How Clinical Pharmacists Optimize Obstructive Hypertrophic Cardiomyopathy Care

The management of obstructive hypertrophic cardiomyopathy (oHCM) is witnessing a paradigm shift, transitioning from nonspecific symptom management to targeted precision medicine. At the forefront of this evolution are clinical pharmacists, who are increasingly taking the lead in navigating the complexities of cardiac myosin inhibitor (CMI) therapy.

In a recent Pharmacy Times Insights discussion titled “Obstructive HCM Insights: Best Practices for Clinical Pharmacists and Targeted CMI Therapy,” Andrew Willeford, PharmD, PhD, BCCP, an assistant professor at the University of California – San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences; and Laura Velazquez, PharmD, PhC, BCACP, a pharmacist clinician at Presbyterian Heart and Vascular, shared their perspectives on optimizing care for this patient population.

Distinguishing oHCM Within the Clinical Landscape

For health-system pharmacists, the first step in optimizing therapy is a clear understanding of the disease pathology. Accurately determining whether a patient has obstructive or nonobstructive disease ensures that the proper therapies are administered and that a patient’s treatment plan is adjusted accordingly.

“I think [that] hypertrophic cardiomyopathy or HCM is really more of an umbrella term,” Willeford explained. “And that umbrella term includes oHCM and nonobstructive HCM.” This distinction is critical because oHCM, characterized by dynamic outflow obstruction—typically due to hypertrophy in the basal septal area—is the form with the most robust evidence for targeted CMI therapies.¹

Unlike traditional treatments—such as β-blockers or calcium channel blockers—which only compensate for hemodynamic consequences, CMIs address the underlying disease pathophysiology. Velazquez utilizes a vivid analogy to explain this to her patients and the benefits they can expect following therapy, including being able to exercise and be more active without recurrent symptoms.¹

“I like to imagine the muscle proteins of the heart or myosin proteins as rowers in a boat, and the rowers in HCM are overactive,” Velazquez noted. She explained that this overactivity leads to stiffness and excessive energy use, because the rowers are “rowing too hard, too forcefully.” In the case of oHCM, the heart muscle can bulge out. “These cardiac myosin inhibitors or CMIs, they put these myosin proteins into more of a relaxed state so that some of the rowers are taking a break.”¹

Mavacamten: The Gold Standard in Targeted Therapy

Since its approval, mavacamten (Camzyos; Bristol Myers Squibb) has established itself as a transformative first-line targeted therapy. Beyond alleviating symptoms like shortness of breath and chest pain, mavacamten offers significant structural benefits, including decreased wall thickness and reduced NT-proBNP levels.^1,2

One of the most compelling advantages of mavacamten is its ability to help patients avoid invasive procedures. “Patients taking mavacamten have reduced rates of being referred for septal reduction therapy,” Velazquez highlighted, noting the importance of avoiding the “knife” of a myectomy. Willeford agreed, adding that a medication providing such high-quality results is a “huge win” for patients, especially since specialized centers for invasive procedures are limited.^1,2

Real-world evidence from the Risk Evaluation and Mitigation Strategy (REMS) program has instilled great confidence in the pharmacy community, offering impressive safety and efficacy data. Willeford pointed out that 22-month REMS data showed the rate of ejection fraction (EF) decline to less than 50% was only 4%, which is lower than the 6% observed in the pivotal phase 3 EXPLORER-HCM trial (NCT03470545). Updated 34-month data remains strong at approximately 7%, highlighting the durability of mavacamten in preventing dangerous declines in EF.^2,3

“Overall...it appears like the safety is a little bit better in real-world practice,” Willeford remarked, attributing this partly to the conservative 12-week dosing buffer used in practice. “That helps instill confidence in patients to know that it’s a safe medication. It looks better, potentially, than what was even studied in the clinical trials.”²

The Role of Aficamten as a Secondary Therapy

As of December 2025, the CMI class has expanded with the approval of aficamten (Myqorzo; Cytokinetics). While mavacamten remains the cornerstone of therapy with extensive long-term safety data, aficamten offers a secondary option with distinct pharmacological properties.¹

“Aficamten does have a shorter half-life,” Velazquez noted, adding that it lacks clinically significant cytochrome P450 enzyme interactions and features a shallower dose-response relationship. These factors may allow for more rapid titration and a wider therapeutic window; however, she cautioned that the long-term data for aficamten are still ongoing, compared with the nearly 4 years of established evidence for mavacamten. Velazquez suggested that aficamten might be prioritized in cases where rapid titration is necessary or when significant drug-drug interactions in certain patients make mavacamten use difficult.¹

The Pharmacist-Led Management Model

Health-system pharmacists are uniquely positioned to manage the specialized workflows required for CMIs, like their role in guideline-directed medical therapy for heart failure. “It is extremely, extremely useful having a pharmacist in clinic to take care of this entire workflow,” Willeford stated, noting that pharmacists can manage echo ordering, follow-up, and dose adjustments under collaborative practice agreements. In New Mexico, Velazquez even utilizes a “pharmacist clinician license” that provides prescriptive authority to manage CMI patients autonomously.³

To ensure patient safety, pharmacists must be vigilant regarding drug-drug interactions. Mavacamten is extensively metabolized by CYP2C19, necessitating careful screening. Velazquez recommends screening at multiple touchpoints, as common OTC acid reducers for gastroesophageal reflux disease (GERD) can be “notorious offending medications.” She noted that pharmacists can “preemptively discuss with [patients] if they have GERD and which therapies they can use in the instance of future symptoms. It’s a way to get ahead of it.”³

Willeford encourages pharmacists to be a reassuring resource. “I don’t want you to worry about figuring out your drug interactions. All I want you to do is just call and tell me, and let me worry about figuring it out for you,” he explained to a hypothetical patient.³

Ultimately, implementing a successful CMI program requires creative use of health system resources. Willeford shared a “mind-blowing” best practice: using the reminder list function in Epic, an electronic health record software for health systems, hospitals, and academic centers, to track echo dates and status forms. “We’ve had...over 115 total patients come to us...and we’ve never had an issue with losing track of them because of that reminder list tool,” he said. He has also developed Excel-based calculators to help clinicians navigate the specific echo windows required by the REMS program.³

By driving the standard of care, clinical pharmacists are not only reducing physician burden but also ensuring that patients with oHCM receive the full benefit of these life-changing targeted therapies. As Velazquez aptly summarized, even if therapy must be temporarily held due to EF changes, the process is reversible, and the long-term outlook for these patients has never been brighter.³

“Use pharmacists as your resource to feel secure in what you’re taking, whether it’s mavacamten or anything else,” Willeford said.³

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REFERENCES

1. Willeford A, Velazquez L. Counseling patients with oHCM—using data to instill confidence. Pharmacy Times. February 17, 2026. Accessed April 6, 2026. https://www.pharmacytimes.com/view/counseling-patients-with-ohcm-using-data-to-instill-confidence

2. Willeford A, Velazquez L. Treatment options for oHCM—aligning guidance with real-world data to improve outcomes. Pharmacy Times. February 17, 2026. Accessed April 6, 2026. https://www.pharmacytimes.com/view/treatment-options-for-ohcm-aligning-guidance-with-real-world-data-to-improve-outcomes

3. Willeford A, Velazquez L. The role of clinical pharmacists—best practices and early execution. Pharmacy Times. February 23, 2026. Accessed April 6, 2026. https://www.pharmacytimes.com/view/the-role-of-clinical-pharmacists-best-practices-and-early-execution