What is the role of beta (beta blockers) blockers, such as metoprolol (metoprolol succinate) or atenolol, in the treatment of hypertension, particularly in patients with comorbidities like heart failure or coronary artery disease?

Beta-Blockers for Hypertension: An Evidence-Based Approach

Beta-blockers should not be used as first-line therapy for uncomplicated hypertension, but are strongly indicated when hypertension coexists with specific cardiovascular comorbidities including heart failure with reduced ejection fraction, post-myocardial infarction, coronary artery disease with angina, or arrhythmias requiring rate control. 1

Preferred Beta-Blockers: Agent Selection Matters

When beta-blocker therapy is indicated, agent selection is critical as not all beta-blockers are equivalent in cardiovascular outcomes. 2

First-Choice Agents

• Carvedilol (12.5-50 mg twice daily) is the optimal choice due to combined alpha- and beta-blocking properties, favorable hemodynamic profile, and beneficial effects on insulin resistance with antioxidant properties 2, 3, 4
• Metoprolol succinate (50-200 mg once daily) offers cardioselective beta-1 blockade with convenient once-daily dosing and is particularly effective in heart failure with reduced ejection fraction 2, 3
• Bisoprolol (2.5-10 mg once daily) provides cardioselective beta-1 blockade with once-daily dosing and FDA indication for hypertension 2, 3

Agents to Avoid

Atenolol should never be used as it is less effective than placebo in reducing cardiovascular events and demonstrates inferior outcomes in major trials, with a 26% higher risk of stroke compared to other antihypertensive drugs. 2, 3, 5 The FDA label confirms atenolol's limitations, noting it may increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure, particularly in heart failure patients. 6

Avoid beta-blockers with intrinsic sympathomimetic activity (acebutolol, penbutolol, pindolol), especially in patients with ischemic heart disease or heart failure. 2

Compelling Indications: When Beta-Blockers Are First-Line

Beta-blockers become first-line therapy when hypertension coexists with the following conditions:

Cardiac Indications

• Post-myocardial infarction (especially with hypertension, tachycardia, angina, arrhythmias, heart failure, or incomplete revascularization) 1
• Stable ischemic heart disease with symptomatic angina 1, 7
• Heart failure with reduced ejection fraction 1, 2
• Heart failure with mid-range ejection fraction (40-49%) where beta-blockers improve left ventricular ejection fraction and reduce all-cause and cardiovascular mortality 1
• Acute coronary syndrome with persistent ischemia, angina, or arrhythmias (first-choice treatment regardless of hypertension status) 1
• Uncontrolled rapid atrial fibrillation (combined with diltiazem or verapamil to avoid toxic amiodarone) 1
• Long QT syndrome to prevent torsades de pointes and sudden cardiac death 1
• Hypertrophic obstructive cardiomyopathy or subaortic stenosis 1
• Post-cardiac surgery (CABG, valve replacement, or other major cardiac procedures) 1
• Post-ICD or pacemaker implantation for tachycardia control 1

Heart Rate Control

Elevated resting heart rate in hypertensive patients represents an independent cardiovascular risk factor that increases cardiac work, myocardial oxygen demand, arterial wall stress, and facilitates coronary plaque disruption. 1 Beta-blockers are particularly appropriate in young or middle-aged hypertensive patients with hyperkinetic circulation and elevated heart rate. 1

Special Populations and Safety Considerations

COPD and Respiratory Disease

Cardioselective beta-blockers (bisoprolol, metoprolol) are not only safe but beneficial in patients with COPD and hypertension, reducing all-cause and in-hospital mortality while potentially reducing COPD exacerbations. 3, 8 Target heart rate of 60-70 beats/min when using these agents. 3, 8

Critical distinction: True pulmonary asthma remains a stronger contraindication, as even cardioselective agents may worsen asthma. 8 Non-selective beta-blockers should be absolutely avoided in bronchospastic disease. 6

Diabetes

Vasodilating beta-blockers (carvedilol, nebivolol) are preferred over traditional agents in diabetic patients due to more favorable metabolic profiles and superior glycemic control effects. 3, 4 Traditional beta-blockers may mask hypoglycemic tachycardia, though other manifestations like dizziness and sweating remain detectable. 6

Pregnancy

Metoprolol and labetalol are considered safe during pregnancy. 3 However, atenolol administration starting in the second trimester has been associated with infants small for gestational age, and neonates may be at risk for hypoglycemia and bradycardia. 6

Peripheral Artery Disease

Beta-blockers are now shown to be protective and safe in peripheral artery disease, contrary to traditional restrictions. 1

Age-Related Considerations

In patients younger than 60 years, beta-blockers reduce cardiovascular risk including death, stroke, and MI. 9 However, in patients 60 years or older, beta-blockers are not associated with significantly lower rates of MI, heart failure, or death, and demonstrate higher stroke rates compared to other first-line therapies. 9 Therefore, use beta-blockers as first-line only in hypertensive patients under 60 years without compelling indications, or in those 60 and older only when beta-blocker-requiring cardiac diseases coexist. 9

Combination Therapy Strategy

When additional blood pressure control is needed beyond beta-blocker monotherapy:

• Dihydropyridine calcium channel blockers are effective for persistent hypertension and angina 2
• ACE inhibitors or ARBs provide additional control, especially with compelling indications 2
• Thiazide diuretics enhance blood pressure reduction 2

Important caveat: Avoid combining beta-blockers with non-dihydropyridine calcium channel blockers (verapamil, diltiazem) as this can cause bradycardia, heart block, and increased left ventricular end diastolic pressure, particularly in patients with pre-existing conduction abnormalities or left ventricular dysfunction. 6

Critical Warnings and Contraindications

Abrupt Discontinuation

Never abruptly discontinue beta-blockers in patients with coronary artery disease. Severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias have been reported following abrupt cessation. 6 When discontinuation is planned, carefully observe patients, advise limiting physical activity, and consider tapering. 6

Heart Failure

In acute myocardial infarction, cardiac failure not promptly controlled by 80 mg intravenous furosemide or equivalent is a contraindication to beta-blocker treatment. 6 In patients without heart failure history, monitor for signs of impending cardiac failure and withdraw beta-blocker if failure continues despite adequate treatment. 6

Untreated Pheochromocytoma

Beta-blockers should never be given to patients with untreated pheochromocytoma. 6

Monitoring Parameters

• Bronchospasm risk (especially with non-cardioselective agents) 2
• Blood pressure response with dosage adjustment accordingly 2
• Heart rate targeting 60-70 beats/min in appropriate populations 3, 8
• Signs of cardiac decompensation in at-risk patients 6

Pathophysiologic Rationale

The sympathetic nervous system is activated throughout hypertension progression and in related conditions including heart failure, ischemic heart disease, obesity, and obstructive sleep apnea, making beta-blockade mechanistically appropriate. 1 Beta-blockers substantially reduce stroke risk in placebo-controlled trials and lower blood pressure as effectively as other major antihypertensive classes. 1