Comparative Efficacy and Safety of Targeted Therapies for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Network Meta-Analysis

Can Respir J. 2021 Sep 1:2021:1626971. doi: 10.1155/2021/1626971. eCollection 2021.

Abstract

Background: There is significant controversy relating to whether chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with pulmonary arterial hypertension- (PAH-) targeted therapies and which therapy is the optimal choice for patients. A large number of randomized controlled trials (RCTs) have compared PAH-targeted therapies with placebo or conventional therapies. In this study, we aimed to compare all of the PAH-targeted medications that are used to treat CTEPH and rank their efficacy by the application of network meta-analysis (NMA).

Methods: We searched PubMed, EMBASE, Web of Science, the Cochrane Central Register, https://clinicaltrials.gov, and who.int/trialsearch/, for relevant RCTs published up to January 2020. In addition to traditional meta-analysis, we also performed NMA in our systematic review, as deployed in a previous protocol (PROSPERO: CRD42020173765).

Results: Our study identified eight eligible RCTs that evaluated seven PAH-targeted therapies in 703 patients with CTEPH. NMA revealed that riociguat was ranked first as the most optimized therapy for ameliorating the 6-minute walk distance with a probability of 80.4%. Bosentan was significantly better than others with regard to reducing brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide with a probability of 84.3%. Sildenafil was identified as the best drug in terms of improving the New York Heart Association/World Health Organization functional class with a probability of 87.3%. Treprostinil and macitentan were more beneficial than other drugs in reducing pulmonary vascular resistance and lowering the incidence of clinical worsening with probabilities of 86.2% and 79.2%, respectively.

Conclusion: Analysis revealed positive advantages for the use of PAH-targeted drugs in patients with CTEPH. Overall, treprostinil and riociguat were superior to all other PAH-targeted medications in most of the outcomes investigated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Bosentan / therapeutic use*
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Natriuretic Peptide, Brain
  • Network Meta-Analysis
  • Sildenafil Citrate / therapeutic use*
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use*

Substances

  • Antihypertensive Agents
  • Vasodilator Agents
  • Natriuretic Peptide, Brain
  • Sildenafil Citrate
  • Bosentan