Estimated Number Needed to Treat with Mavacamten vs Placebo to Improve Functional Capacity and Left Ventricular Outflow Tract Obstruction in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy

Introduction: Mavacamten improved functional capacity and LVOT obstruction in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in the EXPLORER-HCM study (NCT03470545). Objective: To determine the number needed to treat (NNT) to achieve a clinical response comparing 30-week treatment with mavacamten versus placebo in patients with symptomatic oHCM. Methods: Data from the EXPLORER-HCM trial were analyzed. Most patients (92%) were receiving beta-blockers or calcium channel blockers. Responses were assessed using several measures: primary efficacy endpoint (improvement of ≥1.5 mL/kg/min in pVO 2 and improvement of ≥1 NYHA class or improvement of ≥3.0 mL/kg/min in pVO 2 and no worsening in NYHA class); symptoms (NYHA class); PROs (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ CSS] and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath [HCMSQ SoB]); hemodynamics (resting and post-exercise LVOT gradients); exercise capacity (pVO 2 ); biomarkers (NT-proBNP and hs-cTnI). NNT comparing mavacamten versus placebo was calculated as the reciprocal of the difference in response rates between the two groups at week 30 rounded up to an integer. Results (Table): The NNT to achieve the primary endpoint was 6. The NNTs were 3 for an improvement of ≥1 NYHA class and 4 for an improvement to NYHA class I. For PROs, the NNTs were 5 for an increase of ≥10 points in KCCQ CSS and 4 for a reduction of ≥2.5 points in HCMSQ SoB, which are considered clinically important changes. For hemodynamics, the NNTs were 2–3. For increases in pVO 2 ≥1.5 mL/kg/min and ≥3.0 mL/kg/min, the NNTs were 6 and 9, respectively. For biomarkers, the NNTs were 3 for any reduction in NT-proBNP and 5 for any reduction in hs-cTnI. Conclusions: The NNTs comparing mavacamten with placebo were consistently low across several clinical and PRO measures. This suggests that mavacamten may be an effective therapy for the treatment of symptomatic oHCM.