How should a physician approach the pharmacological management of chronic thromboembolic pulmonary hypertension?

ABSTRACT

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the presence of organized thromboembolic material and proliferative fibrous intima occluding varying degrees of the pulmonary arteries, and is also accompanied by small vessel vasculopathy in occluded and non-occluded pulmonary vasculature. The similarity in hemodynamics and pathophysiology between CTEPH and group 1 pulmonary arterial hypertension provides the rationale for clinical use of pulmonary arterial hypertension (PAH)-specific therapy.

Areas covered

The authors present the current knowledge concerning the updated therapeutic strategies in CTEPH, and try to illustrate the established and uncertain role of PAH-specific therapy and anticoagulation therapy. The real-world observational registries and landmark randomized controlled trials of PAH-specific drugs in CTEPH are emphasized in the manuscript.

Expert opinion

Despite surgical and interventional therapies, which could provide effective and potential curable treatments, medical therapies are still the substantial and irreplaceable option for patients with CTEPH. More and more PAH-specific drugs have demonstrated favorable efficacy and safety profiles in patients with CTEPH. Additionally, anticoagulation therapy is also a substantial medical treatment in all CTEPH patients without contradiction. However, the benefit-to-risk balance in life-long anticoagulation and whether more individualized anticoagulation strategies are needed warrants further investigation.

KEYWORDS:

• Anticoagulation
• balloon pulmonary angioplasty
• chronic thromboembolic pulmonary hypertension
• pulmonary endarterectomy
• medical therapy
• riociguat

Article highlights

• PEA remains as the first choice for patients with CTEPH, particularly in those proximal lesion predominant cases. However, medical therapies, including PAH-specific therapy and anticoagulation are still the substantial options for patients with CTEPH.

• Up to now, riociguat is the only approved therapy for both inoperable CTEPH and residual PH after PEA.

• New RCTs are ongoing for new PAH-targeted medicine on those inoperable CTEPH and residual PH after surgery as well as bridging therapy before PEA or BPA.

• Long-term outcomes of PAH-specific therapy in inoperable CTEPH and residual PH after PEA are improved when compared to historical controls.

• Additionally, anticoagulation therapy is also a substantial medical treatment in all CTEPH patients without contradiction. Warfarin is still the first choice for anticoagulation in CTEPH.

This box summarizes key points contained in the article.

Declaration of interest

ZC Jing reports speaker fees from Bayer AG, Actelion, Pfizer Inc, and United Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee serves as a speaker and consultant for Bayer AG, Actelion and United Therapeutics. They are also an investigator on clinical trials sponsored by the above and also by Liquidia, Merck & Co, Gossamer and Respira. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was supported by the National Key Research and Development Program of China [2016YFC0901502], the CAMS Innovation Fund for Medical Sciences [2017-I2M-3-003], and the Capital Clinical Specialty Project of the Beijing Municipal [Z171100001017195 and Z181100001718203].