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Systolic CHF Therapy

Systolic CHF Therapy. Rogers Kyle, MD 10/2/12. Learning Objectives. Review the staging and evaluation of patients with systolic heart failure Review the current guidelines for therapy of systolic heart failure

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Systolic CHF Therapy

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  1. Systolic CHF Therapy Rogers Kyle, MD 10/2/12

  2. Learning Objectives • Review the staging and evaluation of patients with systolic heart failure • Review the current guidelines for therapy of systolic heart failure • Identify the classes and dosing of medications used in the therapy of systolic heart failure

  3. 5 million people in US • 500,000 new cases annually • 1 million hospitalizations/yr as primary dx • 50,000+ CHF as primary dx deaths annually • 10 yr mortality almost 90% • Most frequent cause of hospitalization in the elderly • $38 billion, (over 5% of total healthcare cost)

  4. Staging • Stage A - high risk, no structural disease • HTN, DM, CAD, Obesity, met syn, cardiotoxins • Treat underlying med probs…ACE/ARB • Stage B - structural disease but no s/s CHF • LVH, ↓EF, MI, asymptomatic valvular disease • ACE/ARB, β-blocker • Stage C - structural disease with current or prior sx’s (NYHA I-IV) • Sx’c ↓EF or asymptomatic on Rx • Diuretics, ACE, β-blocker, also aldoantag, ARB, dig, hydral/nitrates • ICD, CRT • Stage D – refractory HF • Recurrent hosp despite Rx, need for transplant/VAD

  5. Physical Examination • Physical diagnostic accuracy (Escape Trial)

  6. CHF - Staging

  7. CHF - Staging

  8. CHF - Staging • Stage A – control risk • HTN • DM • Met Syn • Lifestyle mod (tob, etoh, drug abuse, etc.)

  9. CHF - Staging • Stage B • All of A • Recent MI – ACE, β-blocker • Reduced EF (no CAD) – ACE, β-blocker. ARB if ACE intol • Valvular disease • LVH – ACE/ARB • ICM - > 40 days p-MI, EF ≤ 30% → ICD • NO dig, CCB with (-) inotropy

  10. CHF - Staging • Stages C, D (refractory sx’s) • A, B • Diuretics, Na restrict if vol overloaded • ACE/ARB if ACE intol. ACE+ARB with ↓EF if still with sx’s on max rx (IIB) • β – Blocker – bisoprolol, carvedilol, metoprolol sustained release (succinate) • Aldosterone antagonist – preserved Cr (< 2.5), nl K+ • Hydralazine/nitrate – AA with continued CHF sx’s on optimal ACE, β-blocker, diuretics (level I) – all non-AA (level II) • Digoxin – reduced EF • ICD’s, CRT • NO ACE/ARB/Aldo antag combo, CCB

  11. CHF - Staging • Stages C, D (refractory sx’s) • A, B • Diuretics, Na restrict if vol overloaded • ACE/ARB if ACE intol. ACE+ARB with ↓EF if still with sx’s on max rx (IIB) • β – Blocker – bisoprolol, carvedilol, metoprolol sustained release (succinate) • Aldosterone antagonist – preserved Cr (< 2.5), nl K+…DM? • Hydralazine/nitrate – AA with continued CHF sx’s on optimal ACE, β-blocker, diuretics (level I) – all non-AA (level II) • Digoxin – reduced EF • ICD’s, CRT • NO ACE/ARB/Aldo antag combo, CCB

  12. ‘Order of Drugs’ • Loop diuretic • ACE/ARB • ACE vs. ARB; ACE + ARB? • β – Blocker • CIBIS-III – bisoprolol vs. enalapril first ( no difference) • After that…

  13. Diuretics • Studies date back to the 60’s (!) • Lasix most studied • Bumetanide, torsemide both better absorbed, torsemide lasts longer • Torsemide may have less readmissions (vs. lasix) for CHF (AJM 2001; 111(7):513) - ? Cost effective; now generic. Also, one observational study suggesting lower mortality (Eur J Heart Fail 2002; 4(4): 507)

  14. Diuretics • Dosing strategy (NEJM 2011; 364(9): 797) • Comparison of dose and route of administration of lasix in acute decompensated CHF • Low dose (equivalent to outpatient dose) or high dose (2.5 x outpatient dose) • Given as bolus Q12 or continuous infusion

  15. Diuretics • Other options? • Add thiazide • ? Ultrafiltration • Inotropes (milrinone - inc mortality) • Other – nesiritide (no mort/morbid benefit), VR2A (hypoNa+)

  16. ACE/ARB • Multiple trials have established benefit (sx’s and mortality) of ACE in all stages of CHF. • LVEF < 40% • Elderly, women, maybe less beneficial in AA but recommended • Less evidence for ARB’s but considered interchangeable (Cochrane Rev 2012)

  17. ACE/ARB • Choice of agent • Class effect • Enalapril most studied • Dosing • Usually started first • Less azotemia, hypotension if started at low doses • Enalapril 2.5 BID; captopril 6.25 TID; lisinopril 5 QD

  18. BUT…doses were high in the trials • Enalapril 10-20 BID; lisinopril 20-40 QD • Up-titrate doses every 2 weeks

  19. ARB • Recommended for same indications as ACE in pts intolerant of ACE • Intolerance does NOT include azotemia or hyperkalemia • BUT should be considered in angioedema in ACE • Add to ARB? • CHARM-Added (+) vs. Val-HeFT (-) vs. VALIANT (p-MI)

  20. 2009 Update • Consider adding to ACE in persistently sx’cpts with EF < 40% on conventional therapy • However… • EMPAHSIS – HF (eplerenone) • Routine use of ACE + ARB + aldoinhib is not recommeded • Dosing • Candesartan (most studied) – start at 4-8 mg QD, titrate to 32 mg QD • Valsartan 20-40 mg BID titrate to 160 mg BID • Losartan 25-50 mg QD titrate to 50-100 mg QD

  21. Beta Blockers • Demonstrated to reduce sx’sand hospitalizations and improve survival • Meta analysis 2001 AIM; > 20 trials, > 10,000 pts • Carvedilol (COPERNICUS); metoprolol ex release (MERIT-HF); bisoprolol (CIBIS) • 2005/09 • Current or prior CHF sx’s with reduced EF • ‘09 added – minimal or no evidence fluid retention, already on ACE

  22. Beta Blockers • Relative contraindications • HR < 60 • Hypotension • More than minimal fluid retention • Peripheral hypoperfusion • PR > 0.24, 2nd/3rd degree HB • Asthma • Resting LE ischemia from PVD

  23. Beta Blockers • Metoprolol - primarily β-1, some β-2 at doses > 100 mg • Start 12.5-25 mg QD, titrate to 200 mg QD • Carvedilol - non-selective β + alpha blockade • Start 3.125 mg BID, titrate to 25-50 mg BID • Bisoprolol - primarily β-1, some β-2 at doses > 20 mg • Start 1.25 mg QD, titrate to 5-10 mg QD

  24. Aldosterone Antagonists • Aldosterone levels tend to rise over time in pts on ACE/ARB • ?independent effect on structure/function • Emphasis- HF (RALES) (NEJM 2011; 364(1): 11) • Eplerenone added to usual rx • EF < 30-35%, NYHA II or more • 20% mortality benefit • Risk is K+ • Careful with NSAIDS, ACE/ARBS, DM, renal dys (Cr > 2.5), volume depletion • Do not use in combination with ACE + ARB • Start at 12.5 mg spironolactone, measure K+

  25. Hydralazine + Nitrates • Pre and afterload reduction • Early trials – • V-HeFT (hydralazine + nitrates similar to enalapril) • A-HeFT (+ enalaprilbeneficial in AA) • NYHA III, IV; EF < 40%, AA • 2005/09 • AA on diuretic/ACE/BB for NYHA II, III • Pts with sx’sdepsitediuretic/ACE/BB • Intol of ACE/ARB • Dosing • Start 25/20 mg TID; target 75/40 TID

  26. Digoxin • DIG trial • Reduced hospitalization, not mortality • 2005/09 • HYHA II, III, IV • EF < 40% • Sx’s despite diuretic/ACE/BB/aldo antag

  27. Summary

  28. References • Hunt SA et al. (2009) 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 119: e391-e479. • Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin receptor blockers for heart failure. Cochrane Database of Systematic Reviews (2012), Issue 4. Art. No.: CD003040. DOI: 10.1002/14651858.CD003040.pub2. • McAlister, FA, et al. 2009. Meta-analysis: -Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure. Ann Intern Med 150:784-794. • Willenheimer, R. et al. (2005) Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence :Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation 112: 2426-2435. • Zannad, F. et al. (2011) Eplerenonein Patients with Systolic Heart Failureand Mild Symptoms N Engl J Med 364 (1): 11-21.

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