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Título

Effects of long-term calcium channel blocker therapy on patients with Idiopathic or Drug-Associated Pulmonary Arterial Hypertension: A systematic review and meta analysis

Resumo

Introduction
When discussing treatment options for patients with Idiopathic Pulmonary Arterial Hypertension (IPAH) or Drug/Toxin-Associated Pulmonary Arterial Hypertension (DPAH) with a positive Vasodilator Testing (VdT+), long-term Calcium Channel Blocker (CCB) therapy is known to be beneficial. However, this practice is based on limited evidence, mainly expert consensus, small-scale studies, retrospective analysis, and registries, such as guidelines from well-known Cardiology Societies.

Objectives
A meta-analysis was carried out aiming to evaluate the response to long-term CCB therapy in patients with IPAH or DPAH and a VdT+.

Methods
We searched PubMed, Embase, and Cochrane Library for both randomized and non-randomized studies. From the retrieved literature, the following primary outcomes of interest were identified: Mean Pulmonary Artery Pressure (mPAP), 6-minute Walk Distance (6MWD), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), and Mixed Venous Oxygen Saturation (SvO2), measured at the beginning and end of the selected studies. We also analyzed subgroups for the outcomes, dividing subjects into two age groups: ≤ 18 years old and > 18 years old. We used OpenMeta (Analyst) 12.11.14 for statistical analysis and the I² statistics tool to assess heterogeneity.

Results
We selected 7 non-randomized studies, involving 131 patients, with an average follow-up time of 2.74 (1.3) years. The mean values observed for individual outcomes in VdT+ patients treated with long-term CCB therapy are the following: mPAP (33.1 mmHg; 95% CI [31.6, 34.6]; I²=0%), 6MWD (470.1 m; 95% CI [452.6, 487.7]; I²=0%), CI (3.8 L/min/m²; 95% CI [3.6, 4.0]; I²=0%), mRAP (4.2 mmHg; 95% CI [3.6, 4.8]; I²=0%) and SvO₂ (73.9%; 95% CI [72.5, 75.3]; I²=0%). Additionally, we assessed baseline values and found the following means: mPAP (51.2 mmHg; 95% CI [49.3, 53.0]; I²=0%), 6MWD (428.4 m; 95% CI [410.3, 446.6]; I²=0%), Cardiac index (2.8 L/min/m²; 95% CI [2.7, 2.9]; I²=0%), mRAP (6.4 mmHg; 95% CI [5.6, 7.2]; I²=0%), and SvO₂ (68.5%; 95% CI [66.5, 70.5]; I²=0%).

Conclusion
The findings of our study suggests that, in patients with IPAH or DPAH who exhibit a VdT+, there is a positive effect of long-term CCB therapy in the evaluated hemodynamic parameters, CI and 6MDW test. The mentioned results align with the current recommended guidelines and reinforces their level of evidence.

Palavras Chave

Calcium channel blocker; Pulmonary hypertension; Treatment

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