Heart Failure Update Hope or Hype?

Transcription

1 Heart Failure Update Hope or Hype? Laurajo Ryan, PharmD, MSc, BCPS, CDE Clinical Associate Professor The University of Texas at AusFn College of Pharmacy University of Texas Health Science Center Pharmacotherapy EducaFon Research Center Department of Medicine

2 I HAVE NO POTENTIAL FINANCIAL CONFLICTS TO DISCLOSE

3 Pharmacy Technician Learning ObjecFves IdenFfy the risk factors for heart failure Describe what consftutes a heart failure exacerbafon Recognize drug therapies common to pafents with heart failure List common drugs associated with heart failure exacerbafons

4 Pharmacist Learning ObjecFves Describe how newly approved treatments for heart failure fit into current therapy Develop a rafonal treatment plan for a pafent with decompensated heart failure Explain intervenfons to minimize the rate of readmission aoer a heart failure exacerbafon

5 Heart Failure Overview Cardiac output cannot meet demands of body Shortness of breath Edema Generalized fafgue/weakness ExacerbaFon New onset heart failure DeterioraFon of stable heart failure

6 EFology Eur Heart J 2013;34:1393

7 Heart Failure Death CDC/NCHS, NaFonal Vital StaFsFcs System mortality data,

8 HF Cause of Death CDC/NCHS, NaFonal Vital StaFsFcs System mortality data,

9 Heart Failure Spectrum HFrEF (systolic) Large dilated heart Decreased ejecfon fracfon (EF), cardiac output & Fssue perfusion Poor prognosis HFpEF (diastolic) Normal or increased ejecfon fracfon Venous pooling Prognosis beber vs. systolic

10 Pathophysiology CompensaFon ReacFon to decreased pumping capacity Increased preload Abempt to increase CO Na + & H 2 O retenfon RAAS, AVP, SNS, BNP, ANP Intended to be short term fix for acute reducfons Persistent decline in CO Long term acfvafon contributes to disease progression Nat Med 2005:11;828

11 Heart Failure CompensaFon Systems acfvated to increase cardiac output Renin angiotensin aldosterone system (RAAS) acfvafon SympatheFc acfvafon Increased vasopressin Increased counterregulatory hormones ANP, BNP Abridge RL, Miller ML, Moote RD, Ryan L, eds. Internal Medicine: A Guide to Clinical TherapeuFcs 1 st ed. New York, NY: McGraw-Hill; 2012

12 HF ExacerbaFon Causes Non-adherance Na + & H 2 O restricfons MedicaFon Noncompliance Inappropriate/inadequate therapy MedicaFon Cardiac events MI/ischemia CAD Atrial fibrillafon Anemia InfecFon

13 HF ExacerbaFon NegaFve inotropes AnFarrhythmics β-blockers Calcium channel blockers Verapamil DilFazem AnFfungals Itraconazole Terbenafine Cardiotoxic substances Ethanol Doxorubicin, daunomycin, cyclophosphamide, trastuzumab, imafnib Amphetamines Cocaine, methamphetamine Na + / H 2 O retenfon NSAIDs Thiazolidinediones GlucocorFcoids

14 PHARMACOTHERAPY

15 Vasodilators ACE inhibitors ARB Nitrates & hydralazine Beta-blockers Aldosterone antagonists Symptom control DiureFcs ± digoxin IntervenFons

16 ACE Inhibitors Improved hemodynamics & funcfonal status Improved survival Angiotensin receptor blockers (ARBs) Benefit similar to ACE inhibitors; recommended if ACE intolerant Long-acFng nitrate plus hydralazine Add on to standard therapy in African Americans Non-African American intolerant of ACE inhibitor/ ARB VasodilaFon Nat Rev Nephrol 2010;6,:319

17 Neprilysin Degrades vasoacfve pepfdes NatriureFc pepfdes, bradykinin, others

18 Neprilysin InhibiFon Increases nafurefc pepfdes & opposes neurohormonal acfvity

19 HFrEF LCZ696 (valsartan & neprilysin inhibitor) vs. enalapril Methods Double-blind RCT N = 8442 class II-IV HF EF 40% Primary outcome PARADIGM-HF Composite of CV death or hospitalizafon for HF N Engl J Med 2014;371;11

20 Results Trial mean f/u 27 months Primary outcome LCZ696 = 914 (21.8%) vs. enalapril = 1117 (26.5%) Hazard rafo 0.80; 95% CI 0.73 to 0.87; P<0.001 LCZ696 group > hypotension, nonserious angioedema < renal impairment, hyperkalemia, cough PARADIGM-HF N Engl J Med 2014;371;11

21 Conclusions LCZ696 superior to enalapril in reducing risk of death & hospitalizafon for HF PARADIGM-HF N Engl J Med 2014;371;11

22 Sacubatril & Valsartan (Entresto ) PotenFal to replace ACE inhibitor Contraindicated with ACEI HFrEF NYHA class II-IV LVEF 40% Stable SymptomaFc despite opfmal therapy Dosing Sacubatril/valsartan 24mg/26mg=50mg (~40mg valsartan) 49mg/51mg=100mg (~80mg valsartan) 97mg/103mg=200mg (~160mg valsartan)

23 Beta-Blockers Standard of care in stable HFrEF Improved survival & decreased HF progression Increase ejecfon fracfon Improve symptoms Do not inifate if decompensated ConFnue during hospitalizafon unless hemodynamically unstable NegaFve chronotrope Decreased heart rate Tolerability Asthma Blood pressure

24 HFrEF pafents Elevated HR Heart Rate Control Increase in morbidity & mortality Placebo group in SHIFT trial Risk of CV death or HF hospitalizafon 2.9% per 1BPM increase 15.6% per 5BPM increase HR <60bpm vs. >75bpm 32.4% decrease mortality & HF hospitalizafon

25 SA node produces pacemaker impulses Spreads to AV node triggering ventricular contracfon I f current IniFates diastolic depolarizafon of SA node HR RegulaFon

26 HCN channels HR RegulaFon HyperpolarizaFon-acFvated cyclic nucleofde-gated channels Regulate flow of I f current

27 Ivabradine I f inhibitor Binds to HCN channels use dependent SA node (f channels) Carries I f current prolongs diastolic Fme InhibiFon reduces heart rate ReFna (h channels) Carries I h current InhibiFon causes visual disturbances

28 Prolongs diastolic Fme Inhibits I f current, reducing heart rate Increases stroke volume Preserves myocardial contracflity BP Ivabradine Nat Rev Drug Disc 2006;5:1034

29 Ivabradine HFrEF pafents Elevated HR Increase in morbidity & mortality HR 87 BPM >2X risk for CV death or hospitalizafon for HF vs. HR BPM Hazard rafo 2.34, 95% CI , p < Elderly HFpEF pafents had symptomafc improvement & HR reducfon Eur Heart J 2013;34:suppl 1 CirculaFon 2001;103:1428 Lancet 2010;376:886

30 Ivabradine (Corlanor ) Approved to reduce hospitalizafon from HF Consider in HFrEF LVEF 35% ResFng heart rate 70 BPM On max dose of BB Or intolerant Titrate to resfng HR

31 Aldosterone Antagonists Aldosterone effects Na + & H 2 O retenfon Myocardial hypertrophy, fibrosis, vascular remodeling Aldosterone blockade Improved survival class III/ IV HFrEF Reduced pump failure & sudden cardiac death Benefit in early disease not as well established; consider if symptomafc on opfmal therapy Nat Rev Nephrol 2010;6,:319

32 Digoxin Mild posifve inotrope Decreases sympathefc acfvafon Symptom control Decreases hospitalizafon» Does NOT improve survival Mechanism Inhibits myocardial Na + K + ATPase pump Increased Ca ++ influx via Na + Ca ++ exchanger Increases cardiac contracfon SymptomaFc HFrEF on appropriate therapy Low dose

33 Pipeline Therapy RAAS acfvafon Long term remodeling ACEI, ARB, aldosterone antagonists have proven benefits Acute effects on hemodynamics & renal funcfon ACEI, ARB, aldosterone antagonists not appropriate for use in acute heart failure TRV027 β-arresfn biased ligand AT 1 R Allows blockade of AT2 VasoconstricFon, H 2 O, NA + retenfon SFmulaFon of β-arresfn Increased cardiac contracflity hbp://

34 JT 54 YO 2 nd hospitalizafon for HF exacerbafon in 3 months Past medical history Developed HFrEF aoer an MI in 2009 (LVEF <30%) Hypothyroidism OsteoarthriFs OutpaFent medicafons Metoprolol succinate, lisinopril, furosemide What else do you want to know?

35 CompensaFon in pafents with HF is detrimental because long-term it can cause: A. Sodium and water rentenfon B. Increased heart rate C. Cardiac remodeling D. All of the above

36 PaFents who require hospitalizafon for HF are likely to show which of the following symptoms? A. Shortness of breath B. Fluid overload C. Tachycardia D. All of the above

37 Which of the following pafents is likely to receive the most benefit from sacubatril/valsartan? A. Clinically stable pafent with HFpEF B. AsymptomaFc pafent with HFrEF C. Stable pafent with HFrEF and symptoms despite opfmal therapy D. PaFent with current HFrEF exacerbafon despite opfmal therapy

38 Which of the following pafents might be expected to receive benefit from ivabradine? A. 52 YO man with HFrEF and severe asthma B. 63 YO woman with HFrEF, BP 92/58mmHg, HR 82BPM on opfmal therapy C. 49 YO man with acute decompensated HF D. A & B only E. All of the above

39 Summary Current standards of care ACE inhibitors/arb Nitrates & hydralazine Beta-blockers Aldosterone antagonists Symptom control DiureFcs ± digoxin Newcomers Sacubatril/valsartan SymptomaFc despite opfmal therapy Intolerant to ACEI/ARB Ivadrabine Elevated HR despite opfmal BB therapy