Medical Management of Heart Failure

Transcription

1 Medical Management of Heart Failure Louisville Symposium on Heart Disease in Women June 28, 2014 Andrew J. Lenneman, MD Assistant Professor of Medicine University of Louisville Division of Cardiovascular Medicine

2 Goals: Review guidelines based management for chronic heart failure therapy Discuss key trials used to develop heart failure treatment guidelines Discuss gender differences in heart failure

3 Heart Failure Deaths Slaughter, MS. Tex Heart Inst J, 2010

4 Women and Heart Failure Women are >50% of all CHF admissions CHF with preserved EF more common in women Nonischemic > Ischemic HTN, DM2, valvular disease HF associated depression is more common in women Unique causes: Peripartum cardiomyopathy Takotsubo cardiomyopathy Anthracycline induced cardiomyopathy

5 Women are under- represented in CHF trials Study Number of Women % Women MERIT- HF SOLVD Treatment SOLVD PrevenTon RALES EPHESUS DIG CIBIS II COPERNICUS CHARM - Overall CHARM - Preserved ELITE - II Val- HEFT COMPANION MIRACLE MUSTIC A- HEFT V- HEFT 0 0 CARE- HF

6 ~ 5-10% Hunt SA, et al. Circula(on 2001;104:

7 A Progression of Heart Failure Progression of Heart Failure B Arrhythmia CAD Diabetes Hypertension Cardiomyopathy Valvular disease Left ventricular injury Remodeling Low ejection fraction Death Pump failure neurohormonal swmulawon endothelial dysfuncwon vasoconstricwon renal sodium retenwon Non cardiac factors Symptoms Chronic heart failure Cohn JN; N EnglJ Med :490

8 IdenTfying the Stage B PaTent Echocardiography recommended for: CAD (ayer MI, revascularizawon) HTN, Valvular heart disease Family history of cardiomyopathy in 1 st degree relawve Atrial fibrillawon or flu_er EKG with LVH, LBBB, or pathologic Q waves Goals: Prevent progression to symptomawc disease Prevent death Maintain an excellent quality of life Do no harm Circulation 2013; 128:

9 Stage C The Symptoms of HF Symptoms Dyspnea on exerwon or at rest Declining exercise tolerance Orthopnea PND or nocturnal cough Edema Ascites or scrotal swelling Less specific presentatons Wheezing or cough Unexplained fawgue GI complaints: early sawety, nausea/ vomiwng, abdominal discomfort Depression/delirium (especially in elderly)

10 Stage C Guidelines: Medical Treatment of symptomatc Heart Failure Reduced EF ACE inhibitors/arbs Beta blockers DiureWcs Aldosterone antagonists ISDN+Hydralazine Digoxin ICD + CRT Preserved EF DiureWcs ACE inhibitors/arbs Beta blockers if MI, HTN, or AF? Aldosterone antagonists? Sildenafil? Ranolazine (TOPCAT) Think about restrictive diseases (amyloidosis, HCM) and constriction 2013 ACCF/AHA Guideline for the Management of Heart Failure Circula(on 2013; 128:

11 Improving Mortality in HF Trials 18 SOLVD SAVE 1991 CIBIS MERIT-HF 1999 SCD-HeFT % Death at 1 year DiureWcs, Digoxin DiureWcs, Digoxin, ACEi DiureWcs, Digoxin, ACEi, B- Blocker DiureWcs, Digoxin, ACEi, B- Blocker, ICD

12 ACE inhibitors/arb in Heart Failure Bradykinin System Kininogen Angiotensin System Angiotensinogen Renin Endothelium Bradykinin Angiotensin I + Prostaglandins Nitric oxide Inactive peptide + + ACE Angiotensin II Vasodilation Vasoconstriction! aldosterone Cell growth VanderbiltHeart.com

13 ACEi: Does dose maaer? The ATLAS trial TABLE 2. Effect of Treatment on Major Clinical Events Low-Dose High-Dose Hazard Ratio P All-cause mortality 717 (44.9) 666 (42.5) 0.92 ( ) Cardiovascular mortality 641 (40.2) 583 (37.2) 0.90 ( ) All-cause mortality hospitalization for any reason 1338 (83.8) 1250 (79.7) 0.88 ( ) All-cause mortality hospitalization for cardiovascular reason 1182 (74.1) 1115 (71.1) 0.92 ( ) All-cause mortality hospitalization for heart failure* 964 (60.4) 864 (55.1) 0.85 ( ) Cardiovascular mortality hospitalization for cardiovascular reason 1161 (72.7) 1088 (69.4) 0.91 ( ) Fatal and nonfatal myocardial infarction hospitalization for unstable angina 224 (14.0) 207 (13.2) 0.92 ( ) Values in parentheses indicate percentage or range. P values determined by log-rank test. Hazard ratios represent 95% CI, except for all-cause mortality, shown as 96.1% CI. *Analysis not specified in protocol before breaking the blind. Some is better than none Packer M et al. CirculaTon 1999;100:

14 ACE Inhibitors in Heart Failure Key points Start low dose, up- Wtrate to target doses from trials Check K+, creawnine within 1-2 weeks of each dose increase Minimize coincident ASA dose in nonischemics ContraindicaTons: Hx of life- threatening adverse effects Hypotension CreaWnine >3 g/dl Bilateral renal artery stenosis K+ 5.5 mmol/l

15 When to use ARBs in Heart Failure ACC/AHA Guidelines: Use as an alternawve when an ACEi is not tolerated (Class I) cough or angioedema Titrate dose similar to ACEi Evidence is mixed for ACEi + ARB CHARM- added vs. VALIANT Hypotension, worsening renal funcwon, hyperkalemia (Just like ACEi) Circulation. 2013;128:

16 Beta Blockers in Heart Failure How do Beta- Blockers Improve Heart Failure? UpregulaWon of beta receptors Improved coupling of beta receptors to intracellular signals AlteraWons in myocardial metabolism Improved calcium transport Increased protein synthesis and message expression InhibiWon of renin- angiotensin system InhibiWon of endothelin and cytokine release

17 Beta Blockers and Mortality in SAVE The best survival occurred with a Combination of ACE inhibitors And beta blockers Beta Blocker n=2231 pts Yes No Yes 13.3% 24.3% ACEi No 19.5% 27.7% N Engl J Med 1992 Sep 3;327:669-77

18 Outcome Trials of Beta Blockers in Heart Failure Trial Name Agent NYHA class % II/III/IV Hazard rato US carvedilol carvedilol 52/44/ CIBIS- II bisoprolol 0/83/ MERIT- HF metoprolol 41/56/ COPERNICUS carvedilol "severe" 0.65

19 . Beta Blockers in CHF: Does Dose Maaer? Bristow M R et al. Circulation 1996;94:

20 Beta Blockers in Heart Failure Key points Guidelines favor use of carvedilol, metoprolol succinate, bisoprolol Start at low dose, slowly up- Wtrate Aim to achieve target dose in 8-12 weeks Delay starwng if significant volume overload or hypovolemia/shock RelaWve contraindicawons: ReacWve airway disease, bradycardia, DM with recurrent hypoglycemia, reswng limb ischemia

21 DiureTcs in Heart Failure Rapidly improve symptoms of congeswon and lower cardiac filling pressures Deleterious Effects: AcWvate sympathewc nervous system and RAAS Electrolyte disturbances Decrease Cardiac output and GFR DiureWc resistance can be a marker of disease progression Don t forget about dietary sodium restricwon

22 JACC Vol. 59, No. 24, 2012

23 Aldosterone Antagonists N Probability of Survival R RALES- Advanced HF NYHA class III- IV LVEF<35% Months Spironolactone N EnglJ Med :709 Placebo Hospitalization for Heart Failure or Death from Cardiovascular Causes (%). at Risk EMPHASIS- HF NYHA class II Hazard ratio, 0.63 (95% CI, ) P<0.001 Placebo Years since Randomization Eplerenone N Engl J Med Jan 6;364(1):11-21

24 Aldosterone Antagonists Key Points NYHA class II- IV pawents with LVEF<35% Consider in most pawents with class II- IV CHF Following acute MI, with clinical HF or DM2 AND LVEF <40% (EMPHASIS- POST MI) K monitoring should be more rigorous in pawents at risk of hyperkalemia ContraindicaWons: Cr>2.5 mg/dl, K>5.0 mmol/l, elderly or cachewc pawents

25 Digoxin use in Heart Failure 50 Mortality from Any Cause (%) Placebo Digoxin P Months Overall Mortality The Digitalis Investigation Group: N EnglJ Med 336:525, 1997

26 30-d ay all-cause hospit tal admission Digoxin use in Heart Failure Number at risk Hazard ratio=0.66; 95% CI= ; p=0.002 Placebo Digoxin Follow-up p( (days) American Journal of Medicine (March 2013)

27 Digoxin use in Heart Failure No difference in mortality: serum level DIG trial Digoxin decreases hospitalizawons for CHF DIG trial Digoxin withdrawal results in worsening symptoms and exercise tolerance despite ACEIs RADIANCE Trial; PROVED Trial

28 What about Nitrates + Hydralazine? For pawents who develop hyperkalemia or renal dysfuncwon with ACE- I or ARB s Can be used IN ADDITION to ACE- I and β- blocker therapy in African- American pawents who have persistent NYHA class II- IV symptoms Overall Survival (%) No. at Risk Placebo Isosorbide dinitrate plus hydralazine P= Isosorbide dinitrate plus hydralazine Placebo Days since Baseline Visit N Engl J Med 2004;351: Circulation 2009, 119:e391-e479

29 HF management: More than just Drugs! Acute or chronic, reduced or normal EF NutriWonal counseling Sodium restricwon Fluid restricwon Alcohol Daily weights, symptom assessment, acwon plan Regular physical acwvity Compliance PaWents and family caregivers receive individualized educawon and counseling Frequent reinforcement emphasizing self care Early hospital follow up clinic + phone calls Cardiac Rehab/exercise training

30 Drugs to Avoid in Heart Failure NSAIDS Most anwarrhythmics Most Calcium channel blockers Felodipine, amlodipine are likely safe Thiazolidinediones Pioglitazone, rosiglitazone OTC Cold medicawon

31 Gender analysis of HF therapies Table 3. Effect of ACE Inhibitors on Mortality From Heart Failure in Male and Female Patients Reported Separately for Prevention Studies and Treatment Studies Analysis RR Male (95% CI) RR Female (95% CI) RRR (95% CI) Treatment (symptomatic) studies 0.80 ( ) 0.90 ( ) 1.15 ( ) Prevention (asymptomatic) studies 0.83 ( ) 0.96 ( ) 1.25 ( ) Abbreviations as in Table 2. RR Analysis Study-Name Total N Male N Female N RR Male (95% CI) RR Female (95% CI) CIBIS-II 2,647 2, ( ) 0.52 ( ) COPERNICUS 2,287 1, ( ) 0.63 ( ) MERIT-HF 3,991 3, ( ) 0.93 ( ) U.S. Carvedilol HF 1, ( ) 0.32 ( ) Random effects pooled estimate 7,885 2, ( ) 0.63 ( ) Abbreviations as in Table 2. Trial acronyms as in Abbreviation Box. J Am Coll Cardiol 2003;41:

32 Primary PrevenTon of Sudden Cardiac Death SCD-HeFT trial Placebo vs. Amio vs. ICD 0.4 Amiodarone vs. placebo ICD therapy vs. placebo Hazard Ratio (97.5% CI) 1.06 ( ) 0.77 ( ) P Value % Placebo (244 deaths; 5-yr event rate, 0.361) Mortality Rate Amiodarone (240 deaths; 5-yr event rate, 0.340) 34% ICD therapy (182 deaths; 5-yr event rate, 0.289) 29%, p No. at Risk Months of Follow-up Bardy N Engl J Med 2005;352:225-37

33 Primary PrevenTon of Sudden Cardiac Death in Heart Failure: ICD Consider ICD in all pawents with EF 35% with mild to moderate symptoms (NYHA II- III) Use cauwon in pawents with chronic, severe symptoms (NYHA IV) and life expectancy < 1 yr MADIT II, COMPANION, SCDHeFT all improve mortality ICDs are cost effecwve ($33,192/ life year added) 2013 ACCF/AHA Guideline for the Management of Heart Failure Circula(on 2013; 128:

34 Cardiac ResynchronizaTon Therapy Recommended for pawents with: Sinus rhythm on OMM QRS 120 ms (LBBB > RBBB) EF 35% NYHA III and ambulatory NYHA IV NYHA II, EF <30%, QRS>130 Improves funcwonal capacity Improves ventricular funcwon ( LVEF, EDD) Decreases hospitalizawons BiV pacing + ICD confers mortality benefit 2013 ACCF/AHA Guideline for the Management of Heart Failure Circula(on 2013; 128:

35 Chronic Heart Failure Management Take Home Points OpWmal medical and electrical therapy has improved survival considerably in heart failure Women are underrepresented in CHF trials but benefit from guidelines based treatments IdenWficaWon of the high risk pawent with heart failure is important to offer Wmely life saving intervenwons Use highest tolerated doses of Neurohormonal bockade a li_le is be_er than none CHF management is more than just drugs To have a global impact on the outcomes of heart failure, prevenwon and treatment of risk factors is be_er than a cure