Evidence base for specific pulmonary vasodilators in adults with congenital heart disease

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Abstract

After reviewing the current definitions and classification of pulmonary hypertension (PH) associated with congenital heart disease (CHD), based on an analysis of 59 clinical trials (of which 14 are randomized controlled trials) drugs registered in the Russian Federation, the evidence base for PH therapy in adults with CHD is provided. The presence of a randomized controlled trial of bosentan BREATHE-5 and uncontrolled trials of other drugs became the basis for a higher class and level of evidence of bosentan (IB) compared to other drugs (IIaC) for Eisenmenger syndrome in the current European (ERS/ESC 2015) and updated Russian (2020) guidelines. According to the updated European (ESC 2020) guidelines for congenital heart disease in adults, “in Eisenmenger patients with reduced exercise capacity (6MWT distance <450 m), a treatment strategy with initial endothelin receptor antagonist monotherapy should be considered followed by combination therapy if patients fail to improve (IIaB)”, “in low- and intermediate-risk patients with repaired simple lesions and pre-capillary PH, initial oral combination therapy or sequential combination therapy is recommended and high-risk patients should be treated with initial combination therapy including parenteral prostanoids (IA)” and “endothelin receptor antagonists and phosphodiesterase 5 inhibitors may be considered in selected patients with elevated pulmonary pressure/resistance in the absence of elevated ventricular end diastolic pressure (IIbC)”. Only three (bosentan, macitentan and selexipag) out of seven specific pulmonary vasodilators registered in the Russian Federation have indications for “pulmonary arterial hypertension associated with congenital heart disease and Eisenmenger syndrome” or “pulmonary arterial hypertension associated with corrected simple congenital heart disease” in the instructions for use.

About the authors

Anton A. Shmalts

Bakulev National Medical Research Center of Cardiovascular Surgery; Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: shmaltzanton@inbox.ru
ORCID iD: 0000-0001-8937-1796

д-р мед. наук, вед. науч. сотр. отд-ния хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «НМИЦ ССХ им. А.Н. Бакулева», доц. каф. сердечно-сосудистой хирургии ФГБОУ ДПО РМАНПО

Russian Federation, Moscow; Moscow

Sergey V. Gorbachevsky

Bakulev National Medical Research Center of Cardiovascular Surgery; Russian Medical Academy of Continuous Professional Education

Email: shmaltzanton@inbox.ru
ORCID iD: 0000-0002-4193-3320

д-р мед. наук, проф., зав. отд-нием хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «НМИЦ ССХ им. А.Н. Бакулева», проф. каф. сердечно-сосудистой хирургии ФГБОУ ДПО РМАНПО

Russian Federation, Moscow; Moscow

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2. Fig. 1. Classification of pulmonary hypertension (PH) associated with congenital heart defects (CHD) (based on the materials from the VI World Symposium on PH, Nice, 2018) [6, 10, 11].

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