congestive heart failure dr ian coombes adopted from duncan mcrobbie principal clinical pharmacist...

Congestive Heart Failure

Dr Ian CoombesAdopted from Duncan McRobbie

Principal Clinical Pharmacist (with permission)

Signs and Symptoms

• fatigue• exertional dyspnoea• orthopnoea• PND• cardiomegaly• pitting oedema• crackles • raised JVP

• NYHA I - no limitation of physical activity

• NYHA II- slight limitation

• NYHA III - marked limitation

• NYHA IV - inability to carry out physical activity

NYHA Classification

• acute MI• hypertension• toxins (alcohol, cytotoxics)• viruses/bacteria• valve disease• cardiomyopathies

Causes

Prevalence

• 1-2% population• 3-5% of those >65 years of age• 10% of those >80 years• 50% patients die within 2 years of diagnosis• 65% of patients with severe CHF die within 1 yr

Survival After Initial Diagnosis of HF

100%

50%

0%3 months 18 months

Hospitalisations

74,500 hospital admissions in 2000/2001Length of stay > 13 days (3x average LOS)1,000,000 in-patient daysAdmission rates projected to increase by >50% over the

next 25 yearsReadmission rates as high as 50% over 3 months

Readmission - causesCauses of Readmission Frequency (%)

Arrythmias 8-28Infections 16-23Poor compliance 15-32Angina 14-33Iatrogenic factors 10Inadequate drug therapy 17Inadequate discharge/follow up 35Failed social support system 21

Erhardt and Cline 1998 (Lancet)

Over 50% preventable

Signs and Symptoms

Symptoms Signs Investigations

SOA Tachycardia Chest X-raySOBOE Increased JVP EchocardiogramFatigue Oedema Ambulatory ECGOrthopnoea Rales Exercise treadmillPND (Paroxysmal nocturnal dyspnoea)

Hepatomegaly Cardiac catheter

Nocturia AscitesAnorexia CardiomegalyWeight loss

Classifying Heart Failure – the New York Heart Association method

• NYHA I No symptoms with ordinary physical activity (walking and climbing stairs)

• NYHA II (mild)Slight limitation of activity with dyspnoea on moderate to severe activity (climbing stairs or walking uphill)

• NYHA III (moderate)Marked limitation of activity. Less than ordinary activity causes dyspnoea (restricting walking distance and limiting climbing to one flight of stairs)

• NYHA IV (severe)Severe disability, dyspnoea at rest (unable to carry out physical activity without discomfort)

Rules of HF

Remember

CO=SVxHRBP=TPRxCO

Remembersymptoms haemodynamics symptoms survival

Remember

Starling’s Law: preload = force of contractionLapace’s Law: large heart = inefficient

cardiac output

cardiac workload

afterload

arterio-constriction

nor-epinephrine

aorticblood flow

SNS

Neurohormonal model of Heart Failure – Sympathetic Response

RememberCO = SV x HR

cardiac output

cardiac workload

Renal blood flow

RAS

angiotensin

aldosterone

Na+ and H2O retention

preloadafterload

arterio-constriction

remodelling

veno-constriction

Neurohormonal model of Heart Failure – renin-angiotensin-aldosterone

RememberStarlings

Law

cardiac output

cardiac workload

Renal blood flow

RAS

angiotensin

naturetic peptides

aldosterone

Na+ and H2O retention

preloadafterload

arterio-constriction

nor-epinephrine

aorticblood flow

SNS

veno-constriction

B-blockers

ACE-I

NEP-I

spironolactone

diuretics

nitrates

hydralazine

digoxin

Treatment of Heart Failure Remember

Survival = drug treatment

• loops most effective • symptomatic relief• Na+ retention• H2O loss• preload ( ventricle

filling pressure)• afterload (arterial

dilatation)

Side effects• dehydration• hypotension• hypokalaemia• hypomagnesaemia• hypouricaemia and

gout• non-compliance

issues

Role of Diuretics

Role of ACE-inhibitors

• improves mortality (CONSENSUS)

• better than vasodilator therapy (VeHFT I and II)

• large well conducted trials

• preload (inhibits effect)

• afterload (inhibits vasoconstriction)

Side effects• hypotension (6%)

• hyperkalaemia (6%)

• cough (40%)

• dizziness (50%)

• raised serum creatinine (0.2%)

Circulating Renin-Angiotensin System

angiotensinogen

renin

Ang I Ang IIACE

AT1/AT2 receptors

ACE

Ang (1-5)

angiotensinogen

renin

Ang I

Ang II

ACE

AT1 AT2 ATx

Ang (1-7)NEP

Potential Role of Angiotensin (1-7)

pressortrophic

antinatriuretic

depressorantitrophicnatriuretic

depressorantitrophicnatriuretic

angiotensinogen

renin

Ang I

Ang II

ACE

AT1 AT2 ATx

Ang (1-7)NEP

ACE

Ang (1-5)+

–

pressortrophic

antinatriuretic

depressorantitrophicnatriuretic

depressorantitrophicnatriuretic

ACEinhibitor

ACEinhibitor

Potential Role of Angiotensin (1-7)

icatibant

bradykinin

Ang II

Renin-Angiotensin/Kallikrein-Kinin Systemskininogen

kallikrein

inactive peptides

kininase II

angiotensinogen

renin

Ang I

ACE

B2 AT1 AT2

pressortrophic

antinatriuretic

depressorantitrophicnatriuretic

depressorantitrophic

cardioprotectiveNO

+

–

ACEinhibitor

B2 receptorknock-out

Landmark trials with ACE inhibitors in HF

Trial n EF% Drug Death Hospitalisation Follow up NNT(death)

CONSENSUS1987

253 <35%(IV)

enalapril 36 vs 50 reduced 1 year 6

SOLVD-P1992

4228 <35(I)

enalapril trend toreduction

reduced 4 years 104

SOLVD – T1991

2500 < 40(II-III)

enalapril 12.3 vs 15.5 reduced 3 years 31

ATLAS1997

3164 <35(II-IV)

lisinopril no difference reduced 4 years -

Role of ARBs

• improves mortality (ELITE I and II / CHARM)

• added into conventional therapy (ValHeft / CHARM)

• Less s/es

Role of Beta blockers

• improves mortality (CIBIS 2)

• added into conventional therapy

• attenuates sympathetic drive (outweighs -ve ionotropic effect)

• not all beta-blockers are equivalent (bisoprolol and carvedilol best supported by evidence)

Side effects• hypotension • bradycardia• peripheral

vasoconstriction• impotence• bronchospasm

Role of vasodilator therapy

• preload (venodilators - nitrates)

• afterload (arterial dilators - prazosin)

• large trials show good benefit but lots of side effects

Side effects• hypotension• headache• tachycardia• SLE (hydralazine)

Role of Digoxin

• used in initial trials• myocardial

contractility • lost favour because of

toxicity• renally cleared -

dependent on age, weight & RF

Side effects• anorexia• N,V,D• abdominal pain• visual disturbances• drowsiness• arrythmias• heart block

Role of spironolactone

• improves mortality (RALES)

• added into conventional therapy

• attenuates aldosterone effect

• only small doses required

Side effects• hyperkalaemia• gi disturbances• impotence• gynocomastia• rash

Adjunct Therapy• Digoxin in SRDigoxin in SR

– DIG trial DIG trial : no mortality benefit but reduction in : no mortality benefit but reduction in hospitalisations and improved symptomshospitalisations and improved symptoms

– useful in symptomatic patients where other drug useful in symptomatic patients where other drug therapy is optimisedtherapy is optimised

– should not be withdrawn from pts with HFshould not be withdrawn from pts with HF

• AnticoagulationAnticoagulation– if prolonged bed rest : prophylactic heparinif prolonged bed rest : prophylactic heparin– if LV dilatation / thrombus : chronic warfarin therapyif LV dilatation / thrombus : chronic warfarin therapy

Mortality remains high

• ACEi Risk reduction 35% (mortality and hospitalizations)

Blockers Risk reduction 38% (mortality and hospitalizations)

• Oral nitrates and hydralazineBenefit vs. placebo; inferior to enalapril (mortality)

Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498

However: 4-year mortality remains ~40%

Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498

Role of other treatments

• ?? Ca++ channel antagonists - -ve ionotropic, amlodipine appears safe

• ?? other antiarrythmics -

• dobutamine - increases CO, but palliative

• Levosimendan- severe CHF

• naturetic peptide inhibitors / recombinant naturetic peptides- omapatrilat / neseritide

• Biventricular pacing - severe CHF high cost

• transplantation - 85% survival @ 5yrs

Congestive cardiac failurePharmaceutical Care Plan

Need for Drug : Diagnosis of CHF

Selection of Specific Drug: Symptom control - diuretics

Decrease mortality; ACE, B-blockers

Co-modibdity: anticoagulation

Patient factors

Selection of Regimen: Loading doses, maintenance dose

Drug factors

Provision of Drug: Timely, accurate

Administration of Drug: Timing, food

Monitor Effectiveness: Symptoms, pulse,cholesterol, side effects

Counsel / Educate: Expected effects, side effects

Risks vs benefits

Evaluate Effectiveness: Beneficial effects > detrimental effects??