Balanced information for better care Heart failure: Managing risk and improving patient outcomes
Heart failure increases hospitalization Heart failure is the most common medical reason for hospitalization and the most costly diagnosis among Medicare patients. 1 FIGURE 1. Annual hospital admissions for common Medicare diagnoses 1 5, 4, Admissions 3, 2, 1, Heart failure Pneumonia COPD Arrhythmia Acute MI More than 16% of Pennsylvania residents over age 65 have heart failure (HF). 2 FIGURE 2. Treating heart failure is expensive. Total medical costs of HF topped $31 billion in 212, and are expected to exceed $7 billion by 23. 3 Direct medical costs = $21 billion 18% Morbidity Indirect medical costs = $1 billion 54% 14% Mortality Hospitalization 14% Outpatient 2 Heart failure
Heart failure is progressive Optimal management is based on stage and ejection fraction (EF): Heart failure with reduced ejection fraction (HFrEF) 4% EF systolic HF Heart failure with preserved ejection fraction (HFpEF) 5% EF diastolic HF FIGURE 3. Stages of heart failure guide appropriate management strategy. 4 STAGE DESCRIPTION GOAL STAGE A At risk for developing HF Prevent HF by treating risk factors. Prevention STAGE B Asymptomatic with structural heart disease* Treat with beta blockers and ACE inhibitors or ARBs to prevent progression to HF in patients with reduced EF. Heart failure STAGE C STAGE D Symptomatic prior or current symptoms of HF Refractory or advanced HF Use evidence-based treatments to reduce symptoms and improve outcomes. Refer to specialists for advanced therapies when indicated and discuss goal-directed care with patients. Source: American College of Cardiology Foundation and American Heart Association * Structural heart disease: left ventricular (LV) hypertrophy, LV dysfunction, prior myocardial infarction, or valvular disease ACE: Angiotensin-converting enzyme; ARB: Angiotensin receptor blocker Alosa Foundation Balanced information for better care 3
STAGE A: Patients at risk for developing heart failure Recognize and treat HF risk factors FIGURE 4. Risk factors for developing heart failure 5 Hazard ratio for developing HF 5 4 3 2 1 4.1 Coronary heart disease 3.5 Diabetes 3.2 LV hypertrophy 2.7 Valvular disease 2.3 Treated hypertension 2.1 Currently smoking Treat modifiable risk factors: comorbid conditions (e.g., coronary heart disease, hypertension, diabetes) behaviors (e.g., smoking, lack of physical activity, diet with excessive calories and/or salt) FIGURE 5. Treating blood pressure over 15 mmhg systolic resulted in a 64% decrease in HF in older patients. 6 7 HF episodes per 1 patients 6 5 4 3 2 1 p<.1 placebo treated 64 % 64 HF episodes per 1 people prevented by treating hypertension 1 2 3 4 Years of follow-up 4 Heart failure
STAGE B: Asymptomatic patients with structural heart disease Managing comorbidities benefits asymptomatic patients Patients with reduced EF require treatment: Begin with an ACE inhibitor. FIGURE 6. An ACE inhibitor reduces the risk of progression to HF or death in patients with low EF (<35%) by 29%. 7 5 placebo 4 p<.1 29 % Risk reduction Death or CHF (%) 3 2 1 enalapril 6 12 18 24 3 36 42 48 Months Use an ARB for patients who cannot tolerate an ACE inhibitor. Beta blockers also slow progression to HF by 14%. 8 Alosa Foundation Balanced information for better care 5
STAGE C: Symptomatic patients Symptomatic patients: Self care is critical monitoring signs and symptoms of HF (e.g., daily weights) limiting sodium exercising as tolerated (independently or in a cardiac rehabilitation program) adhering to the prescribed regimen FIGURE 7. Algorithm for pharmacologic treatment in HF with reduced EF INITIAL THERAPY ACE inhibitor (or ARB) loop diuretic for volume control beta blocker* Optimize ACE inhibitor / ARB and beta blocker doses CONTINUE IF SYMPTOMATIC aldosterone antagonist If GFR > 3 and K+ < 5 Stop ACEI or ARB and start sacubitril / valsartan Add digoxin and / or ivabradine Use ivabradine for patients with HR > 7 on maximally tolerated beta blockers African Americans with moderate to severe symptoms hydralazine / isosorbide dinitrate Refer to cardiology for consideration of advanced therapies * Trials enrolled patients with symptoms, but current guidelines recommend the use of beta blockers in most HF patients. Titrate ACE inhibitors and beta blockers to maximally tolerated dose to achieve the greatest mortality benefit. 9,1 Even a low dose of these drugs is better than no dose. 6 Heart failure
The quality of evidence varies by drug TABLE 1. Evidence summary for pharmacologic treatment of HF Medication Efficacy ref* pef** Target dose Monitor ACE inhibitor or ARB n highest tolerated dose while maintaining adequate BP serum potassium; renal function beta blocker (bisprolol, carvedilol, metoprolol XL) n highest dose tolerated for heart rate heart rate diuretics (bumetanide, furosemide, torsemide) n n as needed for symptom control volume status; serum potassium; renal function aldosterone antagonist (spironolactone, eplerenone) n serum potassium; renal function sacubitril / valsartan n highest tolerated dose while maintaining adequate BP serum potassium hydralazine / isosorbide dinitrate highest tolerated dose while maintaining adequate BP digoxin use lower doses in older patients renal function; digoxin level ivabradine highest tolerated for heart rate heart rate *ref = reduced EF, systolic HF **pef = preserved EF, diastolic HF Use ACE inhibitors before using an ARB. Reduces mortality and hospitalization Reduces mortality and hospitalization in African Americans No reduction in mortality or hospitalization No data available Reduces hospitalization but not mortality Other treatment options for patients with heart failure with reduced ejection fraction: Implantable cardioverter defibrillators (ICDs) improve survival in symptomatic HF patients and asymptomatic patients who are post myocardial infarction (MI). 11 In HF patients with prolonged QRS, cardiac resynchronization therapy (CRT) increases survival up to 36%. 12 Alosa Foundation Balanced information for better care 7
STAGE C: Symptomatic patients, continued New treatment options for symptomatic patients with reduced EF (ref) Sacubitril / valsartan FIGURE 8. In PARADIGM-HF, sacubitril / valsartan reduced mortality and hospitalization. 13 Ivabradine FIGURE 9. In SHIFT, ivabradine decreased hospitalization for worsening HF. CV death or HF hospitalization (%) 3 25 2 15 1 5 HR.8; p<.1 22 % sacubitril / valsartan 27 % enalapril Patients with first hospital admission for worsening heart failure (%) 3 25 2 15 1 5 HR.74; p<.1 placebo ivabradine 6 12 18 24 3 Months For patients with reduced EF who continue to be symptomatic on optimal medical therapy, sacubitril / valsartan replaces the ACE inhibitor or ARB. Ivabradine is limited to patients on maximally tolerated beta blocker therapy with heart rates > 7. 14 Managing patients with preserved EF (pef) Treat hypertension. Use diuretics to control symptoms: Monitor for hypovolemia and hypotension. Patients with preserved EF may be more sensitive to diuretics and dihydropyridine calcium channel blockers (e.g., amlodipine, nifedipine) than patients with reduced EF. Control heart rate in patients with atrial fibrillation. Treat symptomatic ischemic heart disease. 8 Heart failure
STAGE D: Refractory heart failure Weigh risks and benefits of advanced therapy: Discuss goals of care Half of patients admitted for HF are rehospitalized within 6 months. 15 Advanced or refractory HF care should focus on quality of life: determine if mechanical circulatory support is an option reduce time in the hospital review end of life goals when appropriate discuss palliative care if indicated Options for advanced therapy include: continuous infusion inotropes left ventricular assist device heart transplant FIGURE 1. More patients have been using hospice rather than hospital at the end of life. However, a growing proportion of hospitalized patients were in the ICU. 16 8 Care received at the time of death (%) 7 6 5 4 3 2 1 Intensive care unit (ICU) Non-ICU inpatient Hospice 2 21 22 23 24 25 26 27 Alosa Foundation Balanced information for better care 9
Costs FIGURE 11. Cost of a 3-day supply of medications used in managing heart failure metoprolol succinate (generic) 15mg $77 Beta blockers metoprolol (Toprol XL) 15mg carvedilol (generic) 37.5mg carvedilol (Coreg) 37.5mg carvedilol CR (Coreg CR) 4mg bisoprolol (generic) 1mg $1 $34 $123 $262 $364 bisoprolol (Zebeta) 1mg $162 ACE inhibitors lisinopril (generic) 1mg lisinopril (Zestril) 1mg enalapril (generic) 1mg ramipril (generic) 2.5mg ramipril (Altace) 2.5mg captopril (generic) 5mg $4 $6 $35 $33 $125 $375 candesartan (Atacand) 8mg $17 candesartan (generic) 8mg $84 ARBs losartan (generic) 5mg losartan (Cozaar) 5mg $37 $11 valsartan (generic) 8mg $127 valsartan (Diovan) 8mg $25 Diuretics Aldosterone antagonists spironolactone (generic) 75mg spironolactone (Aldactone) 75mg eplerenone (generic) 5mg eplerenone (Inspra) 5mg metolazone (generic) 5mg metolazone (Zaroxolyn) 5mg hydrochlorothiazide (generic) 25mg bumetanide (generic) 1mg torsemide (generic) 1mg torsemide (Demadex) 1mg $1 $44 $4 $27 $21 $66 $14 $114 $158 $24 furosemide (generic) 4mg $4 furosemide (Lasix) 4mg $29 digoxin (generic).25mg $34 digoxin (Lanoxin).25mg $224 Other drugs hydralazine+isosorbide dinitrate (Bidil) 112.5/6mg hydralazine (generic) 112.5mg isosorbide dinitrate (generic) 6mg ivabradine (Corlanor) 1mg $1 $81 $2 $383 sacubitril/valsartan (Entresto) 97mg/13mg $392 Prices from goodrx.com, November 215. Listed doses are based on Defined Daily Doses by the World Health Organization, and should not be used for dosing in all patients. 1 Heart failure 5 1 15 2 25 3 35 4
Key messages Identify risk factors for heart failure such as hypertension, diabetes, and atrial fibrillation and treat them to prevent or delay the development of heart failure. In HF with reduced EF, titrate beta blockers and either ACE inhibitors or ARBs to doses used in studies, or the maximally tolerated dose. Patients who have symptomatic HF with reduced EF even when on an ACE inhibitor or ARB may be candidates for sacubitril / valsartan (Entresto) to replace their ACE inhibitor or ARB. In HF with preserved EF, treat hypertension and manage other comorbidities to control symptoms. Diuretics are useful to maintain fluid balance in patients who have HF with both preserved and reduced EF. After HF hospitalization, address possible medication non-adherence, review weight goals, and reinforce salt or fluid restriction. Discuss goals of care and advance directives for patients with severe, end-stage HF. Visit alosafoundation.org/modules/heartfailure for links to additional resources and a longer evidence document References: (1) Centers for Medicare & Medicaid Services. Medicare Provider Utilization and Payment Data: Inpatient. www.cms.gov. Accessed November 2, 215. (2) CMS/Office of information products and data analytics. Medicare chronic conditions dashboard: state level. www.cms.gov/research-statistics- Data-and-Systems/Statistics-Trends-and-Reports/Dashboard/Chronic-Conditions-State/CC_State_Dashboard.html. Accessed September 22, 215. (3) Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 213;6(3):66-619. (4) Yancy CW, Jessup M, Bozkurt B, et al. 213 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 213;128(16):e24-327. (5) Agarwal SK, Chambless LE, Ballantyne CM, et al. Prediction of incident heart failure in general practice: the Atherosclerosis Risk in Communities (ARIC) Study. Circ Heart Fail. 212;5(4):422-429. (6) Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 8 years of age or older. N Engl J Med. 28;358(18):1887-1898. (7) The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327(1):685-691. (8) Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 21;357(9266):1385-139. (9) Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999;1(23):2312-2318. (1) Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation. 1996;94(11):287-2816. (11) Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 25;352(3):225-237. (12) Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 25;352(15):1539-1549. (13) McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 214;371(11):993-14. (14) Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 21;376(9744):875-885. (15) Desai AS, Stevenson LW. Rehospitalization for Heart Failure: Predict or Prevent? Circulation. 212;126(4):51-56. (16) Unroe KT, Greiner MA, Hernandez AF, et al. Resource use in the last 6 months of life among medicare beneficiaries with heart failure, 2-27. Arch Intern Med. 211;171(3):196-23. Alosa Foundation Balanced information for better care 11
About this publication These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient s clinical condition. More detailed information on this topic is provided in a longer evidence document at alosafoundation.org. The Independent Drug Information Service (IDIS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania. This material is provided by the Alosa Foundation, a nonprofit organization which is not affiliated with any pharmaceutical company. IDIS is a program of the Alosa Foundation. This material was produced by Jennifer Lewey, M.D., Research Fellow, Brigham and Women s Hospital; Michael A. Fischer, M.D., M.S., Associate Professor of Medicine (principal editor); Jerry Avorn, M.D., Professor of Medicine; Niteesh K. Choudhry, M.D., Ph.D., Associate Professor of Medicine, all at Harvard Medical School; and Ellen Dancel, PharmD, MPH, Director of Clinical Material Development at the Alosa Foundation. Drs. Avorn, Choudhry, and Fischer are physicians at the Brigham and Women s Hospital in Boston, and Dr. Lewey practices cardiology at the Columbia University Medical Center in New York. None of the authors accepts any personal compensation from any drug company. Medical writer: Stephen Braun. Copyright 215 by the Alosa Foundation. All rights reserved.