Heart Failure Treatments · 2019. 11. 18. · • Biggest beneﬁt in advanced disease Thursday, 10...

Heart Failure Treatments

Past & Present

www.philippelefevre.com

Thursday, 10 February 2011

Background

Chronic heart failure• Drugs

• Mechanical

• Electrical

Background

Chronic heart failure• Drugs

• Mechanical

• Electrical

Sudden cardiac death • Amiodarone

• Implantable Cardioverter-Defibrillator

Heart Failure

Big Problem

Prevalence over 65y = 4%

5 year mortality = 50%

Clasification

Systolic Vs Diastolic

Right Vs Left

Forward Vs Backward

High output Vs Low output

Acute Vs Chronic

Clasification

Right Vs Left

Forward Vs Backward

Acute Vs Chronic

Clasification

Right Vs Left

Forward Vs Backward

Acute Vs Chronic

Clasification

Right Vs Left

Forward Vs Backward

Acute Vs Chronic

Clasification

Right Vs Left

Forward Vs Backward

Acute Vs Chronic

Causes

Ischaemic Heart Disease 40%

Dilated Cardiomyopathy 35%

Hypertension 15%

Causes

Ischaemic Heart Disease 40%

Dilated Cardiomyopathy 35%

Hypertension 15%

• Undilated cardiomyopathy

• Valvular

• Cor pulmunale

• Congenital

• Alcohol and drugs

• Arrhythmia

Heart Failure

• Ventricular remodelling

• High filling volumes

• Fluid & salt retention

• Hypotension & under perfusion

• High circulating catecholamines

• Redirection of cardiac output

• High levels of ADH

• High levels and resistance to natriuretic peptides

• Arrhythmia

Ventricular Volumes

normal

LVEF: 65%

Ventricular Volumes

normal

LVEF: 65%

end-diastolicvolume

strokevolume

Ventricular Volumes

normal

LVEF: 65%

failure

end-diastolicvolume

strokevolume

Ventricular Volumes

normal

LVEF: 65%

failure

50% 30%

end-diastolicvolume

strokevolume

Treatment OptionsChronic Heart Failure

Underlying Problem

• Stop smoking

• Stop drinking

• Loose weight

• Exercise

• Diabetic control

• Blood pressure control

• Statins

• Valvuloplasty

• Revascularisation

• ACE inhibitors

• Angiotensin II receptor antagonists

• Beta blockers

• Aldosterone inhibitors

• Loop diuretics

• Cardiac glycosides

• Non glycoside inotropes

• Anti-arrhythmics

• Anticoagulation

• ACE inhibitors

• Angiotensin II receptor antagonists

• Beta blockers

• Aldosterone inhibitors

• Loop diuretics

• Cardiac glycosides

• Non glycoside inotropes

• Anti-arrhythmics

• Anticoagulation

Mechanical

• Biventricular pacing

• Intra aortic balloon pump

• Intra aortic propeller pump

• Left ventricular assist devices

reninangiotensinogen

reninangiotensinogen angiotensin I

reninangiotensinogen angiotensin I bradykinin

inactivefragments

angiotensin II

bradykinin

inactivefragments

angiotensin II

vasoconstriction

↓ noradrenalinreuptake

thirst, ADH &ACTH

aldosterone

bradykinin

inactivefragments

Angiotensin Converting Enzyme Inhibitors

CONSENSUS-I

• NYHA class IV

• 40mg enalapril Vs. placebo

• 40% risk reduction of death

• reduced hospitalisation

• less need for duiretics

• Biggest benefit in advanced disease

Angiotensin Converting Enzyme Inhibitors

SOLVD, SAVE, AIRE & TRACE

• mild-moderate symptoms + LVEF < 30%

• various agents

• n = 7105

• 23% risk reduction - death (95%CI 12% - 23%, p=0.001)

• 35% risk reduction - combined death & admission for HF (95%CI 12% - 23%, p=0.001)

Angiotensin II Receptor Antagonists

• ACE inhibitors prevent breakdown of bradykinin, which causes cough in 10%

• Moderate quality evidence to show angiotensin II blockers are as effective as ACEi.

AIIRB Vs Placebo

• 22 RCT - meta-analysis

• NYHA class I - IV

• n = 38,080

• follow up 2.7 years

• Odds Ratio on all cause mortality = 0.83 (95%CI 0.69 - 1.00)

AIIRB Vs Placebo

• n = 38,080

AIIRB Vs ACEi

• n = 5,201

Beta Blockers

CIBIS-II

• NYHA class III - IV, LVEF < 35%

• adjuvant to ACEi

• n = 2,600

• Risk Reduction all cause mortality = 34% (p < 0.0001)

Beta Blockers

CIBIS-II

• NYHA class III - IV, LVEF < 35%

• n = 2,600

• Risk Reduction all cause mortality = 34% (p < 0.0001)

MERIT-HF

• NYHA class I - II

• n = 3,988

• similar mortality benefit

Beta Blockers - Meta-analysis

Mild to Moderate

• n = 10,315

• Death 8% Vs 13%

• OR 0.64 (CI 0.53 - 0.79)

Mild to Moderate

• n = 10,315

• Death 8% Vs 13%

• OR 0.64 (CI 0.53 - 0.79)

Severe

• NYHA class IV

• adjuvant to ACEi + duiretics

• n = 635

• Death 18% Vs 25%

• RR 0.71 (CI 0.52 - 0.96)

Aldosterone Receptor Antagonists

1 RCT - Spironolactone

• NYHA class III - IV

• adjuvant to ACEi + βB

• n = 1,663

• 2 year follow up

• Death 35% Vs 46%

• ARR 11% (CI 7% - 16%)

• RR 0.75 (CI 0.66 - 0.85)

• Risk of hyperkalaemia with ACEi

• Gynaecomastia / breast pain 10%

• Eplerenone

1 RCT - Spironolactone

• NYHA class III - IV

• adjuvant to ACEi + βB

• n = 1,663

• 2 year follow up

• Death 35% Vs 46%

• ARR 11% (CI 7% - 16%)

• RR 0.75 (CI 0.66 - 0.85)

Cardiac Glycosides

• Digoxin inhibits Na/K ATPase

• Intracellular Ca↑

• ↑ delivery of Na to distal tubule

• ↑ vagal tone

Cardiac Glycosides

• ↑ vagal tone

Cardiac Glycosides

• ↑ vagal tone

• Toxicity

• renal failure (try digitoxin)

• hypothyroidism

• elderly

• duiretics

Digoxin

Meta-analysis

• sinus rhythm

• n = 7,896

• Follow up 36 months

• Death - no difference

• Hospitalisation OR 0.68 (CI 0.61 - 0.75)

Drugs to be avoided

• Inotropes

• Calcium channel blockers

• Class 1 antiarythmics

Sudden Cardiac Death

Sudden Cardiac Death accounts for 50% of patients with an impaired left ventricular ejection fraction.

Adapted from MERIT-HF Study Group. Lancet 1999;353:2001–7.

• Amiodarone

• Implantable Cardioverter-Defibrillator (ICD)

Implantable Cardioverter-Defibrillator (ICD)

• QRS criteria

• LVEF criteria

ICD Randomised Controlled Trials

Cohorts n Criteria QRS LVEF

MADIT II ICD v. med 1232 post MI < 30%

COMPANION CRT v. CRT-D v. Med 1520 > 120ms < 35%

DEFINITE ICD v. Med 458 non IHDevidence of arrhythmia

SCD-HeFTICD v. Med

v. ICD + amiodarone2521 non IHD < 35%

ICD Pooled Results

• Irrespective of QRS

• Ischaemic & non ischaemic heart failure

ICD Pooled Results

• Irrespective of QRS

• Ischaemic & non ischaemic heart failure

Relative Risk 0.74

95% CI 0.67 - 0.83

p 0.00001

Absolute Risk Reduction

NNT 13

Treatment OptionsAcute Decompensated Heart Failure

Summary of Benefit

Symptoms Mortality SCD

Duiretics ↓↓↓ ↔ ↔

ACE inhibitors ↓↓ ↓↓ (↓)

Angiotensin II antagonists ↓↓ ↓↓ ↔

Beta blockers ↓ ↓ ↓↓

Glycosides ↓ ↔ ↔

Aldosterone antagonists ↓ ↓ ↔

ICD (primary prevention)

?↑ ↓↓ ↓↓↓

Relative Impact On Survival

RR NNT

ICD (primary prevention) 7.9% 13

ACE inhibitor /Angiotensin II receptor antagonist 6.1% 16

Beta blockers 4.4% 23

Aldosterone antagonists(severe disease & in addition to ACEi & βB)

Alternative Strategy

• Fluid resuscitation

• Antibiotics

Questions

Key Points

• ACE inhibitors/ Angiotensin II receptor antagonists and Beta Blockers are proven to slow progression through NYHA grades and increase survival.

• Aldosterone antagonists confer worthwhile additional benefitCAUTION: Hyperkalaemia.

• Digoxin might keep you out of hospital but doesn’t make you live longer

• ICD for anyone with an ejection fraction < 35%

• No evidence for any treatment in diastolic heart failure

• Inotropes (except digoxin), Ca channel blockers and Class I anti-arrhythmic increase mortality in chronic heart failure

Heart Failure Treatments · 2019. 11. 18. · • Biggest beneﬁt in advanced disease Thursday, 10...

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