Beta-Blocker Usage in Patients With Heart Failure With Reduced Ejection Fraction During Acute Decompensated Heart Failure Hospitalizations

Presentation of Acute Decompensated Heart Failure

Patients presenting with acute decompensated heart failure require immediate medical evaluation and treatment. In-hospital mortality rates for acute decompensated heart failure hospitalizations range from 4.2% to 5.3%, increasing to 22% to 27% within 1 year of hospitalization.^12,13 However, most presentations of decompensated heart failure are not acute. Instead, patients typically present to the hospital following a gradual increase in cardiac filling pressures coupled with a precipitating event.⁹ The most common precipitating factors in descending order are pneumonia or respiratory processes, arrhythmias, medication noncompliance, renal failure, and uncontrolled hypertension.¹⁴

To aid in the management of acute decompensated heart failure, patients are assigned to 1 of 4 categories depending on whether they show signs of congestion (ie, wet vs dry) or hypoperfusion (ie, cold vs warm).¹⁵ A study of 7,865 patients in the European Heart Failure Long-Term Registry found that patients most often fell into the warm-wet classification (70%), followed by cold-wet (20%), warm-dry (10%), and cold-dry (0.4%).¹³ Of note, hypotension (systolic blood pressure <90 mm Hg) is not necessary to diagnose hypoperfusion; only 5% to 8% of patients with acute decompensated heart failure present with hypotension.¹⁵ Instead, clinicians rely on clinical signs such as cold extremities, oliguria, or altered mental status.

Management of Acute Decompensated Heart Failure

Management of patients with acute decompensated heart failure should focus on addressing reversible factors, optimizing volume status, and prescribing guideline-directed medical therapy.⁹ Optimization of volume status entails the use of loop diuretics to relieve congestion.¹⁶ In rare instances—such as a patient with low systolic blood pressure, hypoperfusion, and heart failure with reduced ejection fraction—inotropes may be required.¹⁷

As shown in Table 1, beta-blockers are a mainstay of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction. Accordingly, professional societies recommend continuing or initiating beta-blockers during a hospitalization for acute decompensated heart failure in most situations (Table 2).^4,9-11 We have created a guideline-based flowchart to help physicians determine when or whether to withdraw beta-blockers during a hospitalization for acute decompensated heart failure (Figure).

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Figure.

Guideline-based flowchart for using beta-blockers in patients with heart failure with reduced ejection fraction who present with acute decompensated heart failure.

The other components of guideline-directed medical therapy include renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors.⁹ Greene et al analyzed medications taken by patients with heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure (CHAMP-HF) registry and found that the guideline-directed medical therapy medications most often reduced in dosage were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and beta-blockers.¹⁸

Physicians may have concerns about continuing a medication with negative inotropic effects at a time of worsening hemodynamics.¹⁹ This instinct may make sense in theory but does not hold in practice for several reasons. First, the initial goal in the management of acute decompensated heart failure is to address reversible factors. Beta-blocker medications would be a suspected culprit of decompensation only if they were initiated or increased shortly before the hospitalization. If not, physicians should look elsewhere for reversible factors precipitating an acute decompensated heart failure hospitalization. Second, sudden cessation of beta-blocker treatment may cause further adverse outcomes by causing a rebound of the sympathetic nervous system.²⁰ Beta-blocker withdrawal has been shown to increase angina and the risk of coronary events.²¹

Despite the reasoning for the continuation of beta-blocker therapy during hospitalization for acute decompensated heart failure, many providers fail to administer them. In a 2018 analysis of the CHAMP-HF registry, just 67% of patients with heart failure with reduced ejection fraction were prescribed beta-blockers.²² An analysis of claims data from 2009 to 2012 found that 42% of patients with heart failure with reduced ejection fraction were not prescribed any heart failure–specific medications as of 30 days following hospitalization.²³ Although hypoperfusion is observed in only about 1 in 5 patients with acute decompensated heart failure,¹³ physicians often cited “medical reasons” as the impetus for reducing dosages of beta-blocker therapy.¹⁸

Withdrawal of Beta-Blocker Therapy During Hospitalization Is Harmful

The withdrawal of beta-blockers in patients with heart failure with reduced ejection fraction experiencing acute decompensated heart failure is harmful in the short and long term. In the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF), patients whose beta-blocker treatment was withdrawn had higher rates of mortality compared to patients who continued beta-blocker treatment.²⁴ A 2015 meta-analysis found beta-blocker discontinuation to be associated with an increased risk of both in-hospital mortality and short-term mortality (≤6 months of first hospitalization).¹⁹ Beta-blocker discontinuation also led to a higher risk of the combined outcome of rehospitalization or mortality.¹⁹

Maintenance of Beta-Blocker Therapy Is Beneficial

Studies support the claim that continuation of beta-blocker therapy throughout hospitalization leads to significant benefits. The OPTIMIZE-HF trial found reductions in 60-day mortality, 90-day mortality, and the combined outcome of rehospitalization or mortality in patients discharged on carvedilol compared to patients not on carvedilol.²⁵

One benefit of continuing beta-blocker therapy throughout hospitalization may be the higher rate of adherence upon discharge, given the difficulty of resuming beta-blockers once they are discontinued. Higher usage of beta-blockers has been observed in patients whose medication was not discontinued during an acute decompensated heart failure hospitalization.²⁶ The benefit of maintaining beta-blocker therapy during hospitalization may be associated with the difficulty patients face in reaching target dosages. In the CHAMP-HF registry, just 20.3% of patients with heart failure with reduced ejection fraction were prescribed target doses of beta-blockers at baseline, improving to only 26.4% after 12 months.¹⁸ The suboptimal beta-blocker dosage prescriptions may be due to the “start low, go slow” approach recommended when prescribing beta-blockers.²⁷ Given the time needed to achieve optimal dosages, the choice to withdraw or decrease beta-blocker therapy during hospitalization takes on greater importance. A single hospitalization has the potential to undo months or years of careful titration.

Initiation of Beta-Blocker Therapy Is Recommended in Beta-Blocker–Naïve Patients

Beta-blocker–naïve patients should be started on beta-blocker therapy during an acute decompensated heart failure hospitalization because initiation during hospitalization consistently benefits patients. A 2018 analysis of 672 beta-blocker–naïve patients who were hospitalized for acute decompensated heart failure and received inotropes showed that the predischarge initiation of beta-blockers resulted in lower 2-year mortality (21.3% vs 39.3%).²⁸ The authors also found that predischarge prescriptions of beta-blockers in beta-blocker–naïve patients resulted in significantly higher prescription rates after 12 months (89% vs 25%).²⁸ In an analysis of OPTIMIZE-HF, Fonarow et al found that initiation of beta-blockers during a heart failure hospitalization was well tolerated, as evidenced by 91.9% of patients maintaining therapy at 60 to 90 days postdischarge follow-up.²⁴

Professional societies also recommend initiating beta-blocker therapy during acute decompensated heart failure hospitalizations in beta-blocker–naïve patients. The 2021 European Society of Cardiology (ESC) guidelines state, “In patients admitted with AHF [acute heart failure], beta-blockers should be cautiously initiated in hospital, once the patient is haemodynamically stabilized.”⁴ The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) guidelines concur: “Oral GDMT [guideline-directed medical therapy] should not be withheld for mild or transient reductions in blood pressure.” The AHA/ACC/HFSA guidelines continue, “True contraindications are rare, such as advanced degree atrioventricular block….”⁹

Despite these encouraging findings, physicians should carefully monitor symptoms when initiating beta-blocker therapy. The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) found that the most common limiting factor for reaching target dosages of metoprolol CR/XL in the outpatient setting was low heart rate, seen in 11.3% of patients.²⁹ MERIT-HF also found that the greatest risk for mortality or hospitalization occurred 4 to 8 weeks following initiation of beta-blockers. After 8 weeks, rates of deterioration shifted to favor beta blockade in all patients taking beta-blockers. Patients’ subjective well-being could even predict future events. Lainscak et al found that self-reported health was an independent predictor of adverse events in patients with chronic heart failure during the period of initiating or increasing beta-blocker dosages.³⁰

Consider Withholding Beta-Blocker Therapy in Patients With Persistent Hypotension

In patients with persistent hypotension, physicians should consider withholding or reducing the dosage of beta-blocker therapy. To our knowledge, no studies have compared continuation vs withdrawal of beta-blocker therapy in acute decompensated heart failure patients with unresolved hypotension. However, professional guidelines recommend that physicians consider withholding beta-blockers or reducing the dosage while resolving persistent hypotension. The 2021 ESC guidelines state, “In those admitted with ADHF [acute decompensated heart failure], oral OMT [optimal medical therapy] should be continued, except for possible dose reduction or withdrawal if there is haemodynamic instability (symptomatic hypotension), severely impaired renal function or hyperkalaemia. Once haemodynamic stabilization is achieved with i.v. therapy, treatment should be optimized before discharge.”⁴ The 2022 AHA/ACC/HFSA guidelines state, “Withholding or reducing beta-blocker therapy should be considered in patients with marked volume overload or marginal low cardiac output.”⁹