pS1053

[9]

GHOFRANI HA, 2020, RESP MED

[10] Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial [J].

Ghofrani, Hossein-Ardeschir ;

Grimminger, Friedrich ;

Gruenig, Ekkehard ;

Huang, Yigao ;

Jansa, Pavel ;

Jing, Zhi-Cheng ;

Kilpatrick, David ;

Langleben, David ;

Rosenkranz, Stephan ;

Menezes, Flavia ;

Fritsch, Arno ;

Nikkho, Sylvia ;

Humbert, Marc .

LANCET RESPIRATORY MEDICINE, 2016, 4 (05) :361-371

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