Efficacy of pharmacological therapies in reducing outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy: a systematic review and meta-analysis

AIMS: Significant advancements have been made in the management of obstructive hypertrophic cardiomyopathy (oHCM), yet the extent of left ventricular outflow tract (LVOT) gradient reduction achieved with commonly used pharmacological therapies [beta-blockers (BBs), calcium channel blockers (CCBs), disopyramide, and cardiac myosin inhibitors (CMIs)] relative to each other is still unclear. METHODS AND RESULTS: PubMed and Scopus were searched up to September 2024. Clinical trials or observational studies that assessed the changes associated with BBs, CCBs, disopyramide, or CMIs in LVOT gradient at rest or with provocation in patients with oHCM were included. Mean changes in LVOT gradients were pooled as mean differences (MD) with 95% confidence intervals (CIs) in a random-effects model. Thirty-seven studies, with 44 arms and 1898 patients, were included in the analysis. At the therapeutic class level, pooled analysis showed that disopyramide was associated with the highest reduction in LVOT gradient at rest [MD: -43.5 (95% CI, -51.6 to -35.3)], followed by CMIs [MD: -34.8 (95% CI, -40.6 to -29.0)], BBs [MD: -20.7 (95% CI, -29.4 to -12.0)], and then CCBs [MD: -14.7 (95% CI, -23.3 to -6.1)], inter-action P < 0.01. Within CMIs, mavacamten had a higher effect than aficamten on gradient reduction; among the included BBs, metoprolol showed the highest gradient reduction, while among CCBs, verapamil was the most effective (inter-action P < 0.01). Similar results were observed for provocable LVOT gradients. CONCLUSION: Pharmacological therapies effectively reduced LVOT gradients in oHCM patients to varying degrees, with disopyramide and CMIs showing the highest effect, followed by BBs and CCBs.