Medical Therapy Versus Balloon Angioplasty for CTEPH: A Systematic Review and Meta-Analysis

Background

A significant number of chronic thromboembolic pulmonary hypertension (CTEPH) patients will have an inoperable disease. Medical therapy and balloon pulmonary angioplasty (BPA) have provided alternate therapeutic options for patients with inoperable CTEPH, although there are a limited number of published studies examining the outcomes. Thus, our study aims to evaluate and compare the efficacy of medical therapy and BPA in patients with inoperable CTEPH.

Methods

An electronic search of six databases was performed and the search results were screened against established criteria for inclusion into this study. Data was extracted and meta-analytical techniques were used to analyse the data.

Results

Pooled data from RCTs revealed that medical therapy, compared with a placebo, was associated with a significant improvement of at least one functional class (p = 0.038). With regards to pulmonary haemodynamics, medical therapy also resulted in a significant reduction in both mean pulmonary arterial pressure (mPAP) (p = 0.002) and pulmonary vascular resistance (PVR) (p < 0.001). From the included observational studies, the 6-minute walk distance (6MWD) significantly increased following medical therapy by an average of 22.8% (p < 0.001). The pooled improvement in 6MWD was found to be significantly higher in the BPA group when compared to medical therapy for CTEPH (p = 0.001). Pooled data from available observational studies of medical therapy or BPA all demonstrated significant improvements in mPAP and PVR for pre versus post intervention comparisons. The improvement in mPAP (p = 0.002) and PVR (p = 0.002) were significantly greater for BPA intervention when compared to medical therapy.

Conclusions

High-quality evidence supports the use of targeted medical therapy in improving haemodynamics in patients with inoperable CTEPH. There is only moderate-quality evidence from observational studies supporting the efficacy of BPA in improving both haemodynamics and exercise capacity. Further RCTs and prospective observational studies comparing medical therapy and BPA in patients with inoperable CTEPH are required.

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1–4% of patients following an acute episode of pulmonary embolism [1], [2], [3], [4]. It is an under-diagnosed but severe condition due to chronic organisation of non-resolving thrombi within the pulmonary arteries, resulting in an elevation of pulmonary artery pressure and, ultimately, right heart failure, if left untreated [5], [6], [7]. CTEPH is haemodynamically defined by the presence of precapillary pulmonary hypertension (mean pulmonary artery pressure ≥25 mmHg and pulmonary artery wedge pressure ≤15 mmHg), together with the demonstration of obstructive lesions within the pulmonary arteries on imaging despite 3 months of anticoagulation [7], [8].

Pulmonary endarterectomy (PEA) is the preferred management strategy for patients with CTEPH who have disease amenable for surgery following assessment by a multidisciplinary CTEPH team [7], [8]. Although PEA is potentially curative and should be offered as first-line therapy for CTEPH [9], a significant number of CTEPH patients will have an inoperable disease, for reasons such as the predominance of distal lesions that are technically inaccessible by the surgeon, or the presence of severe medical co-morbidities that preclude surgery. In experienced CTEPH centres, up to 30–40% of patients are deemed to have an inoperable disease following multidisciplinary team evaluation [10], [11]. In addition, 15–30% of patients will have persistent or recurrent pulmonary hypertension following PEA [12], [13], [14]. Thus, there is an unmet need for efficacious therapies for patients with inoperable CTEPH.

A large number of efficacious agents targeting the prostacyclin, endothelin-1 and nitric oxide pathways are now approved for the treatment of pulmonary arterial hypertension (PAH) [15]. Due to similarities in the distal vasculopathy found in PAH and inoperable CTEPH, the use of targeted medical therapy has been explored for inoperable CTEPH. In clinical practice, “off-label” targeted medical therapies are used frequently despite the inconsistent data from both randomised and observational studies [16].

More recently, the novel technique of balloon pulmonary angioplasty (BPA) has provided a new therapeutic option for patients with inoperable CTEPH [17], [18]. Technical refinements of this technique have improved both its safety and efficacy, and current pulmonary hypertension guidelines have incorporated BPA in the management algorithm of inoperable CTEPH, despite the limited number of published studies [19].

The main aim of our study was to evaluate the available evidence of medical therapy and BPA in patients with inoperable CTEPH by performing a systematic review and meta-analysis of the available literature. An additional aim of our study was to compare the efficacy of medical therapy against BPA in patients with inoperable CTEPH.