Dataset Information

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

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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC8426079 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRiociguat is a novel soluble guanylate cyclase stimulator, and has been widely used for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). Some studies found that riociguat had better effects on CTEPH and proved to be safe, but the results were not utterly consistent. Therefore, the purpose of this study was to comprehensively evaluate the efficacy and safety of riociguat in the treatment of CTEPH.MethodsRandomized controlled trials on riociguat for the treatment of CTEPH were searched through such electronic databases as PubMed, Embase, Cochrane Library, Web of Science, China national knowledge internet, and Wanfang. The outcomes included exercise capacity, pulmonary hemodynamics, and side effects. The fixed-effects or random-effects models were used to analyze the pooled data, and heterogeneity was assessed by the I2 test.ResultsFour studies involving 520 patients were included in this meta-analysis. Compared with the placebo group, riociguat significantly improved the hemodynamic indexes and increased 6-min walking distance (P < .0001, standardized mean difference (SMD) = -0.24, 95%CI -0.35 to -0.12; P < .00001, SMD = 0.52, 95%CI 0.33 to 0.71), and decreased the Borg dyspnea score (P = .002, SMD = -0.31, 95%CI -0.51 to -0.12). In addition, riociguat could also significantly reduce the living with pulmonary hypertension scores and increase the EQ-5D scores (P = .01, SMD=-0.23, 95%CI -0.42 to -0.05; P < .00001, SMD = 0.47, 95%CI 0.27 to 0.66), but there was no significant difference in the change level of N-terminal pro-hormone B-type natriuretic peptide in patients with riociguat (P = .20, SMD = -0.24, 95%CI -0.61 to -0.13). The common adverse events of riociguat were dyspepsia and peripheral edema, and no other serious adverse reactions were observed.ConclusionsWe confirmed that riociguat had better therapeutic effects in improving the hemodynamic parameters and exercise capacity in patients with CTEPH without inducing serious adverse events. This will provide a reasonable medication regimen for the treatment of CTEPH.

Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH). The disease is still underdiagnosed, and the true prevalence is unknown. CTEPH is characterized by intraluminal non-resolving thrombus organization and fibrous stenosis, or complete obliteration of pulmonary arteries, promoted by progressive remodeling of the pulmonary vasculature. One consequence of this is an increase in pulmonary vascular resistance and pressure, resulting in PH and progressive right heart failure, leading to death if left untreated. Endovascular disobliteration by pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients. PEA surgery is the only technique that can potentially cure CTEPH disease, especially in patients with fresh or organized thrombi of the proximal branches of pulmonary arteries. However, not all patients are eligible for PEA surgery. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) and targeted medical therapy as additional promising available treatments options for inoperable CTEPH and recurrent/persistent PH after PEA surgery. Studies on BPA have shown it to improve pulmonary hemodynamics, symptoms, exercise capacity and RV function in inoperable CTEPH. Subsequently, BPA has developed into an essential component of the modern era of CTEPH treatment. Large randomized controlled trials have demonstrated varying significant improvements with targeted medical therapy in technically inoperable CTEPH patients. Thus, treatment of CTEPH requires a comprehensive multidisciplinary assessment, including an experienced PEA surgeon, PH specialist, BPA interventionist and CTEPH-trained radiologist at expert centers. In this comprehensive review, we address the latest developments in the fast-evolving field of CTEPH. These include advancements in imaging modalities and developments in operative and interventional techniques, which have widened the range of patients who may benefit from these procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed. As the treatment options for CTEPH improve, hybrid management involving multiple treatments in the same patient may become a viable option in the near future.