Why do beta blockers help in the chronic phase of heart failure?

From the Guidelines

Beta blockers help in the chronic phase of heart failure by blocking the harmful effects of excessive sympathetic nervous system activation, thereby reducing morbidity and mortality, and improving quality of life. In heart failure, the body compensates by increasing adrenaline and noradrenaline, which initially helps but eventually damages the heart. Beta blockers such as carvedilol, metoprolol succinate, and bisoprolol reduce this damage by blocking beta-adrenergic receptors, allowing the heart to remodel positively over time. These medications are typically started at low doses (e.g., carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg daily, or bisoprolol 1.25 mg daily) and gradually increased every 2-4 weeks to target doses as tolerated.

Key Benefits of Beta Blockers

• Improve survival by reducing the risk of death and hospitalization 1
• Enhance quality of life by decreasing heart rate, reducing oxygen demand, improving cardiac efficiency, and preventing arrhythmias
• Help restore beta-receptor function that becomes downregulated in heart failure

Important Considerations

• Patients should be clinically stable before starting these medications, as they can initially worsen symptoms before providing benefits that typically emerge after weeks to months of consistent use 1
• The use of beta blockers is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality 1
• Beta blockers have been shown to be effective in reducing the risk of death in patients with chronic HFrEF, with a consistent 30% reduction in mortality and a 40% reduction in hospitalizations 1

From the Research

Benefits of Beta Blockers in Chronic Phase of Heart Failure

• Beta blockers have become an established treatment concept in chronic heart failure, providing a rationale for their use in patients with chronic heart failure due to the increased activation of the adrenergic system 2.
• Long-term treatment with beta blockers, in addition to ACE-inhibitors and diuretics, results in normalization of left ventricular shape, improvement of left ventricular function, and reduction of hospitalization rate for heart failure 2.
• Beta blockers have been shown to reduce total mortality and the incidence of sudden cardiac death in heart failure patients, with studies such as CIBIS II, MERIT-HF, and COPERNICUS demonstrating significant reductions 2.

Mechanisms of Action

• The protective effects of beta blockers in heart failure comprise a decrease in heart rate, a decrease of energy consumption, antifibrillatory effects, protection against adrenergic overactivation, and inhibition of myocardial cell necrosis 2.
• Beta blockers can also induce an up-regulation of beta-receptors, leading to an improvement of contractility during long-term treatment 2.

Selection and Initiation of Beta Blocker Therapy

• Bisoprolol, carvedilol, and metoprolol succinate have been clearly proven to reduce mortality and hospitalization in patients with Class II to IV heart failure, with limited evidence also supporting short-acting metoprolol tartrate and nebivolol 3.
• Initiating dose should be very low and increased gradually over weeks, with treatment benefit appearing proportional to magnitude of heart rate reduction 3.
• Even in decompensated heart failure or those with coexisting bronchospasm, beta blockers are not contraindicated, although the dose may have to be reduced or withheld temporarily 3.

Comparison of Different Beta Blockers

• Carvedilol and extended-release metoprolol succinate are two beta blockers currently approved in the United States for the treatment of patients with heart failure, with similar risk reductions in overall and cause-specific mortality 4.
• A comparative trial found no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate after multivariable adjustment or multilevel propensity score matching 5.