Behandlungsalgorithmus bei Herzinsuffizienz mit reduzierter Auswurffraktion

Transcription

1 Behandlungsalgorithmus bei Herzinsuffizienz mit reduzierter Auswurffraktion Professor Dr. med. Roger Hullin Leiter Programm für Schwere Herzinsuffizienz, VAD & Herztransplantation Suisse Romande Klinik für Kardiologie Department Herz-Gefässe Universitätsklinik Lausanne DISCLOSURE: Research Grant NOVARTIS, VIFOR, Abbott

2 Treatment Algorythm Heart Failure with Reduced Ejection Fraction Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

3 High Dose vs Low Dose Lisinopril Treatment Effect on Mortality and Morbidity in Chronic Heart Failure N=3164 chronic HF pts in NYHA II-IV with LVEF 30% Time to Death Time to Death or Hospitalization for any reason HR= % CI: ; p=0.128 HR= % CI: ; p=0.002 Low dose= mg Lisinopril/d High dose= mg Lisinopril d Packer et al. Circulation 1999;100:

4 igh-dose group than in the low-dose therapy. These included cough in 13 pa whether a comprehensive High Dose orvscause- used. For Low Dose dizziness Lisinopril intreatment 43 patients, renal insufficienc Effect the prioritized on Mortality analysis and of Morbidity abnormal in Chronic values Heart for serum Failure potassium in on for any reason, patients in the Three months after randomization, sys a 12% lower risk than those in the had decreased mm Hg more a N=3164 chronic HF pts in NYHA II-IV with LVEF 30% TABLE 3. Effect of Treatment on Number of Hospitalizations Low-Dose High-Dose Percent Reduction in High-Dose Group Hospitalizations for any reason Hospitalizations for cardiovascular reason Hospitalization for heart failure Hospitalization for ischemic events P values are derived from the Wilcoxon rank sum test for between-group comparisons of the number of hospitalizations per patient. P ded from at Universite de Lausanne - CODUL on November 11, Packer et al. Circulation 1999;100:

5 High Dose vs Low Dose Lisinopril Treatment on Mortality and Morbidity in Chronic Heart Failure N=3164 chronic HF pts in NYHA II-IV with LVEF 30% Packer et al. Circulation 1999;100:

6 The CHARM-Alternative trial: effects of candesartan in HFrEF patients intolerant to ACE-inhibition N=2018 chronic HF pts in NYHA II-IV with LVEF 40% Kaplan-Meier cumulative event curves for cardiovascular death and HHF adjusted HR for cardiovascular death=0.8 Granger et al. Lancet 2003; 362:

7 Effects of high-dose versus low-dose loasartan on clinical outcomes in patients with HFrEF (HEAAL) N=3846 chronic HF pts in NYHA II-IV with LVEF 40% Kaplan Meier event curve for ACM & HHF Change in NYHA class Konstam et al. Lancet 2009;374:

8 Effects of high-dose versus low-dose losartan on clinical outcomes in patients with HFrEF (HEAAL) N=3846 chronic HF pts in NYHA II-IV with LVEF 40% Konstam et al. Lancet 2009;374:

9 Bisoprolol-first (o.d.) -blocker or ACE-inhibitor first? The CIBIS III - Study design mg mg Enalapril b.i.d. Bisoprolol o.d. Bisoprolol o.d. First up-titration Maintenance period Second up-titration Second maintenance period weeks week * * * * * * * * * * * * * * * *.. * 0 * 2 * 4 * 6 * Study end years * = visits Enalapril-first (b.i.d.) mg mg Bisoprolol o.d. Enalapril b.i.d Enalapril b.i.d First up-titration Maintenance period Second up-titration Second maintenance period weeks week 0 * 2 * 4 * 6 * 8 * 10 * * * * 30 * 32 * 34 * 36 * * * *.. Study end * * * * * years Willlenheimer et al. Circulation 2005;112:

10 -blocker or ACE-inhibitor first? -all cause mortality in CIBIS III 3-Länder-Treffen Wien 2018 % survival n=1010 pts with stable HF on diuretic treatment; 65 y, LVEF 35% Bisoprolol-first Enalapril-first B/E vs E/B 65 vs 73 deaths HR 0.88 (95% CI ) 12% risk reduction p=0.44 (difference) months Numbers at risk Willlenheimer et al. Circulation 2005;112:

11 Is there a target resting heart rate in CHF? -an analysis from COMET COMET: Metoprolol tartrate vs. Carvedilol in 3029 CHF with LVEF < 30% lower risk higher risk Metra et al. Eur Heart J 2005;26:

12 Is there a target dose of -blockade in CHF? -an analysis from MERIT-HF MERIT-HF: 3991 CHF-patients, NYHA II-IV, LVEF<40% Wikstrand et al. J Am Coll Cardiol 2002;40:491-8

13 Treatment Algorythm Heart Failure with Reduced Ejection Fraction Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

14 RALES The effect of spironolactone on morbidity and mortality in patients with severe HFrEF 3-Länder-Treffen Wien 2018 N=1663 pts with and NYHAIII/IV at enrollment and NYHA IV within the preceding 6 months HR=0.70; 95% CI ; p<0.0001) Pitt et al. NEJM 1999;341:

15 EMPHASIS-HF Effect of Eplerenone on Cardiovascular Mortality and HHF N=2737 pts, >55y, NYHA II, LVEF 30%, on maximal HF treatment Zannad et al. NEJM 2011;364:11-21

16 RALES Effect of race on safety and efficacy of spironolactone in patients with severe HFrEF 3-Länder-Treffen Wien 2018 n=120 afro-american pts vs non-aa patients Pitt et al. NEJM 1999;341:

17 Treatment Algorythm Heart Failure with Reduced Ejection Fraction Yancy et al. J Am Coll Cardiol 2018; 71:

18 BIOSTAT-CHF Determinants and clinical outcome of up-titration of ACE-I and beta blockers in HF 3-Länder-Treffen Wien 2018 n=2516; LVEF 40% or NT-proBNP >2000 pg/m Ouwerkerk et al. Eur Heart J 2017; 38:

19 Treatment Algorythm Heart Failure with Reduced Ejection Fraction Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

20 SHIFT Heart rate reduction with ivabradine for improvement of clinical outcomes N=6558 pts with stable CHF, optimal treatment and previous HHF <1y, and 70bpm 1117 Swedberg et al. Lancet 2010;376:

21 SHIFT Heart rate reduction with ivabradine for improvement of clinical outcomes Yancy et al. J Am Coll Cardiol 2018; 71:

22 ESC HFrEF Guidelines 2016 with an elevated plasma natriuretic peptide level (BNP 150 pg/ml or plasma NT-proBNP 600 pg/ml, or if HF hospitalization within recent 12 months plasma BNP 100 pg/ml or plasma NT-proBNP 400 pg/ml. In doses equivalent to enalapril 10 mg b.i.d. Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

23 PARADIGM-HF Primary and Secondary Endpoints McMurray et al. NEJM 2014;2:

24 Efficacy of LCZ696 vs. Enalapril when Drug Dose is Reduced In Heart Failure with Reduced Ejection Fraction Events prior to Dose Reduction Events after to Dose Reduction HR %CI: HR %CI: Vardeny et al. Eur J Heart Fail 2016;18:

25 Efficacy of LCZ696 vs. Enalapril at Lower than Target Dose In Heart Failure with Reduced Ejection Fraction HR of the Primary Outcome Measure by Time-updated Mean Post-Randomization Vardeny et al. Eur J Heart Fail 2016;18:

26 ESC Heart Failure Guidelines 2016 Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

27 Freedom from the combined endpoint 3-Länder-Treffen Wien 2018 Dosage of Heart Failure Medication Improves Outcome Following Cardiac Resynchronisation Therapy Β-blocker ACE / ARB Diuretics High dose Low dose Schmidt et al. Eur Heart J 2014;35:

28 ESC Heart Failure Guidelines 2016 Ponikowski et al. Eur Heart J 2016; doi: /eurheartj/ehw128

29 Impact of Carvedilol and Metoprolol on inappropriate implantable Cardioverter-Defibrillator Therapy 3-Länder-Treffen Wien 2018 n=1790 pts of the MADIT-CRT 556; a total of 253 inappropriate treatments Ruwald et al. J Am Coll Cardiol 2013;62:

30 Impact of Carvedilol and Metoprolol on VT/VF incidence in the MADIT-CRT study population 3-Länder-Treffen Wien 2018 n=1790 pts of the MADIT-CRT Kaplan-Meier estimates of ACM and HHF p=0.003) Ruwald et al. J Am Coll Cardiol 2013;61:

31 MERCI