Beta blockers for heart failure
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Beta blockers are the most effective therapy for heart failure according to clinical trials. Long term use of beta blockers such as bisoprolol, carvedilol, and sustained release metoprolol succinate can reduce mortality, heart failure hospitalizations, and improve ejection fraction and symptoms of heart failure. While initiation requires slow uptitration, discontinuation of beta blockers during heart failure hospitalization is generally not necessary and may worsen outcomes.
Beta blockers for heart failure
- 1. Beta blockers for heart failure Dr. Mahendra Cardiology ,JIPMER
- 2. Most hazardous drug Most effective therapy 1. Waagstein et al 1975 : Effect of chronic beta- adrenergic receptor blockade in congestive cardiomyopathy 2. Waagstein et al 1989 : Long-term beta-blockade in DCM.Effects of short- and long-term metoprolol followed by withdrawal and readministration of metoprolol. 3. CIBIS 1994 4. U.S. Carvedilol Heart Failure Study Group. 1996 N Engl J Med 5. CIBIS II. 1999 Lancet 6. MERIT-HF 2000 Β-Blocker status in chronic heart failure
- 3. Shift in paradigm is because of understanding of CHF Purely hemodynamic disease Activation of the deleterious neurohormonal systems and possibly inflammatory processes are responsible
- 4. Definitions I. Heart Failure with Reduced Ejection Fraction (HFrEF) - EF ≤ 40% II. Heart Failure with Preserved Ejection Fraction (HFpEF) - EF ≥50% a. HFpEF, Borderline – EF 41% to 49% b. HFpEF, Improved – EF >40%
- 5. Classification of Heart Failure ACCF/AHA Stages of HF NYHA Functional Classification A At high risk for HF but without structural heart disease or symptoms of HF. None B Structural heart disease but without signs or symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. C Structural heart disease with prior or current symptoms of HF. I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest. D Refractory HF requiring specialized interventions.
- 6. STAGE B HF (HFrEF) : Recommendations In all patients with a recent or remote history of MI or ACS and reduced EF, evidence-based beta blockers should be used to reduce mortality I IIa IIb III I IIa IIb III Beta blockers should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI.
- 7. • Data with beta blockers are less convincing in a population with known CAD, although in 1 trial carvedilol therapy in patients with stage B and low LVEF was associated with a 31% relative risk reduction in adverse long-term outcomes. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385–90.
- 8. Use of 1 of the 3 beta blockers proven to reduce mortality (i.e., bisoprolol, carvedilol, and sustained-release metoprolol succinate) is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality. STAGE C HF (HFrEF) : Recommendations I IIaIIb III Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–7.
- 9. STAGE C HF (HFpEF) : Recommendations The use of beta-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is reasonable to control blood pressure in patients with HFpEF I IIa IIb III
- 10. Maintenance of GDMT During Hospitalization • Initiation of beta-blocker therapy is recommended after optimization of volume status and successful discontinuation of intravenous diuretics, vasodilators, and inotropic agents. • Beta-blocker therapy should be initiated at a low dose and only in stable patients. • Caution should be used when initiating beta blockers in patients who have required inotropes during their hospital course. I IIa IIb III
- 11. Is Withdrawal of β-blockers necessary During HF Hospitalization ? • Continuation of beta blockers for most patients is well tolerated and results in better outcomes • Withholding of, or reduction in, β-blocker therapy considered only in pts hospitalized after recent initiation or increase in β-blocker therapy or with marked volume overload or marginal/low cardiac output Metra M, Torp-Pedersen C, Cleland JG, et al. Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. Eur J Heart Fail. 2007;9:901–9
- 12. β-Blockers in acute HF • Ionotropic agents – Last chance drugs • Abrupt stoppage of β-blockers paradoxical activation of the SNS , enhanced sensitivity to β- agonists • More severe the patient is, the more benefit from β-blocker therapy & more risk in stopping chronic β-blocker therapy • Hospitalization for acute HF: in-hospital mortality, short-term mortality, and combined mortality and hospitalization are lower when β- blockers are maintainedPrins et al .Effects of beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis.JACC 2015
- 13. Doses of Beta blockers commonly used for HFrEF Drug Initial Daily Dose(s) Maximum Doses(s) Mean Doses Achieved in Clinical Trials Beta Blockers Bisoprolol 1.25 mg once 10 mg once 8.6 mg/d (118) Carvedilol 3.125 mg twice 50 mg twice 37 mg/d (446) Carvedilol CR 10 mg once 80 mg once --------- Metoprolol succinate extended release (metoprolol CR/XL) 12.5 to 25 mg once 200 mg once 159 mg/d (447)
- 14. • Current data do not support a difference between selective and nonselective β-blockers. • Of note, the lipophilic β-blockers may be more beneficial than hydrophilic β-blockers in reducing the risk of sudden death.
- 16. Nebivolol • Beta-1 selective blocker nebivolol demonstrated a modest reduction in the primary endpoint of all-cause mortality or cardiovascular hospitalization • But did not affect mortality alone in an elderly population that included patients with HFpEF • 1.25 mg o.d. to target dose 10 mg o.d. SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol. 2009;53:2150–8.
- 17. Benefits of beta blockers Long-term treatment with beta blockers can •Lessen the symptoms of HF •Improve pt’s clinical status and •Enhance pt’s overall sense of well-being •Reduce the risk of death and the combined risk of death or hospitalization Benefits irrespective of CAD,DM,Sex and race MDC trial, CIBIS study, PRECISE trial, MERIT-HF
- 18. Beta blockers for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs GDMT RR Reduction in Mortality NNT for Mortality Reduction (Standardized to 36 mo) RR Reduction in HF Hospitalizations ACE inhibitor or ARB 17% 26 31% Beta blocker 34% 9 41% Aldosterone antagonist 30% 6 35% Hydralazine/nitrate 43% 7 33%
- 20. Greater improvement of symptoms and clinical status (NYHA class and overall well- being) in pts with moderate to severe symptoms than in those with mild symptoms
- 21. Beta Blockers: Initiation and Maintenance • Initiated at very low doses • Gradual increments in dose if lower doses have been well tolerated • Vital signs and symptoms – monitored closely • 85% of pts able to tolerate and achieve max planned trial dose with this approach • Can be safely started before discharge even in patients hospitalized for HF • Long-term treatment should be maintained, even if symptoms do not improve
- 22. Start slowly, but start JACC. 2004;43:1534
- 23. Caution • In pts with a current or recent history of fluid retention, beta blockers should not be prescribed without diuretics • Beta blockers may be considered in patients who have reactive airway disease or asymptomatic bradycardia but should be used cautiously in patients with persistent symptoms of either condition • Abrupt withdrawal of treatment with a beta blocker can lead to clinical deterioration and should be avoided
- 24. Risks of beta blockers 1) Fluid retention and worsening HF 2) Bradycardia or heart block 3) Hypotension 4) Fatigue
- 25. AF and HF • For pts who develop HF as a result of AF, a rhythm control strategy should be pursued • In pts with HF who develop AF, a rhythm- control strategy has not been shown to be superior to a rate-control strategy • β-blockers are the preferred agents for achieving rate control Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667–77
- 26. Major clinical trials of therapeutic interventions in pts with HFrEF
- 28. META-ANALYSIS Of 15 smaller trials plus the MDC, CIBIS and carvedilol trials included 3,023 patients. β-blockers 1. Reduced all-cause mortality by 32 % (P = 0.003) 2. Reduced the combined risk of death or hospitalization because of heart failure by 37 % (P < 0.001) 3. Increased the EF by 29% (P < 10-9 )
- 30. Conclusion • β-B are currently the cornerstone in HF therapy • Bisoprolol,Carvedilol and SR metoprolol succinate – currently approved β-B for HF • Uptitrating to max dose achieved in clinical trials necessary to achieve max benefit • Withholding β-B not necessary in HF hospitalisation