Drugs to treat heart failure (1).pptx

Drug Therapy for Heart Failure Jennifer Hofmann Pharmacology Objectives  a. Describe the pathogenesis of heart failure as it relates to drug therapy.  b. Describe the clinical features of patients with heart failure.  c. Compare and contrast the advantages, adverse effects, and disadvantages...

Drug Therapy for Heart Failure Jennifer Hofmann Pharmacology Objectives  a. Describe the pathogenesis of heart failure as it relates to drug therapy.  b. Describe the clinical features of patients with heart failure.  c. Compare and contrast the advantages, adverse effects, and disadvantages of the various drugs used to treat heart failure (ACE inhibitors, angiotensin receptor antagonists, beta blockers, carvedilol, digoxin, diuretics and spironolactone, eplerenone, vasodilators, nitrates, positive inotropic drugs, ivabradine, sacubitril/valsartan etc.)  d. Describe the recommendations for heart failure therapy at https://www.acc.org/education-and-meetings/products-and-resources/ guideline-education/heart-failure  e. Formulate a treatment plan for heart failure patients considering individual patient characteristics, etiology and stage, and general goals of therapy. Topic Background: What is HF?  A pathophysiologic state in which the heart is unable to pump blood at a rate sufficient to meet the body’s metabolic demands  Systolic and diastolic failure  Ischemic heart disease(coronary artery disease), diabetes mellitus and chronic HTN are common causes of HF – Other causes  Background; Pathophysiology  As cardiac function decreases compensatory mechanisms kick in to maintain cardiac output (Q) – Sympathetic nervous system is activated  Tachycardia and vasoconstriction – Renin-angiotensin aldosterone system  Increases in Na and fluid retention  increased preload  Vasoconstriction  increased afterload – Ventricular hypertrophy and remodeling  Predicts long term prognosis in HF Background Physiology: Other factors in HF – Neurohormonal such as Ang II, NE, aldosterone  Increase preload and afterload – Proinflamatory cytokines  Remodeling of the heart – Endothelin  vasocontriction  increases afterload and preload  Veins and arteries  Also, cardiotoxic – Natriuretic peptides  Balance the RAS by causing CONCEPT  Overall compensatory mechanisms may initially improve cardiac output but the increased demand on a failing heart can worsen the condition Classification and staging of heart failure –older classification  New York Heart Association Functional Classification I – cardiac disease without limitations of normal physical activity II- patients with cardiac disease with slight limitations of physical activity (ordinary physical activity) III- pts with cardiac disease results marked limitation of physical activity IV- inability to carry on any physical activity w/o discomfort (dyspnea at rest) Background: Signs and Symptoms  Right heart failure – Bloating, anorexia, abd. Pain – Peripheral edema, JVD, HJ reflux, hepatomegaly  Left heart failure – DOE, PND, orthopnea, cough, tachypnea – Bibasilar rales, gallops  Nonspecific findings – Exercise intolerance, fatigue, weakness, nocturia – Tachycardia, pallor, cyanosis and cardiomegaly Heart Failure (X-rays)  http://www.learningradiology.com/lectures/c ardiaclectures/chfppt.pdf Standard first line therapies for routine use  ACEI or ARBs or (sacubitril and valsartan)= Entresto  Beta Blockers  Diuretics – (loop for volume overload – mineralocorticoid (MRA) aldosterone antagonists)  SGLT2 Inhibitors – Names = dapagliflozin or empagliflozin  Others (second line) – Ivabradine (Corlanor) – Digoxin (for many pts) – Vasodilators Pharmacotherapy Goals     Improve quality of life Slow progression of disease Prolong survival Treat – HTN, DM, Dyslipidemia, CAD nd other underlying causes Background: Therapy Basics  Most patients with HF (current or prior symptoms) are managed with a combination of 3 drugs – Diuretic  Loop- started initially for volume overload  K+ sparing eg eplerenone – ACEI/ ARB or Angiotensin Receptor Neprilysin inhibitor (ARNI) – Beta blocker (most) – SGLT2 Inhibitor Class: ACEI and HF  ACEI – Cornerstone of therapy for HF – Effects:  Reduce preload and afterload and inhibit Ang II effects on myocardium  Improve symptoms, slow disease progression, and decrease mortality in heart failure  Can use post MI early or later – Drugs:  5-6 ACE inhibitors are approved for HF treatment at target doses  Class: ACE Inhibitors  Adverse effects – – – – – Cough Angioedema Hypotension K+ retention Worsening renal function (reduce dose of concomitant diuretic)  Contraindications Class: ARBs  Role: – ARBs should be used for HF pts who are intolerant of ACEI – Valsartan trial demonstrated reduced mortality and morbidity  need further data to define role more clearly Drug name: Entresto (sacubitril and valsartan) Tablets  MOA – ARB plus neprilysin inhibitor ( increases natriuretic peptides which are degraded by neprilysin) – *Now preferred first line agent to start with HF Pharm: Dosed orally BID (can be titrated)  Indications: reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.  ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. – AE/ CI:     Hypotension (18%) hyperkalemia (12%,), cough (13%) dizziness (6%) and renal failure/acute renal failure (5%, ) Angioedema (0.5%).  CI in pregnancy  Do not use w/ ACE or ARB! Class: Diuretics  Names/class: – Loop diuretics such as furosemide (Lasix), bumetanide, torsemide are preferred – Effects:  Decrease fluid retention in HF (pulmonary and peripheral edema)  Assessment of volume status  Indications: – Used in combination regimen – Who gets diuretics?  Evidence of volume overload Class: Loop Diuretics  MC is furosemide at low doses  to decrease weight by 0.5-1kg/day – Moderate sodium restriction  Adverse effects: – Hypotension – Electrolyte imbalances (Na+, K+, Mg++)  May use ACEI or K+ supplements, K+ dietary  DIGOXIN AND K+ be careful ***** – Azotemia (in hi doses) – Monitor electrolytes, renal function, volume status Class: Beta antagonists Beta Blockers (BB) and HF  Role in HF is to: – reverse sympathetic nervous system (baroreceptor mediated increase in sympathetic activity) activation and – neurohormonal (renin angiotensin aldosterone) activation  HF beta blockers: – Names: Bisoprolol, metoprolol succinate – Alpha/beta blocker Names: carvedilol (Coreg po)  What do Beta-Blockers do? – Effects: Lessens sxs, improves status, and may reduce risk of death and hospitalization – Indications:  Start after initiated after optimal treatment w/ other first line med Class: B-blockers and HF  Pharm: – Start low and titrate to target  AE: – – – – – Worsened HF and fluid retention Fatigue, depression Bradycardia and heart block Hypotension Impotence CLASS: Aldosterone antagonists aka MRAs  Mineralocorticoid (MRA) Aldosterone antagonists  – Name:  spironolactone &  eplerenone (Inspra) which is More selective aldosterone antagonists  Indications – Recent or current class IV symptoms who are taking ACEI and other meds – Stages II- IV heart failure with reduced ejection fraction and symptoms despite other therapies  AE and C/I : – Hyperkalemia (use in pts with K+ < 5) – ACEI and ARBs- very careful to monitor for hyperKALEMIA!!! – Can cause gynecomastia in men (SPIRONO) Class: Sodium-glucose co-transporter 2 inhibitors  Names: – dapagliflozin or empagliflozin (PO)  MOA: see DM lecture  Indications – Add at any time to usual therapies as first line for HF  AE/ Precautions – UTIs, Genital infections  (rare Fournier’s Gangrene) – Monitor kidney function and BP! – Risk of lower extremities amputations – Rare DKA  Contraindications – Type 1 DM,  Presence of type 2 DM with prior diabetic ketoacidosis (DKA Class: Digitalis NAME: DIGOXIN  MOA: – positive inotropic agent by inhibiting Na/K+ ATPase leading to increased intracellular Ca++ and muscle contraction – Other actions  Effects: Reduced combined risk of death and hospitalization  Indications – Less frequently but can be used in conjunction with ACEI and BB to improve sxs and clinical HF status Digoxin- cellular mechanism http://www.cvpharmacology.com/cardiostimula tory/digitalis.htm figure from above Class/ drug: Digoxin and HF  Pharm: – Start and maintain at 0.125 mg –0.25mg /day  AE/ toxicity: – Cardiac arrhythmias (heart block, reentry, ventricular triggered activity) – Anorexia, N/V/ diarrhea – Neurological  visual, confusion, disorientation – Visual ( yellow halos, blurred vision, photophobia) – Narrow Therapeutic index – Drug interactions are NUMEROUS – Monitor K+, Mg2+, renal, EKG – Can use DigiBind to block DIG toxicity Drugs: Hydralazine and isosorbide dinitrate  Combination drug –  Indications: May be used for pts intolerant of ACEI MOA:  –  Study in black patients with stage III and IV heart failure Combination has complementary vasodilating effects – may have further mechanisms AE: Poorly tolerated Cardiovascular: Chest pain (16%) Central nervous system: Headache (50%), dizziness (32%) Neuromuscular & skeletal: Weakness (14%) May cause a drug-induced lupus-like syndrome Drug Name Corlanor® (ivabradine  Corlanor® (ivabradine  MOA:  https://www.corlanorhcp.com/mechanism-of-action/  Indication:  Add on or substitute for Beta blocker in patients with left ventricular heart failure in normal sinus rhythm and heart rate > 70bpm to reduce hospitalization  AE: – – – – bradycardia (10% vs. 2.2%), hypertension or increased blood pressure (8.9% vs. 7.8%), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena (phosphenes) or visual brightness (2.8% vs. 0.5%) NON PHARM THERAPY Restrict sodium intake: the Heart Failure Society of America guidelines recommend dietary sodium restriction (2-3 g/day) in all patients with HF and further restriction (<2 g/day) in those with moderate-to-severe HF. • Restrict fluid intake to <2 L/day in patients with hyponatremia. • Caloric supplementation should be provided to patients with advanced HF with weight loss and muscle wasting due to cardiac cachexia. • For patients with coexisting obstructive sleep apnea, continuous positive airway pressure (CPAP) is often recommended after polysomnography, thereby reducing systolic blood pressure and improving LV function. • Cardiac rehabilitation is unfortunately an underused preventive measure, although it has been shown to reduce morbidity and mortality. • Clinical: HF and Hospitalization Recommendation Clinical Scenario Hospitalization recommended ADHF with hypotension, worsening renal function, altered mental status Dyspnea at rest: resting tachypnea or oxygen saturation <90% Hemodynamically significant arrhythmia including new-onset atrial fibrillation Acute coronary syndromes Hospitalization should be considered Worsened systemic or pulmonary congestion without dyspnea or weight gain Major electrolyte disturbance Comorbid pneumonia, suspected pulmonary embolism, diabetic ketoacidosis, stroke Implantable cardioverter-defibrillator firing Previously undiagnosed HF with signs of systemic or pulmonary congestion Topic: Tx of Acute Decompensated HF  Hospitalized pts with severe decompensated HF may receive :  Drug: Dobutamine infusions or  Drug: Milrinone (Primacor) – MOA: lIV vasodilator/ positive inotropic agents as IV infusions – Main goal is short term therapy than covert to usual HF oral meds but some end stage HF patients use outpatient infusions – AE:  Ventricular arrhythmias, thrombocytopenia and hypersensitivity  DO not administer furosemide in IV lines with these 2 drugs precipitates form HF overall  Control blood pressure, angina management, diabetes mellitus and dyslipidemia  Manage SVTs and symptomatic ventricular arrhythmias (in select hi risk pts)  Monitor for efficacy & toxicity frequently Some Drug/ classes to AVOID with HF  1. Antiarrhythmic agents (74) can exert important cardiodepressant and proarrhythmic effects. Of available agents, only amiodarone has been shown not to adversely affect survival.  2. Calcium channel blockers (75) can lead to worsening HF and have been associated with an increased risk of cardiovascular events. Of available agents, only amlodipine has been shown not to adversely affect survival.  3. Nonsteroidal anti-inflammatory drugs (76) can cause sodium retention and peripheral vasoconstriction and can attenuate the efficacy, and enhance the toxicity, of diuretics and ACE inhibitors (77-79). References  http://www.acc.org/clinical/guidelines/failure/ hf_index.htm 

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