Calcium Channel Blockers in Non-responders to Vasoreactivity Testing in Pulmonary Arterial Hypertension: A Literature Review

Abstract

Background: In pulmonary arterial hypertension (PAH), high-dose calcium channel blockers (CCBs) are appropriate for selected patients who demonstrate acute vasoreactivity and maintain a favourable response. Their inappropriate use in non-responders may cause haemodynamic deterioration and delay effective treatment. Objective: To review the rationale and criteria for vasoreactivity testing, risks associated with CCB treatment in non-responders, available therapeutic alternatives, and relevant European and American recommendations. Methods: This narrative review considers the observational evidence, pivotal therapeutic trials, and guideline documents discussed in the manuscript, including the 2022 ESC/ERS guidelines, 2019 CHEST update, and 2009 ACCF/AHA expert consensus. Findings: A positive acute response requires a reduction in mean pulmonary arterial pressure of at least 10 mmHg to 40 mmHg or less, with unchanged or increased cardiac output. Acute responsiveness does not invariably predict sustained clinical benefit, making early and continuing reassessment necessary. For non-responders, therapeutic approaches include endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin pathway agents, and risk-adapted combination therapy. Sotatercept represents an additional treatment option for selected patients receiving background therapy. The European and American frameworks consistently discourage CCB monotherapy in non-responders, although their approaches to risk assessment differ. Conclusion: Distinguishing acute vasoreactivity from sustained treatment response is essential to avoiding inappropriate CCB use and guiding timely, individualised PAH management.