Update on pharmacological treatment of heart failure

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)

CONSENSUS 253 NYHA class IV patients

3% β-blocker/53% MRA

SOLVD-T 2569 mainly NYHA class II/III patients

7% β-blocker

Placebo

Enalapril

RRR 27% P=0.003

Mo

rtal

ity

(%)

Months

0 1 2 3 4 5 6 7 8 9 10 11 12

20

40

60

80

0

Placebo Enalapril

RRR 16 (5-26)% P=0.0036

Mo

rtal

ity

(%)

Months

0 6 12 18 24 30 36 42 48

20

40

60

80

0

The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429-1435. The SOLVD Investigators. N Engl J Med. 1991;325:293-302.

Trials comparing an ACE inhibitor to placebo in patients with HF-REF

Total Sudden

p=0.001 p=0.04

US Carvedilol

(n=1014)

Total Sudden

CIBIS-II

(n=2647)

p=0.0001 p=0.001

Total Sudden

MERIT-HF

(n=3991)

p=0.0001 p=0.0002

3.2% 1.7%

7.8%

3.8%

7.2%

10.8%

3.9%

6.6%

11.8%

17.3%

3.6%

6.3%

Effects on total mortality and sudden

death in patients with HF-REF

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

RALES 1663 NYHA class III/IV patients

95% ACE-I/10% β-blocker

EMPHASIS-HF 2737 NYHA class II patients

93% ACE-I or ARB/87% β-blocker

RRR (95% CI) 22 (5-36)% P = 0.0139

Eplerenone

Placebo

Placebo

Spironolactone

RRR (95% CI) 30 (18-40)% P < 0.001

Pro

bab

ility

of

surv

ival

Years from randomization 0 1 2 3

0.50

0.70

0.80

0.90

0.00

1.00

0.60 P

rob

abili

ty o

f su

rviv

al

Years from randomization 0 1 2 3

0.50

0.70

0.80

0.90

0.00

1.00

0.60

Pitt B, et al. N Engl J Med. 1999;341:709-717. Zannad F, et al. N Engl J Med. 2010;364:11-21.

Trials comparing an aldosterone/MR antagonist to

placebo (added to an ACE-I and a BB) in HF-REF

Pharmacological treatments indicated in potentially all patients with symptomatic (NYHA class II–IV) HF-REF

AP Maggioni, Belgrade May 19, 2012

Agenda



• other treatments with less-certain benefits

HF-REF Other treatments with less-certain benefits

CHARM-Added and Val-HeFT

0

10

20

30

40

50

CHARM Val-HeFT

Placebo ARB

42.3%

37.9% 29.5%

25.9%

HR 0.85

95% CI 0.75-0.96

P=0.011

HR 0.86

95% CI 0.77-0.95

P=0.004

%

CV death or HF hospitalisation


HF-REF: Drug treatment 2012 (2)



AP Maggioni, Belgrade May 19, 2012

NNT = 56

ARR = 1·8%

adjusted HR (95·5% CI)* 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

0.4

0.3

0.2

0.1

0.0

0 6 12 18 24 30 36 42 48 54

Pro

ba

bili

ty o

f d

ea

th

Months since randomization

*Cox proportional hazards model adjusted for HF hospitalization in the previous year, prior pacemaker, and aortic stenosis

Pts at risk

n-3

Plac.

3,494

3,481 3,336

3,344 3,215

3,209 3,080

3,083

2,947

2,941

2,844

2,805

2,680

2,631

2,164

2,122

1,588

1,558

844

816

Placebo

1014/3481 (29·1%)

GISSI-HF n-3 PUFA: All-cause Death

n-3 PUFA

955/3494 (27·3%)

Agenda




• 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)




• 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 n. of

pts Drug Result

CHARM Preserved

3023 Candesartan Neutral

PEP-CHF 850 Perindopril Neutral

I-Preserve 4128 Irbesartan Neutral

Agenda






• Update on pharmacological treatment of co-morbidities

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






• Update on pharmacological treatment of co-morbidities

• Acute HF

Algorithm for management of acute pulmonary

oedema/congestion

ESC HF Pilot (2010-2011) 1-year all-cause mortality

(n. 5118 patients)

Days from enrollment

Chronic HF: 7.2%

Hospitalized HF: 17.4%

EURObservational Research Program

Initial assessment of patient with suspected acute heart failure

Documents

Update on pharmacological treatment of heart failure