Long-standing response to calcium channel blocker therapy on patients with various types of pulmonary hypertension: a systematic review and meta analysis

Abstract

Abstract Background It is widely acknowledged that the extended use of calcium channel blocker (CCBs) therapy in patients diagnosed with Idiopathic Pulmonary Arterial Hypertension (IPAH), Heritable Pulmonary Arterial Hypertension (HPAH), or Drug- or Toxin-Associated Pulmonary Arterial Hypertension (DPAH) who exhibit a positive acute vasoreactivity test (VdT+) provides benefits to patients. However, this practice is supported by a limited body of evidence in the scientific literature, mainly derived from expert consensus and/or small-scale studies, retrospective analyses, and registries, as per the European Society of Cardiology (ESC) guidelines. Objectives We performed a meta-analysis to evaluate the long-standing response to CCBs in patients diagnosed with various forms of pulmonary hypertension. Design We conducted searches in PubMed, Embase, and Cochrane to select both randomised and non-randomised studies. The primary outcomes of interest identified were 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 studies. Additionally, we performed subgroup analyses for all outcomes based on age groups: ≤18 years and >18 years. Statistical analysis was carried out using OpenMeta[Analyst] 12.11.14, and heterogeneity was assessed using I² statistics. Results We identified 7 non-randomised studies comprising a total of 131 patients with an average follow-up duration of 2.74 (1.3) years. The following are the mean values observed for individual outcomes: mPAP (33.1 mmHg; 95% CI [31.6, 34.6]; p < 0.001; I²=0%), 6MWD (470.1 m; 95% CI [452.6, 487.7]; I²=0%), Cardiac index (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%) in patients with positive acute vasoreactivity test (VdT+) treated long-term with CCBs. Additionally, at study initiation, we 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 from this meta-analysis suggest that in VdT+ patients, the means of certain haemodynamic parameters with long-standing use of CCBs are similar or nearly similar to those of patients without any subtype of PAH. These results align with current guidelines and reinforce their level of evidence.