Update on pharmacological treatment of heart failure. Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy

Transcription

1 Update on pharmacological treatment of heart failure Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy

2 Presenter Disclosures Dr. Maggioni : Serving in Committees of studies sponsored by: Amgen, Bayer, Abbott Vascular, Johnson & Johnson, Novartis Pharma AG

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4 Agenda Systolic heart failure (NYHA class II-IV) treatment options

5 HF-REF: Drug treatment 2008

6 HF-REF: Drug treatment 2012 (1)

7 Mortality (%) Mortality (%) Trials comparing an ACE inhibitor to placebo in patients with HF-REF CONSENSUS 253 NYHA class IV patients 3% β-blocker/53% MRA SOLVD-T 2569 mainly NYHA class II/III patients 7% β-blocker Placebo RRR 27% P=0.003 Enalapril Placebo Enalapril RRR 16 (5-26)% P= Months Months The CONSENSUS Trial Study Group. N Engl J Med. 1987;316: The SOLVD Investigators. N Engl J Med. 1991;325:

8 Effects on total mortality and sudden death in patients with HF-REF US Carvedilol (n=1014) CIBIS-II (n=2647) MERIT-HF (n=3991) Total Sudden Total 17.3% Sudden Total Sudden 3.2% 7.8% 1.7% 3.8% 11.8% 3.6% 6.3% 7.2% 10.8% 6.6% 3.9% p=0.001 p=0.04 p= p=0.001 p= p= Carvedilol Placebo Bisoprolol Metoprolol US Carv Program. N Engl J Med 1996;334: CIBIS-II. Lancet, 1999; 353:9 13 MERIT-HF. Lancet 1999; 353:

9 Probability of survival Trials comparing an aldosterone/mr antagonist to placebo (added to an ACE-I and a BB) in HF-REF Probability of survival 1.00 RALES 1663 NYHA class III/IV patients 95% ACE-I/10% β-blocker 1.00 EMPHASIS-HF 2737 NYHA class II patients 93% ACE-I or ARB/87% β-blocker Eplerenone Placebo 0.70 Spironolactone Placebo RRR (95% CI) 30 (18-40)% P < Years from randomization RRR (95% CI) 22 (5-36)% P = Years from randomization Pitt B, et al. N Engl J Med. 1999;341: Zannad F, et al. N Engl J Med. 2010;364:11-21.

10 Pharmacological treatments indicated in potentially all patients with symptomatic (NYHA class II IV) HF-REF AP Maggioni, Belgrade May 19, 2012

11 Agenda Systolic heart failure (NYHA class II-IV) treatment options other treatments with less-certain benefits

12 HF-REF Other treatments with less-certain benefits

13 CHARM-Added and Val-HeFT CV death or HF hospitalisation Placebo ARB % % 37.9% 29.5% 25.9% 0 CHARM HR % CI P=0.011 Val-HeFT HR % CI P=0.004

14 HF-REF Other treatments with less-certain benefits

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16 HF-REF: Drug treatment 2012 (2)

17 HF-REF Other treatments with less-certain benefits

18 HF-REF Other treatments with less-certain benefits AP Maggioni, Belgrade May 19, 2012

19 Probability of death GISSI-HF n-3 PUFA: All-cause Death adjusted HR (95 5% CI)* NNT = 56 ARR = 1 8% p value 0 91 ( ) unadjusted HR (95 5% CI) p value 0 93 ( ) Placebo 1014/3481 (29 1%) n-3 PUFA 955/3494 (27 3%) 0.0 Pts at risk n-3 Plac ,494 3,481 3,336 3,344 3,215 3,209 Months since randomization 3,080 3,083 2,947 2,941 2,844 2,805 2,680 2,631 2,164 2,122 1,588 1,558 *Cox proportional hazards model adjusted for HF hospitalization in the previous year, prior pacemaker, and aortic stenosis

20 Agenda Systolic heart failure (NYHA class II-IV) treatment options other treatments with less-certain benefits treatments not recommended Statins (neutral results of CORONA and GISSI-HF) Renin inhibitors (studies still ongoing) Oral anticoagulants other than in patients with AF Treatments that may cause harm

21 Treatments (or combinations of treatments) that may cause harm

22 Agenda Systolic heart failure (HF-REF) treatment options other treatments with less-certain benefits treatments not recommended Preserved ejection fraction (HF-PEF)

23 Pharmacological treatment of patients with HF-PEF (1) No treatment has yet been shown, convincingly, to reduce morbidity and mortality in these patients Diuretics are used to control sodium and water retention and relieve breathlessness and oedema Adequate treatment of hypertension and myocardial ischaemia is also considered to be important, as is control of the ventricular rate in patients with AF The drugs that should be avoided in HF-REF should also be avoided in HF-PEF, with the exception of CCBs

24 Pharmacological treatment of patients with HF-PEF (2) The key mortality morbidity trials to date are: Trial CHARM Preserved n. of pts Drug Result 3023 Candesartan Neutral PEP-CHF 850 Perindopril Neutral I-Preserve 4128 Irbesartan Neutral

25 Agenda Systolic heart failure (HF-REF) treatment options other treatments with less-certain benefits treatments not recommended Preserved ejection fraction (HF-PEF) Update on pharmacological treatment of comorbidities

26 Some new anticoagulants such as the oral direct thrombin inhibitors and oral factor Xa inhibitors are now available but they are contraindicated in severe renal impairment (creatinine clearance <30 ml/min)

27 Anaemia and iron deficiency Anaemia is associated with worse functional status, greater risk of HF hospitalization, and reduced survival Correctable causes should be treated in the usual way The value of erythropoietin-stimulating agents is unknown but is currently being tested in a large mortality morbidity RCT (RED-HF) Iron deficiency may independently contribute to muscle dysfunction in HF and causes anaemia FAIR HF evaluated 459 HF-REF patients (NYHA class II- III), a haemoglobin level 9.5 to 13.5 g/dl, and iron deficiency IV iron therapy improved self-reported patient global assessment IV iron may be considered as a treatment for these patients

28 Agenda Systolic heart failure (HF-REF) treatment options other treatments with less-certain benefits treatments not recommended Preserved ejection fraction (HF-PEF) Update on pharmacological treatment of comorbidities Acute HF

29 Algorithm for management of acute pulmonary oedema/congestion

30 ESC HF Pilot ( ) 1-year all-cause mortality (n patients) Hospitalized HF: 17.4% Chronic HF: 7.2% Days from enrollment EURObservational Research Program

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32 Initial assessment of patient with suspected acute heart failure