Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension

Ghofrani, Hossein Ardeschir; D’Armini, Andrea Maria; Grimminger, Friedrich; Hoeper, Marius M.; Jansa, Pavel; Kim, Nick H.; Mayer, Eckhard; Simonneau, Gérald; Wilkins, Martin R.; Fritsch, Arno; Neuser, D; Weimann, G; Wang, Chen

doi:10.1056/nejmoa1209657

Cited by 1,150 publications

(998 citation statements)

References 32 publications

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“…In a randomized trial, riociguat significantly improved 6-minute walking distance, pulmonary vascular resistance, and other clinical outcomes in patients with CTEPH. 7) Its impact on acute exacerbation and survival in patients with CTEPH, however, remains unknown, and its clinical efficacy and survival benefit remain to be tested in a randomized controlled trial.…”

Section: Discussionmentioning

confidence: 99%

Rescue Balloon Pulmonary Angioplasty Under Veno-Arterial Extracorporeal Membrane Oxygenation in a Patient With Acute Exacerbation of Chronic Thromboembolic Pulmonary Hypertension

et al. 2015

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SummaryWe describe a case of a 41-year-old woman with acute exacerbation of chronic thromboembolic pulmonary hypertension (CTEPH) complicated by rapidly progressive respiratory failure and right heart failure with cardiogenic shock. A computed tomography (CT) showed thrombi in the right main pulmonary artery and bilateral peripheral pulmonary arteries, and echocardiography showed right ventricular dilatation and tricuspid regurgitation, with an estimated pressure gradient of 80 mmHg. The patient was initially diagnosed with acute pulmonary thromboembolism, and thrombolytic therapy was administered. Her condition subsequently deteriorated, however, necessitating mechanical ventilation and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We performed emergency catheter-directed thrombectomy and thrombus aspiration. Pulmonary hypertension (PH) temporarily improved, but subsequently worsened, and the patient was diagnosed with CTEPH. Pulmonary endarterectomy (PEA) was performed. After PEA, we were unable to wean the patient off VA-ECMO, and rescue balloon pulmonary angioplasty (BPA) to the middle and inferior lobe branches of the right lung was performed. Five days after BPA, the patient was removed from VA-ECMO and on the 57th day of hospitalization, she was weaned off the ventilator. The patient was discharged after 139 days of hospitalization. Rescue BPA represents a useful intervention for improving PH and weaning off VA-ECMO in a patient with acute exacerbation of CTEPH. (Int Heart J 2015; 56: 116-120) Key words: Right heart failure, Pulmonary endarterectomy, BPA, ECMO, CTEPH C hronic thromboembolic pulmonary hypertension (CTEPH) is caused by organized pulmonary thrombosis, and is considered to progress, at least in part, from acute pulmonary thromboembolism, though the exact etiology remains unknown. Five-year survival rates in patients with a mean pulmonary artery pressure (PAP) less than 30 mmHg is approximately 90%; a mean PAP over 50 mmHg confers a survival rate of approximately 10%, and very poor prognosis.1) Pulmonary endarterectomy (PEA) in patients with CTEPH can markedly decrease PAP and improve prognosis. 2)In peripheral types of CTEPH, however, PEA is ineffective and associated mortality rates are high. Recently, the efficacy of balloon pulmonary angioplasty (BPA) in inoperable CTEPH patients was reported.3) We successfully employed BPA under veno-arterial extracorporeal membrane oxygenation (VA-EC-MO) in a patient with acute exacerbation of CTEPH that did not improve with PEA. Case ReportA 41-year-old woman presented at our hospital with dyspnea, edema, and weight gain. She had suffered from epilepsy since the age of 16, and at 36 had exhibited multiple lacunar infarctions on magnetic resonance imaging (MRI). She was a heavy smoker (40 cigarettes per day for 20 years), but had no family history of thromboembolic disease or blood coagulation disorders. She was taking phenytoin 100 mg tid, valproic acid 400 mg qid, and aspirin 100 mg sid.On admission, her blood pressure was 102/58 mmHg...

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Section: Discussionmentioning

confidence: 99%

Rescue Balloon Pulmonary Angioplasty Under Veno-Arterial Extracorporeal Membrane Oxygenation in a Patient With Acute Exacerbation of Chronic Thromboembolic Pulmonary Hypertension

et al. 2015

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“…The CHEST study included 261 patients with inoperable CTEPH or with persistent/recurrent pulmonary hypertension after PEA, treated with Riociguat or placebo for 16 weeks (CHEST-1), followed by an open trial (CHEST-2). After 16 weeks, the 6 minute walking test signifi cantly increased by 46 meters (primary endpoint), and also the secondary endpoints NT-proBNP, PVR and WHO-class improved signifi cantly [19]. This agent subsequently to the positive results of the trial has been licensed as the fi rst specifi c medical treatment for non-operable CTEPH and for persistent pulmonary hypertension after PEA.…”

Section: Medical Treatmentmentioning

confidence: 99%

Chronic thromboembolic pulmonary hypertension - a diagnostic and therapeutic update

Stricker

2016

Vasa

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Summary:Chronic thromboembolic pulmonary hypertension (CTEPH), an important cause of severe pulmonary hypertension, is still underdiagnosed, mainly due to the insuffi cient use of V/Q scannning in patients with pulmonary hypertension. This article reviews the current diagnostic approach and discusses the therapeutic options in this particular form of pulmonary hypertension. Every patient with CTEPH should undergo an evaluation in a specialised centre with experience in pulmonary arterial endarteriectomy (PEA) as the potentially curative surgical technique. Partly unresolved questions regard the status of the recently described percutaneous transluminal pulmonary angioplasty and the best medical treatment in patients with inoperable or recurrent/persistent pulmonary hypertension after PEA.

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“…Riociguat was generally well tolerated in both the PATENT and CHEST studies, and safety and tolerability results for all 4 studies have been published previously. 10,11,17,18 In summary, the most common adverse events were headache, dyspepsia, peripheral edema, nausea, dizziness, diarrhea, nasopharyngitis, and vomiting. Drug-related serious adverse events were reported in 2.4% of patients receiving riociguat 2.5 mg 3 times daily in PATENT-1 and in 3.5% of patients receiving riociguat in CHEST-1.…”

Section: Phase 3 Trialsmentioning

confidence: 99%

Effects of Age and Sex on the Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat (BAY 63‐2521)

et al. 2016

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Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). This randomized, double-blind, placebo-controlled study investigated the pharmacokinetics of riociguat and its metabolite M1 in young (18-45 years) and elderly (64.5-80 years) healthy volunteers of both sexes to assist planning of the dose regimens for clinical trials. The data were also used to draw comparisons with the effects of age and sex on riociguat pharmacokinetics in patients with PAH and CTEPH from the riociguat phase 3 trials, PATENT and CHEST. Volunteers received an oral dose of either riociguat 2.5 mg or placebo, and the concentrations of riociguat and M1 in blood and urine samples were determined using mass spectrometry. In elderly healthy volunteers, overall riociguat and M1 exposure tended to be higher than in young healthy volunteers (P > 0.05), partly because of reduced renal clearance (approximately 28% reduction) and differences in body weight. Although the mean maximum concentrations of riociguat and M1 were significantly higher in women than in men (35% and 50% higher, respectively), total exposure was similar. Despite differences in riociguat and M1 pharmacokinetics, riociguat was well tolerated with a comparable safety profile across all subgroups, suggesting that differences in drug exposure due to age or sex were not sufficient to warrant a dose adjustment in clinical trials. Furthermore, similar pharmacokinetics were observed in patients with PAH and CTEPH. However, particular care should be exercised during individual dose titration of riociguat in elderly patients.

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Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension

Cited by 1,150 publications

References 32 publications

Rescue Balloon Pulmonary Angioplasty Under Veno-Arterial Extracorporeal Membrane Oxygenation in a Patient With Acute Exacerbation of Chronic Thromboembolic Pulmonary Hypertension

Rescue Balloon Pulmonary Angioplasty Under Veno-Arterial Extracorporeal Membrane Oxygenation in a Patient With Acute Exacerbation of Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension - a diagnostic and therapeutic update

Effects of Age and Sex on the Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat (BAY 63‐2521)

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