What is the role of beta blockers in treating resistant hypertension?

Beta-Blocker Use in Resistant Hypertension

Beta-blockers are recommended as a fourth-line agent in resistant hypertension, but only after spironolactone (or other mineralocorticoid receptor antagonists) has been tried first, and specifically when beta-blockers are not already indicated for compelling cardiac conditions. 1

Defining Resistant Hypertension

Resistant hypertension is diagnosed when blood pressure remains >140/90 mmHg despite treatment with three or more antihypertensive medications at optimal doses, including a diuretic, after excluding pseudoresistance (poor measurement technique, white coat effect, nonadherence) and secondary causes. 1

Treatment Algorithm for Resistant Hypertension

First Steps: Optimize Triple Therapy

• Ensure maximally tolerated doses of an ACE inhibitor or ARB, calcium channel blocker, and thiazide/thiazide-like diuretic are being used. 1
• Reinforce lifestyle measures, especially sodium restriction. 1
• Verify medication adherence before escalating therapy. 1

Fourth-Line Agent: Spironolactone First

• Add low-dose spironolactone (25-50 mg daily) as the preferred fourth-line agent if serum potassium is <4.5 mmol/L and eGFR is >45 mL/min/1.73m². 1
• Spironolactone has demonstrated superior blood pressure reduction compared to beta-blockers in resistant hypertension. 1

When to Use Beta-Blockers in Resistant Hypertension

Beta-blockers should be considered only if:

• Spironolactone is not tolerated or contraindicated (hyperkalemia, renal dysfunction). 1
• Eplerenone or amiloride have also failed or are not tolerated. 1
• The patient does not already have a compelling cardiac indication for beta-blockers (if they do, beta-blockers should already be part of the regimen). 1, 2

Selecting the Right Beta-Blocker

When a beta-blocker is chosen for resistant hypertension:

• Bisoprolol is specifically mentioned in the 2024 ESC Guidelines as an option for resistant hypertension. 1
• Vasodilating beta-blockers (carvedilol, nebivolol, labetalol) are preferred over traditional beta-blockers as they may provide better blood pressure reduction through combined mechanisms. 1, 2
• Avoid atenolol - it is less effective than placebo in reducing cardiovascular events and provides inferior stroke protection. 2, 3
• Cardioselective agents (metoprolol, bisoprolol) are preferred if the patient has reactive airway disease. 2

Important Clinical Considerations

Why Beta-Blockers Are Not First Choice

• Beta-blockers are less effective than spironolactone for blood pressure reduction in resistant hypertension. 1
• Traditional beta-blockers (especially atenolol) show inferior cardiovascular outcomes compared to other antihypertensive classes in uncomplicated hypertension. 3, 4
• They are most effective in neurogenic/sympathetically-driven hypertension, which may not be the primary mechanism in all resistant hypertension cases. 5

Specific Patient Populations Where Beta-Blockers May Be Preferred Earlier

Beta-blockers should already be part of the treatment regimen (not reserved as fourth-line) in resistant hypertension patients with:

• Stable ischemic heart disease or angina pectoris. 2
• Previous myocardial infarction. 2
• Heart failure with reduced ejection fraction. 2
• Tachyarrhythmias requiring rate control. 2
• Elevated resting heart rate (>80 bpm), which independently increases cardiovascular risk. 1

Dosing and Monitoring

• Bisoprolol: 2.5-10 mg once daily. 1, 2
• Carvedilol: 12.5-50 mg twice daily (or 20-80 mg once daily for phosphate form). 1, 2
• Metoprolol succinate: 50-200 mg once daily. 1, 2
• Never abruptly discontinue beta-blockers - taper to avoid rebound hypertension or exacerbation of angina. 2
• Monitor heart rate carefully, especially in elderly patients, to avoid excessive bradycardia. 2

Common Pitfalls to Avoid

• Do not use beta-blockers as first-line therapy in resistant hypertension - spironolactone is superior. 1
• Do not combine beta-blockers with non-dihydropyridine calcium channel blockers (verapamil, diltiazem) due to increased risk of bradycardia and heart block. 1
• Do not assume all beta-blockers are equivalent - atenolol should be avoided, and vasodilating beta-blockers offer advantages. 2, 3
• Do not overlook compelling cardiac indications - if present, beta-blockers should be incorporated earlier in the treatment regimen, not reserved as fourth-line. 1, 2

Referral Considerations

Patients with resistant hypertension should be referred to specialist centers with expertise in managing this condition, particularly before considering interventional therapies like renal denervation. 1