Abstract 10969: 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

Abstract

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.

Review of Mavacamten for Obstructive Hypertrophic Cardiomyopathy and Future Directions

“…The number needed to treat (NNT) was also quite promising with NNT of 2, 3 and 4 for reduction of LVOT gradient <50mmHg, improvement in NYHA > 1 class grade and improvement to NYHA class 1, respectively. 20 Regarding adverse events, safety and tolerability were similar in both groups. There were seven patients in the mavacamten group and three patients in the placebo group whose EF decreased to <50%.…”

“…The number needed to treat (NNT) was also quite promising with NNT of 2, 3 and 4 for reduction of LVOT gradient <50mmHg, improvement in NYHA > 1 class grade and improvement to NYHA class 1, respectively. 20 …”

Cardiac Myosin Inhibitors as a Novel Treatment Option for Obstructive Hypertrophic Cardiomyopathy: Addressing the Core of the Matter

“…Overall, mavacamten was effective, with a number needed to treat of 2, 3, and 4 at 30 weeks, respectively, for the endpoints of LVOT gradient reduction ≤50 mm Hg, improvement in NYHA by ≥1 class, and improvement to NYHA class I. 21 While such proportion of responders may be seen to compare unfavorably with published SRT results, it must be emphasized that patients enrolled in EXPLORER‐HCM were not immediate candidates for SRT (operative referral being an exclusion criterion), and that about two‐thirds were in NYHA class 2, while only the remaining third were in class 3. In addition, the results of a prospective double‐blind placebo‐controlled, randomized trial cannot be compared with those from retrospective SRT studies, in view of inherent limitations of the latter.…”