Abstract
PurposeThe aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States. MethodsA Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without β-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age- and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those for class I in conjunction with the relative mortality risks derived using patients with obstructive HCM from a large real-world registry. Health state utilities for each treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated over a lifetime for each treatment arm, discounted at 3% annually, and compared between the 2 arms. Sensitivity analyses were conducted to evaluate the robustness of the model findings. FindingsOver a lifetime, treatment with mavacamten with or without BB or CCB monotherapy was associated with 3.67 incremental LYs compared with placebo with or without BB or CCB monotherapy (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in the mavacamten group were projected to spend 6.17 additional LYs in NYHA functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and III/IV, respectively. With utilities incorporated, mavacamten with or without BB or CCB monotherapy was associated with 4.17 additional QALYs compared with placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 2.48 to 6.19 QALYs across the scenarios. ImplicationsThis model projected substantial net health benefits associated with mavacamten for symptomatic obstructive HCM owing to improved patient survival and quality of life. The projected QALY gain underscored the likely long-term clinical value of mavacamten in symptomatic obstructive HCM.
Highlights
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder that is caused by excessive cardiac myosin–actin cross-bridging,[1,2] with core pathophysiologic features that include left ventricular hypertrophy, hypercontractility, diastolic dysfunction, and poor left ventricular compliance.[3,4] HCM can be hereditary, with up to 60% of cases estimated to be associated with autosomal dominant genetic mutations in cardiac sarcomere proteins.[3]
We developed a Markov model to project the potential lifetime net health benefits of mavacamten with or without BB or calcium channel blocker (CCB) monotherapy compared with placebo with or without BB or CCB monotherapy among adult patients with symptomatic obstructive HCM
A Markov model was developed in Microsoft Office 365 Excel (Microsoft Corp, Redmond, Washington) to assess the net health benefits as measured by lifeyears (LYs) and quality-adjusted life-years (QALYs) associated with mavacamten with or without BB or CCB monotherapy compared with placebo with or without BB or CCB monotherapy for the treatment of symptomatic obstructive HCM in the United States
Summary
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder that is caused by excessive cardiac myosin–actin cross-bridging,[1,2] with core pathophysiologic features that include left ventricular hypertrophy, hypercontractility, diastolic dysfunction, and poor left ventricular compliance.[3,4] HCM can be hereditary, with up to 60% of cases estimated to be associated with autosomal dominant genetic mutations in cardiac sarcomere proteins.[3]. Current pharmacologic therapies for obstructive HCM include β-blockers (BBs), calcium channel blockers (CCBs), and antiarrhythmic drugs[7]; these treatments are generally inadequate or poorly tolerated and are not disease specific.[8] invasive procedures that remove thickening of the septal wall (eg, septal reduction therapy [SRT]) may be considered, eligible patients must meet stringent clinical criteria.[4] Importantly, short-term and longterm complications associated with SRT, including death, may vary substantially, with irreversible poor outcomes, depending on the experience and skill of the centers that perform the procedures.[9,10,11] This variability raises concerns about equitable access to high-quality invasive procedures. There is a large, unmet treatment need for patients with symptomatic obstructive HCM; the disease poses a substantial burden for patients and health care systems
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