Mavacamten Shows Real-World Benefit for Obstructive Hypertrophic Cardiomyopathy Patients in Canada

A first-of-its-kind Canadian study reports that mavacamten, a selective cardiac myosin inhibitor, improved symptoms and reduced left ventricular outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy treated in routine clinical practice. The MAVEN study, published in Cardiology and Therapy, followed 115 patients across five Canadian cardiology centers and found that nearly three-quarters improved by at least one New York Heart Association functional class, while the obstruction-driving pressure gradients across the outflow tract fell substantially. Because the analysis was retrospective and descriptive, the authors emphasize that the findings should be interpreted cautiously and do not establish causation in the way a randomized trial would.

Hypertrophic cardiomyopathy affects roughly one in 500 people worldwide and is characterized by thickening of the left ventricular muscle in the absence of another cardiac, systemic, or metabolic disease. In nearly 70 percent of patients, the condition produces dynamic obstruction of the left ventricular outflow tract, the channel through which blood exits the heart. Roughly one-third of these patients show the obstruction at rest, while another third require provocation, such as the Valsalva maneuver, to reveal it. This obstruction is linked to breathlessness, reduced exercise capacity, and other symptoms, and patients with symptomatic obstructive disease face elevated risks of atrial fibrillation, heart failure, and malignant ventricular arrhythmias.

Conventional drug therapy for the condition, including beta blockers, calcium channel blockers, and disopyramide, primarily provides symptomatic relief and does not address the underlying molecular mechanisms, and it is often insufficient. For patients who do not respond to medications, septal reduction therapies such as surgical myectomy or alcohol septal ablation are options, but these procedures are invasive and, in Canada, access is limited to specialized centers. Mavacamten works differently: it selectively and reversibly inhibits cardiac myosin, targeting the hypercontractility at the root of the disease and normalizing the proportion of myosin heads available to bind with actin. The randomized controlled trials EXPLORER-HCM and VALOR-HCM demonstrated its efficacy in lowering outflow tract gradients and improving functional class, and Health Canada approved the drug in November 2022 for symptomatic obstructive disease in patients with NYHA class II or III symptoms.

Despite this regulatory approval, all prior efficacy and real-world studies had been conducted outside Canada. The MAVEN investigators therefore designed an observational, multi-center, retrospective physician survey of patient charts to capture how the drug performs within the Canadian healthcare system and its Patient Support Program, which was established to help patients and clinicians navigate treatment access. Unlike the United States, Canadian use does not require enrollment in a Risk Evaluation and Mitigation Strategy program, and unlike Europe, CYP2C19 genotyping is not required, although the recommended dosing and administration schedule remain consistent across jurisdictions.

The cohort comprised adults with symptomatic obstructive hypertrophic cardiomyopathy who initiated mavacamten through the Patient Support Program between January 2023 and November 2024 at five centers in Alberta, Ontario, and British Columbia. Patients were screened consecutively beginning with the earliest eligible index date to minimize selection bias, though the sample remained a convenience sample from high-volume centers. Baseline characteristics mirrored earlier trial and real-world populations: median age was 63.0 years, 66.1 percent were aged 60 or older, and the cohort was nearly evenly split by sex, with 51.3 percent male and 48.7 percent female. At treatment initiation, 57.4 percent of patients were in NYHA class II and 42.6 percent in class III. Median baseline resting and Valsalva outflow tract gradients were 44.0 and 78.0 mmHg, respectively, and median left ventricular ejection fraction was 65.0 percent.

Nearly all patients, 98.3 percent, started mavacamten at 5 mg daily, consistent with the Canadian product monograph, and about three-quarters remained on 5 mg at week 12. Effectiveness was assessed by comparing each patient’s most recent available clinical assessment with baseline values. After a median follow-up of 38.7 weeks, 72.7 percent of patients had improved by at least one NYHA functional class, and 46.1 percent reached NYHA class I. Median reductions were 25.5 mmHg for the resting gradient and 51.0 mmHg for the Valsalva gradient, with interquartile ranges of 61 to 8 and 83 to 24 mmHg respectively. At the data cut-off, 89.6 percent of patients achieved a resting gradient of 30 mmHg or less and 67.0 percent achieved a Valsalva gradient at or below that obstruction threshold. During treatment, the proportion of patients also taking background therapies fell from 80.9 percent to 70.4 percent, while mavacamten monotherapy rose from 19.1 percent to 29.5 percent, though the reasons for these treatment changes were not systematically captured.

On safety, the median treatment duration was 53.3 weeks, corresponding to 116.2 patient-years of exposure. A mild reduction in ejection fraction was observed, with a median change of minus 3.0 percent. Seven patients, 6.1 percent, experienced an ejection fraction below 50 percent, the threshold for left ventricular systolic dysfunction; four of these fell into the 40 to 50 percent range and three into the 30 to 39 percent range. No patient experienced an ejection fraction below 30 percent, the level that mandates permanent discontinuation in the pivotal trials. Among the seven affected patients, four subsequently recovered to 50 percent or above, two permanently discontinued treatment, and one restarted at a reduced dose. Overall, mavacamten was permanently discontinued in 8.7 percent of patients, including 2.6 percent who stopped because of treatment-emergent adverse events, a rate the authors describe as consistent with or lower than that seen in trials and other real-world settings.

Two exploratory post-hoc subgroup analyses were conducted to generate hypotheses for future management strategies. In the first, patients receiving mavacamten monotherapy throughout the observation period showed symptom and gradient improvements comparable to those on combination therapy, with 72.2 percent improving by at least one functional class and no monotherapy patients discontinuing due to adverse events, though the monotherapy group was older on average. The second analysis examined patients whose Valsalva gradient fell below 20 mmHg within the first 12 weeks, a threshold at which the Canadian product monograph recommends dose reduction. Both the dose-change and no-dose-change subgroups showed symptom improvements and gradient reductions, but improvements in functional class were not uniformly aligned with gradient reductions, suggesting that symptoms and hemodynamic measures may not always move in parallel. Given the small sample sizes, the authors stress these findings are descriptive and not predictive of individual patient response.

The study’s limitations are considerable and the authors lay them out plainly. The convenience sample from five high-volume centers may introduce selection bias and limits generalizability to the broader Canadian population. Data came from physician-completed chart surveys restricted to routinely available variables, so laboratory biomarkers, exercise testing measures such as the six-minute walk distance and cardiopulmonary exercise testing, and systematic adverse event capture beyond the protocol-defined ejection fraction outcomes were not available. Echocardiography followed each center’s routine practice without standardized acquisition protocols or core laboratory adjudication, introducing potential inter-site variability, and follow-up durations were heterogeneous, ranging from 5 to 95 weeks. All analyses were descriptive, without formal hypothesis testing or adjustment for confounding, so causal inferences cannot be made. Exercise stress echocardiography was not routinely performed, precluding assessment of residual exercise gradients as a cause of persisting symptoms. The authors call for prospective studies with standardized clinical and imaging assessments to better characterize the long-term effectiveness and safety of mavacamten, and for further work to clarify treatment monitoring and dose optimization in Canadian practice.

Subject of Research: Real-world effectiveness and safety of mavacamten in Canadian patients with obstructive hypertrophic cardiomyopathy

Article Title: Real-World Effectiveness of Mavacamten in Canada: Insights from the MAVEN Study

Article References: Ward, M. R., Crean, A. M., Desplantie, O., Tyrrell, B. D., Corriveau, S., Brellier, F., & Ong, K. C. (2026). Real-World Effectiveness of Mavacamten in Canada: Insights from the MAVEN Study. Cardiology and Therapy. https://doi.org/10.1007/s40119-026-00483-3

Image Credits: AI Generated

DOI: 10.1007/s40119-026-00483-3

Keywords: mavacamten, hypertrophic cardiomyopathy, obstructive HCM, LVOT gradient, NYHA functional class, left ventricular ejection fraction, real-world evidence, Canada, cardiac myosin inhibitor, retrospective chart review, Patient Support Program, Real-World