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Heart Failure Management : 2013 Update. Richard Z Aramini, PharmD PGY-1 Pharmacy Resident February 19 th , 2014. Disclosure Statement. I, Richard Z Aramini, have nothing to disclose or possess any conflict of interest in this presentation. Objectives.
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Heart Failure Management:2013 Update Richard Z Aramini, PharmD PGY-1 Pharmacy Resident February 19th, 2014
Disclosure Statement • I, Richard Z Aramini, have nothing to disclose or possess any conflict of interest in this presentation.
Objectives • Be able to identify the basic pathophysiology of Heart Failure • Describe the efficacy and pharmacological effects of various agents used to manage HF • Employ a treatment plan for patients with various stages of HF
Take Home Messages • Be familiar with what’s new • Know when to use specific agents • Learn something interesting
Fundamentals “The minute you get away from fundamentals – whether its proper technique, work ethic or mental preparation – the bottom can fall out of your game, your schoolwork, your job, whatever you’re doing.” ― Michael Jordan
Overview • Epidemiology /Pathophysiology Review • Etiology of Heart Failure • Treatment by Stage • Changes from 2013 Guidelines • Review of Agents
Guidelines ACCF/AHA: The American College of Cardiology/ American Heart Association CCS: Canadian Cardiovascular Society ESC: European Society of Cardiology HFSA: Heart Failure Society of America
Epidemiology of Heart Failure • Lifetime risk: 20% for Americans >40 years of age • 20 per 1,000 individuals age 65-69 • >80 per 1,000 individuals age 85+ • 5.1 million Americans with clinical heart failure • >650,000 new cases diagnosed annually • Incidence has remained stable over last several decades • Relative Risk (NHANES I) • Coronary Heart Disease: RR: 8.1 • Diabetes: RR: 1.9 • Cigarette Smoking: RR: 1.6 • Hypertension: RR: 1.4 • Obesity: RR: 1.3 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Pathophysiology • Complex clinical syndrome resulting from structural or functional impairment of ventricular filling and the ejection of blood • Symptoms include: • Dyspnea • Fatigue • Fluid retention • No single diagnostic test
Pathophysiology McMurray JJ. N Engl J Med 2010;362:228-238
Pathophysiology 4 3 2 1 Schrier RW, Abraham WT. N Engl J Med 1999;341:577-585
Causes of Heart Failure • Cardiac Disorders • Pericardium • Myocardium • Endocardium • Heart Valves • Impaired left ventricular function • Cardiomyopathy • Dilated ventricle • Hypertrophic ventricle • Impaired Ejection Fraction • Heart Failure with Preserved Ejection Fraction • Heart Failure with Reduced Ejection Fraction 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Real Causes of Heart Failure • Ischemic Heart Disease • Majority of cases (50-60%) • Acute myocardial infarction • Hypertension • Present in 70-80% of patients • Suspected etiology in 30-40% of cases • Idiopathic dilated cardiomyopathy • 5-10% of patients • Other cardiomyopathy causes • EtOH, drug induced http://www.personal.psu.edu McMurray JJ, Pfeffer MA (2005). "Heart failure". Lancet365 (9474): 1877–89.
Staging of Heart Failure • American College of Cardiology Foundation/ American Heart Association (ACCF/AHA) • Emphasize progression of disease • Useful for describing individuals and populations • New York Heart Association (NYHA) • Focuses on exercise capacity and symptomatic status of disease
“A” as in All Right • Stage A • At risk for HF. No structural disease or symptoms • Manage patients risk factors • Hypertension • Thiazide diuretics • ACE Inhibitors • Hyperlipidemia • Lifestyle changes • Statins • Control/avoid conditions that may lead to HF • Obesity • Diabetes mellitus • Tobacco use • Use of known cardiotoxic agents
“B” as in Better Treat • Stage B • Structural Disease. No signs or symptoms • Often a patient with recent or remote MI or ACS • Initiate ACE Inhibitor • Prevent progression to symptomatic HF • Reduce mortality • ARB for ACEI intolerant • In ALL patients with reduced ejection fraction • Initiate Beta Blocker • Approved beta blockers • Metoprolol • Carvedilol • Bisoprolol • Reduce mortality • In ALL patients with reduced ejection fraction
Stage B Cont. • Start a Statin • In all patients with history of MI or ACS • Control Hypertension • Prevent LV hypertrophy • Avoid Nondihydropyridine Calcium Channel Blockers • Diltiazem • Verapamil • Harmful in asymptomatic patients
“C” as in Symptomatic • Stage C • Structural Heart Disease. Prior or current symptoms • Recommendations added to Stage B • Non-Pharmacologic Interventions • Patients should be educated about self care • Exercise training for those able • Sodium restriction • Continuous positive airway pressure
Class C Cont. • Diuretic Therapy • Loop diuretics • Patients with reduced ejection fraction • Symptomatic improvement • Aldosterone Antagonist • NYHA II-IV • Reduced ejection fraction • ACE Inhibitor + ARB • Persistently symptomatic • Those unable to use aldosterone antagonist
Class C Cont. • Hydralazine and IsosorbideDinitrate • African Americans • NYHA III-IV on optimal therapy • Digoxin • Beneficial in reduced ejection fraction • Reduce hospitalization
“D” as in Dyspnea at Rest • Stage D • Refractory heart failure • Specialized interventions • Water Restriction • 1.5-2 Liters per day • IonotropicSupport • Bridge therapy • Maintain end-organ performance • For patients awaiting definitive therapy
What’s New? • GDMT (guideline-directed medical therapy) • No longer “optimal medical therapy” • ACEI’s, BBs • Patient Education • Balanced view of sodium restriction • No strong evidence • May be beneficial in volume overloaded patients • Expanded use of aldosterone antagonists • Expanded use of MSC (mechanical circulatory support) • Intensified diuretic use in acute exacerbations HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-e194. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
GDMT 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Sodium Restriction • Previous Guidelines: • Dietary instruction regarding sodium intake is recommended in all patients with HF • Dietary sodium restriction (2-3 g daily) is recommended for patients with the clinical syndrome of HF • New Guidelines: • Sodium restriction is reasonable for patients with symptomatic HF to reduce congestive symptoms • Widely Embraced Idea • Not well supported by evidence • Particularly its effect on mortality HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-e194. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Mechanical Circulatory Support • First used in 1984 as bridge for transplantation • Recommended prior to definitive management • Carefully selected patients • Reduced ejection fraction • May be used as: • “Bridge to recovery” • “Bridge to decision” Kirklin J, NaftelD. Circulation. 2008 bio.felk.cvut.cz
Intensified Diuretics • Previous Guidelines: • When congestion fails to improve in response to diuretic therapy, the following options should be considered: • Re-evaluating presence/absence of congestion • Sodium and fluid restriction • Increasing doses of loop diuretic • Continuous infusion of a loop diuretic • Addition of a second type of diuretic orally or intravenously • New Guidelines: • Patients should be promptly treated with intravenous loop diuretics to reduce morbidity • Dose should equal or exceed their chronic oral daily dose • Be given as either intermittent boluses or continuous infusion • Add a second (thiazide) diuretic • Low-dose dopamine infusion may be considered HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-e194. 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Pharmacologic Agents • Diuretics • ACE Inhibitors • Angiotensin Receptor Blockers • Beta Blockers • Aldosterone Receptor Antagonists • Hydralazine and IsosorbideDinatrate • Digoxin • Miscellaneous Agents • Agents to avoid in Heart Failure 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Thiazide Diuretics • Benefit • Not potent enough for most HF patients • First line for hypertension • Mechanism of action • Blocks reabsorption of sodium and chloride in the distal tubule • When to use • Stage A • Added to loop diuretic therapy • Sequential nephron blockade • Contraindications • Anuria • Hypersensitivity
Thiazide(-like) Diuretics 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Loop Diuretics • Benefit • Symptomatic benefit only • Decrease sodium and water retention (preload) • Mechanism of action • Blocks Na-K-2CL co-transport of the ascending loop of Henle • When to use • Mainstay of HF diuretic therapy • Not mandatory • Contraindications • Anuria • Hypersensitivity 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Loop Diuretics • Potent fluid elimination • Less effective in controlling blood pressure • Patients should monitor weight daily • Report significant weight gain • Peripheral edema often not evident until ~10 lbs
Loop Diuretics 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Sequential Nephron Blockade http://3.bp.blogspot.com
ACE Inhibitors- Benefits • Reduce morbidity and mortality • Decrease preload and afterload • Decrease sympathetic activation • Prevent LV remodeling • Slows heart failure progression 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Mechanism of Action http://www.google.com
ACE Inhibitors • When to use • All patients with recent or remote MI or ACS • All patients with reduced EF • Part of guideline-directed medical therapy (GDMT) • Side Effects • Cough • Fluid overload, concomitant pulmonary disease, infection • Hyperkalemia • Reduced renal excretion • Acute Renal Insufficiency • Monitor BUN and SCr 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
ACE Inhibitor on Nephron http://www.google.com
ACE Inhibitors 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Angiotensin Receptor Blockers • Benefit • Similar to that of ACE inhibitor • Mechanism of action • Angiotensin II receptor antagonist • When to use • In ACE inhibitor-intolerant individuals • May be used in place of ACE inhibitors • In addition to ACE Inhibitor • Also on beta blocker • Aldosterone antagonist not indicated or tolerated • NOT TO BE USED with ACE inhibitor AND aldosterone antagonist
ARB Agents *Not indicated FDA indicated for heart failure 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Beta Blockers • Benefit • Reduces morbidity and mortality • Improves cardiac function • Increases EF • Improved exercise tolerance • Slows disease progression • Mechanism of action • Beta-adrenergic blockers selective for beta-1 receptors • When to use • GDMT • ALL patients with reduced EF • May be initiated in hospital after acute event 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Beta Blocker Agents • Likely worsening of symptoms initially • Increase SOB, weight gain • Slow titration upward • Over 6-8 weeks to target dose 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Aldosterone Antagonists • Benefit • Reduction in morbidity and mortality • Mechanism of action • Blocks distal renal tubules increasing Na and H20 excretion • Blocks effect on arterial smooth muscle • When to Use • NYHA II-IV • LVEF <35% • Creatinine <2.5 in men; <2.0 in women • eGFR > 30 ml/min • Potassium < 5.0 mEq/L • OR Following an acute MI with LVEF < 40% • Who develop symptoms • Have a history of diabetes 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Aldosterone Antagonists http://3.bp.blogspot.com/-
Aldosterone Antagonists • High mortality reduction when used appropriately • RR Reduction of Mortality: 30% • RR Reduction of Hospitalization: 35% • NNT: 6 Patients • DO NOT USE • SCr >2.5 in men; 2.0 in women • eGFR < 30 ml/min • Serum K > 5.0 mEq/L • In combination with ACEI and ARB 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Hydralazine & IsosorbideDinitrate • Benefit • Reduced morbidity and mortality • Reduces preload and afterload • Mechanism of action • Vasodilates arteries • Relaxes smooth muscle of vasculature • When to use • African Americans receiving optimal GDMT • NYHA Class III-IV • Patients who cannot tolerate ACE or ARB 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Hydralazine & IsosorbideDinitrate • Statistical Benefit • RR Reduction in Mortality: 43% • RR Reduction in Hospitalizations: 33% • NNT: 7 Patients *Target Dose: 175mg hydralazine/ 90mg isosorbidedinitrate 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852
Digoxin • Benefit • Improvement in symptoms • Improved exercise tolerance • Decreased number of hospitalizations • Mechanism of action • Positive ionotropic effect • Decreased sympathetic outflow • Improved baroreceptor function and vagal tone • When to use • Reduced ejection fraction • Symptomatic on optimal therapy • Target Concentration: 0.5-1.0 ng/ml 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:1810-1852