scholarly journals EXPRESS: Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension

2021 ◽  
pp. 204589402110073
Author(s):  
Nick H Kim ◽  
Demosthenes G. Papamatheakis ◽  
Timothy M. Fernandes
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Controlled Study ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Need To Evaluate ◽  
Thromboembolic Pulmonary Hypertension ◽  
Phosphodiesterase Type

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty [BPA] and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since AIR, the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week CHEST-1 study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multi-modality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

scholarly journals Methods of Pharmacological Treatment of Chronic Thromboembolic Pulmonary Hypertension Current Approaches to the Patients Management

Kardiologiia ◽  
2018 ◽  
Vol 58 (11) ◽  
pp. 82-93
Author(s):  
E. A. Ushkalova ◽  
S. K. Zyryanov ◽  
K. E. Zatolochina
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
The European Union ◽  
Pulmonary Thromboendarterectomy ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Thromboembolic Pulmonary Hypertension ◽  
Phosphodiesterase Type

In this paper we have discussed epidemiology, pathogenesis, and approaches to treatment of chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a unique potentially curable form of pulmonary hypertension. The gold standard of CTEPH treatment is pulmonary thromboendarterectomy. However, about 40% of patients with CTEPH are inoperable due to distal surgically inaccessible lesions of the pulmonary vasculature, severe hemodynamic impairments, or other contraindications. In addition, nearly half of patients have persistent or recurrent pulmonary hypertension following surgery. Current guidelines support the use of pharmacotherapy in these patients. In the article we have presented results of main clinical studies of targeted drugs therapy (endothelin receptor antagonists, prostanoids, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators) of patients with CTEPH. The only drug that has demonstrated robust clinical efficacy in terms of improvment hemodynamic parameters, exercise capacity and patients’ quality of life is the stimulator of the soluble guanylate cyclase riociguat. The efficacy and safety of riociguat have been investigated in short-term and long-term studies with follow-up up to 6 years. Results of these studies have constituted the basis forits approval by the regulatory authorities of more than 50 countries for the treatment of inoperable CTEPH and persistent or recurrent CTEPH after pulmonary thromboendarterectomy. In the European Union, USA and many other countries, riociguat is the only pharmacological agent approved for these indications.

scholarly journals Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial

2020 ◽  
Author(s):  
Ekkehard Grünig ◽  
Alison MacKenzie ◽  
Andrew J Peacock ◽  
Christina A Eichstaedt ◽  
Nicola Benjamin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Exercise Training ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Functional Class ◽  
European Countries ◽  
Walking Distance ◽  
Control Group ◽  
Randomized Controlled ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

Abstract Aims This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17–33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18–51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2  P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. Conclusion This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

scholarly journals Risk Factor Profiles Achieved with Medical Therapy in Prevalent Patients with Pulmonary Arterial and Distal Chronic Thromboembolic Pulmonary Hypertension

Respiration ◽  
2018 ◽  
Vol 96 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Philipp Bartenstein ◽  
Stéphanie Saxer ◽  
Paula Appenzeller ◽  
Mona Lichtblau ◽  
Esther I. Schwarz ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Risk Factor ◽  
Medical Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension

2003 ◽  
Vol 90 (09) ◽  
pp. 372-376 ◽  
Author(s):  
Diana Bonderman ◽  
Peter Turecek ◽  
Johannes Jakowitsch ◽  
Ansgar Weltermann ◽  
Christopher Adlbrecht ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
University Hospital ◽  
Clotting Factor ◽  
Controlled Study ◽  
Elevated Plasma ◽  
High Prevalence ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
One Year

SummaryChronic thromboembolic pulmonary hypertension (CTEPH) is an enigmatic disorder lacking signs, symptoms and classical risk factors for venous thromboembolism.The objective of the prospective case controlled study, carried out at the Pulmonary Hypertension Unit, University Hospital Vienna, Austria, was to investigate whether plasma FVIII is elevated in CTEPH patients.The study examined 122 consecutive patients diagnosed with CTEPH. Plasma FVIII was measured and compared with plasma FVIII of healthy controls (n=82) and of patients with non-thromboembolic pulmonary arterial hypertension (PAH, n=88).Results show that CTEPH patients had higher FVIII levels than controls (233±83IU/dl versus 123±40IU/dl, p<0.0001) and PAH patients (158±61IU/dl, p<0.0001). Plasma FVIII one year after surgery (212±94IU/dl) was statistically unchanged compared with preoperative values (FVIII: 226±88IU/dl, n=25). FVIII>230IU/dl was more prevalent in CTEPH patients (41%) than in controls (5%, p<0.0001) and PAH patients (22%, p=0.022).We can conclude that elevated plasma FVIII is the first prothrombotic factor identified in a large proportion of CTEPH patients.

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