What is the role of metoprolol (metoprolol succinate) in the management of hypertensive cardiomyopathy?

Metoprolol Succinate for Hypertensive Cardiomyopathy

Metoprolol succinate is highly recommended as a first-line therapy for hypertensive cardiomyopathy due to its proven efficacy in reducing mortality, improving cardiac function, and providing consistent 24-hour blood pressure control. 1

Mechanism of Action and Benefits

• Metoprolol succinate is a beta-1 selective adrenergic receptor blocker that provides relatively constant plasma concentrations and beta-1 blockade with once-daily dosing 2, 3
• It reduces cardiac workload by decreasing heart rate, blood pressure, and myocardial contractility, which helps alleviate the burden on the hypertrophied heart 2, 4
• The controlled-release/extended-release formulation maintains consistent beta-blockade over 24 hours, reducing fluctuations in plasma concentrations compared to immediate-release formulations 5

Evidence Supporting Use in Hypertensive Cardiomyopathy

• Metoprolol succinate has demonstrated significant reduction in left ventricular outflow tract (LVOT) gradients in hypertrophic cardiomyopathy patients: 25 mm Hg vs 72 mm Hg at rest (p=0.007) and 28 mm Hg vs 62 mm Hg at peak exercise (p<0.001) 4
• In patients with dilated cardiomyopathy and hypertension, metoprolol significantly improved left ventricular end-diastolic dimension (LVEDD), left atrial end-diastolic dimension (LAEDD), and left ventricular ejection fraction (LVEF) 6
• The MERIT-HF trial showed metoprolol CR/XL reduced all-cause mortality by 34%, sudden death by 41%, and death due to progressive heart failure in patients with heart failure 7, 5

Dosing Considerations

• Treatment should be initiated at a low dose (12.5-25 mg once daily) and gradually titrated upward at 2-week intervals to the target dose (200 mg once daily) or maximum tolerated dose 1, 7
• Patients with hypertensive cardiomyopathy may tolerate higher doses of metoprolol (studies show average tolerable doses of 189.6 ± 14.8 mg/day in hypertensive cardiomyopathy patients) 6
• The controlled-release formulation (metoprolol succinate) is preferred over immediate-release (metoprolol tartrate) due to more consistent beta-blockade and once-daily dosing convenience 1, 5

Place in Treatment Algorithm

1. First-line therapy: Metoprolol succinate is recommended as a first-line agent for hypertensive cardiomyopathy 1
2. For patients with hypertension and heart failure with reduced ejection fraction (HFrEF), metoprolol succinate is one of the three beta-blockers (along with carvedilol and bisoprolol) proven to reduce mortality 1
3. For patients with stable ischemic heart disease and hypertension, metoprolol succinate is a guideline-directed medical therapy (GDMT) beta-blocker 1

Combination Therapy

• In patients with persistent symptoms despite beta-blocker therapy, adding an ACE inhibitor or ARB is recommended 1
• For patients with angina and uncontrolled hypertension, dihydropyridine calcium channel blockers can be added to metoprolol 1
• In African American patients with advanced heart failure, consider adding hydralazine/isosorbide dinitrate to the regimen 1
• For severe heart failure, aldosterone receptor antagonists (spironolactone or eplerenone) can be added to the treatment regimen 1

Special Considerations and Monitoring

• Monitor for bradycardia, hypotension, and worsening heart failure symptoms, especially during initiation and dose titration 2
• Metoprolol is primarily metabolized by CYP2D6; poor metabolizers (8% of Caucasians, 2% of other populations) may have higher plasma concentrations and decreased cardioselectivity 2
• Elderly patients may show slightly higher plasma concentrations but generally don't require dose adjustment 2
• No dose adjustment is typically needed in patients with renal impairment, but dose should be adjusted in hepatic impairment as elimination half-life can be prolonged 2

Target Blood Pressure

• The target blood pressure for patients with hypertensive cardiomyopathy is <130/80 mmHg 1
• In some patients with heart failure, lower systolic blood pressure (110-130 mmHg) may be desirable 1
• Caution is advised when lowering diastolic blood pressure below 60 mmHg in patients over 60 years or with diabetes mellitus due to risk of myocardial ischemia 1

Metoprolol succinate's proven mortality benefit, consistent 24-hour blood pressure control, and improvement in cardiac function parameters make it an excellent choice for managing hypertensive cardiomyopathy.