Post on 22-Dec-2015
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
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%)
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??