Is it safe to use Camzyos (mavacamten) and losartan together in patients with Hypertrophic Cardiomyopathy (HCM)?

Camzyos (Mavacamten) and Losartan Combination in HCM

Losartan can be safely used with Camzyos (mavacamten) in patients with hypertrophic cardiomyopathy when indicated for comorbid hypertension, as losartan does not adversely affect mavacamten therapy and was used without clinically adverse consequences in HCM trials. 1

Evidence Supporting Concurrent Use

Losartan Safety Profile in HCM

• A 12-month placebo-controlled trial of 124 HCM patients (112 with LVOT gradient <30 mm Hg) demonstrated that losartan treatment was without clinically adverse consequences and could be used for other indications when needed. 1
• While losartan showed no benefit for reducing LV mass, fibrosis, or improving functional class in HCM specifically, it did not worsen outcomes or interfere with HCM management. 1

Guideline Recommendations for ARBs in HCM

• The 2011 ACC/AHA guidelines classify angiotensin receptor blockers (including losartan) as Class III: Harm only when used specifically to treat HCM symptoms (angina or dyspnea) in patients with resting or provocable LVOT obstruction. 1
• However, the 2024 ACC/AHA guidelines explicitly state that comorbidities contributing to cardiovascular disease (including hypertension) should be treated in compliance with existing guidelines. 1

Mavacamten Clinical Trial Experience

• In the EXPLORER-HCM trial, 47.4% of patients had concurrent hypertension, and mavacamten demonstrated similar clinical benefits regardless of hypertension status. 2
• Most patients (92.3%) in the PIONEER-OLE long-term safety study received β-blockers concomitantly with mavacamten without safety concerns. 3
• The VALOR-HCM trial showed sustained efficacy through 128 weeks with 88% of patients transitioning to commercial mavacamten, indicating real-world compatibility with standard comorbidity management. 4

Clinical Algorithm for Combined Use

When to Use Losartan with Mavacamten

1. Primary indication: Hypertension requiring treatment - Losartan is appropriate when blood pressure control is needed beyond HCM-specific therapy. 1
2. Avoid using losartan specifically to treat HCM symptoms (dyspnea, angina) in patients with LVOT obstruction, as it provides no benefit for these indications. 1
3. Monitor for hypotension - Both mavacamten (through reduced contractility) and losartan (through vasodilation) can lower blood pressure; careful monitoring is essential. 1

Monitoring Parameters

• Blood pressure monitoring - Check for symptomatic hypotension or orthostatic symptoms, particularly in patients with autonomic dysfunction. 1
• LVEF surveillance - Continue standard mavacamten monitoring with echocardiography every 12 weeks during dose titration, then every 6 months, as losartan does not alter this requirement. 3, 5
• Symptom assessment - Evaluate for lightheadedness or dizziness that may warrant losartan dose reduction. 1

Important Caveats

Obstructive vs. Nonobstructive HCM

• In patients with significant resting or provocable LVOT obstruction (gradient ≥30 mm Hg), use losartan cautiously and only for clear hypertension indications, not for HCM symptom management. 1
• In nonobstructive HCM, losartan carries less theoretical risk but still provides no HCM-specific benefit. 1

End-Stage HCM Exception

• In end-stage HCM with systolic dysfunction (LVEF <50%), mavacamten should be discontinued due to profound negative inotropic effects, but losartan becomes appropriate as part of heart failure with reduced ejection fraction guideline-directed medical therapy. 1

Drug Interaction Considerations

• No direct pharmacokinetic interaction exists between mavacamten and losartan. 3, 6
• Avoid combining losartan with other vasodilators (dihydropyridine calcium channel blockers, nitrates) in obstructive HCM, as cumulative vasodilation may worsen LVOT obstruction. 1

Bottom Line for Clinical Practice

Prescribe losartan with mavacamten when hypertension requires treatment, ensuring blood pressure targets are met without causing symptomatic hypotension. 1, 2 Do not use losartan as HCM-specific therapy for symptom relief in obstructive disease. 1 The combination is safe based on trial data showing no adverse consequences, but requires standard monitoring for both medications. 1, 3