Heart failure: The national burden

AHA. Heart disease and stroke statistics–2005 update. Koelling TM et al. Am Heart J. 2004;147:74-8.

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• Affects 1 million Americans

• >550,000 new cases annually

• >53,000 deaths in 2002

• Leading Medicare hospital diagnosis

• >1 million hospitalizations annually

• Direct and indirect costs: $27.9 billion

ACC/AHA: Heart failure stages A and B

Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.

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Stage A

*Appropriate patients

Stage B

HypertensionCADDiabetesObesityMetabolic syndrome

Previous MILV remodelingLV hypertrophyLow EF

Patients

No structural heartdisease/asymptomatic

Structural heartdisease/asymptomatic

Definition

Treat BP, lipidsSmoking cessation Regular exercise Alcohol/drug use

All measures under stage A

Goals

ACEI or ARB for vascular disease/diabetes*

ACEI or ARB*-Blockers*

Therapy

ACC/AHA: Heart failure stages C and D

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Stage C

*Selected patients

Stage D

Shortness of breathFatigueExercise capacity

Marked symptoms at rest despite maximal therapy

Patients

Structural heart disease Prior/current symptoms

Refractory HFDefinition

All Stage A and BDietary salt restriction

All Stage A, B, and CDecision re: appropriate level of care

Goals

Routine drugs Diuretics ACEI -Blockers

Options Compassionate care/hospice

Drugtherapy

Devices* Biventricular pacingImplantable defibrillators

Selected patients Aldosterone antagonist ARBs Digitalis Hydralazine/nitrates

Extraordinary measures Heart transplant Chronic inotropes Permanent mechanical support Experimental surgery/drugs

Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.

CHARM: HF patients with LV dysfunction

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CHARM-Alternative CHARM-Added

Candesartan 32 mg/d vs placebo

Candesartan 32 mg/d vs placebo + ACEI and other HF therapy

Therapy

N = 2028LVEF ≤40%Intolerant to ACEI

N = 2548LVEF ≤40%Treated with ACEI

Patients

41 months 33.7 monthsFollow-up

23% RRR (P < 0.001)7% absolute

Primaryoutcome*

15% RRR (P < 0.011)4% absolute

Granger CB et al. Lancet. 2003;362:772-6.McMurray JJV et al. Lancet. 2003;362:767-71.

*CV mortality/HF hospitalizationRRR = relative risk reduction

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Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.

VALIANT: Study design

*<40% by radionuclide ventriculography (RVG)

Valsartan 160 mg 2/d (n = 4909)Captopril 50 mg 3/d (n = 4909)Captopril 50 mg 3/d + valsartan 80 mg 2/d (n = 4885)

Therapy

N = 14,703 with MI within ≤10 daysHF and/or LVEF <35%*

Patients

24.7 monthsFollow-up

VALIANT: Primary outcome—Death from any cause

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0.3

0.4

0.2

0.00 6 12 18 3624 30

0.1

Months

Probabilityof event

Valsartan*Valsartan plus captopril†

Captopril

*P = 0.98 vs captopril†P = 0.73 vs captopril Pfeffer MA et al. N Engl J Med. 2003;349:1893-906.

ACC/AHA recommendations: ARBs in patients with LV dysfunction

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Alternative therapy:Use ARBs approved for the treatmentof HF in patients witih current or prior HF symptoms who are ACEI intolerant

I

Class

A

Level of evidence

ARBs are reasonable alternatives to ACEI as first-line therapy for patients with mild to moderate HF, especially those already taking ARBs for other indications

IIa A

ARBs should be administered to post-MI patients without HF symptoms who are intolerant of ACEIs and have a low LVEF I B

Added therapy:Consider adding ARBs in persistently symptomatic patients with reduced LVEF who are already treated with conventional therapy

IIb B

Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.

CHARM-Added: Effects of adding candesartan to -blocker and ACEI

McMurray JVV et al. Lancet. 2003;362:767-71.

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Candesartan better

Placebo better

PlaceboCandesartan

-Blocker223/702 274/711260/574 264/561

Recommended doseof ACE inhibitor

232/643 275/648

YesNo

YesNo 251/633 263/624

All patients 483/1276 538/1272

0.6 0.7 0.8 0.9 1.0 1.1 1.2

0.14

0.26

*For treatment interaction

P*

Hazard ratio

HF with LV dysfunction: Patients, efficacy, and dosing considerations

Adapted from Hunt SA et al. J Am Coll Cardiol. 2005;46:1-82.

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ARB PatientsInitial

dose(s)EfficacyMaximumdose(s)

Candesartan HF 4–8 mg1/d

CV mortality HF hospitalizations

32 mg1/d

Valsartan HFPost-MI

20–40 mg2/d

CV mortality 160 mg2/d

CHARM: Prevention of diabetes with candesartan

Yusuf S et al. Circulation. 2005;112:48-53.

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10

12

8

6

4

2

00 1.0 2.0 3.0 3.5

Proportionof patients

(%)

Placebo

Candesartan

RRR = 22%HR = 0.78 (0.64–0.96)P = 0.020

n = 202 (7.4%)

n = 163 (6.0%)

Years

RRR = relative risk reduction