Update on pharmacological treatment of heart failure Aldo Pietro Maggioni, MD, FESC ANMCO Research Center Firenze, Italy
Presenter Disclosures Dr. Maggioni : Serving in Committees of studies sponsored by: Amgen, Bayer, Abbott Vascular, Johnson & Johnson, Novartis Pharma AG
Agenda Systolic heart failure (NYHA class II-IV) treatment options
HF-REF: Drug treatment 2008
HF-REF: Drug treatment 2012 (1)
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 80 80 60 Placebo 60 40 20 RRR 27% P=0.003 Enalapril 40 20 Placebo Enalapril RRR 16 (5-26)% P=0.0036 0 0 0 1 2 3 4 5 6 7 8 9 10 11 12 0 6 12 18 24 30 36 42 48 Months Months The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429-1435. The SOLVD Investigators. N Engl J Med. 1991;325:293-302.
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=0.0001 p=0.001 p=0.0001 p=0.0002 Carvedilol Placebo Bisoprolol Metoprolol US Carv Program. N Engl J Med 1996;334:1349 1355 CIBIS-II. Lancet, 1999; 353:9 13 MERIT-HF. Lancet 1999; 353:2001 2007
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 0.90 0.90 Eplerenone 0.80 0.80 Placebo 0.70 Spironolactone 0.70 0.60 Placebo 0.60 0.50 0.00 RRR (95% CI) 30 (18-40)% P < 0.001 0 1 2 3 Years from randomization 0.50 0.00 RRR (95% CI) 22 (5-36)% P = 0.0139 0 1 2 3 Years from randomization Pitt B, et al. N Engl J Med. 1999;341:709-717. Zannad F, et al. N Engl J Med. 2010;364:11-21.
Pharmacological treatments indicated in potentially all patients with symptomatic (NYHA class II IV) HF-REF AP Maggioni, Belgrade May 19, 2012
Agenda Systolic heart failure (NYHA class II-IV) treatment options other treatments with less-certain benefits
HF-REF Other treatments with less-certain benefits
CHARM-Added and Val-HeFT CV death or HF hospitalisation 50 40 Placebo ARB % 30 20 10 42.3% 37.9% 29.5% 25.9% 0 CHARM HR 0.85 95% CI 0.75-0.96 P=0.011 Val-HeFT HR 0.86 95% CI 0.77-0.95 P=0.004
HF-REF Other treatments with less-certain benefits
HF-REF: Drug treatment 2012 (2)
HF-REF Other treatments with less-certain benefits
HF-REF Other treatments with less-certain benefits AP Maggioni, Belgrade May 19, 2012
Probability of death GISSI-HF n-3 PUFA: All-cause Death 0.4 0.3 0.2 0.1 adjusted HR (95 5% CI)* NNT = 56 ARR = 1 8% p value 0 91 (0 833 0 998) 0 041 unadjusted HR (95 5% CI) p value 0 93 (0 852 1 021) 0 124 Placebo 1014/3481 (29 1%) n-3 PUFA 955/3494 (27 3%) 0.0 Pts at risk n-3 Plac. 0 6 12 18 24 30 36 42 48 54 3,494 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 844 816
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
Treatments (or combinations of treatments) that may cause harm
Agenda Systolic heart failure (HF-REF) treatment options other treatments with less-certain benefits treatments not recommended Preserved ejection fraction (HF-PEF)
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
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
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
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)
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
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
Algorithm for management of acute pulmonary oedema/congestion
ESC HF Pilot (2010-2011) 1-year all-cause mortality (n. 5118 patients) Hospitalized HF: 17.4% Chronic HF: 7.2% Days from enrollment EURObservational Research Program
Initial assessment of patient with suspected acute heart failure