slide1 l.
Download
Skip this Video
Download Presentation
Medication Therapy Management of the Patient with Congestive Heart Failure November 5, 2007 Joe Anderson, PharmD, PhC, B

Loading in 2 Seconds...

play fullscreen
1 / 104

Medication Therapy Management of the Patient with Congestive Heart Failure November 5, 2007 Joe Anderson, PharmD, PhC, B - PowerPoint PPT Presentation


  • 172 Views
  • Uploaded on

Medication Therapy Management of the Patient with Congestive Heart Failure November 5, 2007 Joe Anderson, PharmD, PhC, BCPS Office: 272-3664 Email: janderson@salud.unm.edu College of Pharmacy University of New Mexico Health Sciences Center. Learning Objectives.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Medication Therapy Management of the Patient with Congestive Heart Failure November 5, 2007 Joe Anderson, PharmD, PhC, B' - ami


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Medication Therapy Management of the Patient

with Congestive Heart Failure

November 5, 2007

Joe Anderson, PharmD, PhC, BCPS

Office: 272-3664

Email: janderson@salud.unm.edu

College of Pharmacy

University of New Mexico Health Sciences Center

learning objectives
Learning Objectives
  • List and understand the current guidelines for the management of chronic heart failure.
  • Assess the appropriateness of drug therapy for a patient with chronic heart failure.
  • Identify precipitating factors in heart failure, particularly drugs that may precipitate or exacerbate heart failure.
  • For a given patient with heart failure, recommend an appropriate pharmacotherapeutic plan.
  • Provide proper patient education regarding lifestyle modification for the patient with chronic heart failure.
reading
Reading:
  • Hunt SA, Abraham WT, Chin MH. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). Circulation 2005;112:1-27.
  • Adams KF, Lindenfield J, Arnold JMO, et al. Executive Summary: HFSA 2006 Comprehensive Heart Failure Guideline. J Cardiac Failure 2006;12:10-38.
definitions
Definitions
  • Heart failure: a syndrome that exists when the heart is unable to pump sufficient blood to meet the metabolic needs of the body
    • Characterized by elevated cardiac filling pressures (preload) and or inadequate oxygen delivery, at rest or during stress, caused by cardiac dysfunction
definitions systolic dysfunction
Definitions: Systolic Dysfunction

Systolic Dysfunction

  • an impairment of the contraction of left ventricle such that stoke volume (SV) is reduced for any given end-diastolic volume (EDV) or filling pressure.
    • Ejection fraction is reduced (< 45%)

Left ventricular ejection fraction

  • SV/EDV
  • Normal: 50 - 70%
  • Objective measure of systolic function
  • Measured by
    • ECHO (Echocardiogram)
    • RNV (Radionuclide ventriculogram)
    • cardiac catheterization
definitions diastolic dysfunction
Definitions: Diastolic Dysfunction
  • New Name: Heart failure with preserved left ventricular systolic function (or EF)
  • Ventricular filling rate (increased HR) and the extent of filling are reduced (decreased EDV) or a normal extent of filling is associated with an inappropriate rise in ventricular diastolic pressure. Normal EF is maintained.
hf in the us current statistics
HF in the US: Current Statistics
  • Prevalence: 4.9 million symptomatic patients
  • Incidence: ~550,000 new cases/year
    • 1% between the ages of 50 and 59 years; >10% over age 80
  • 999,000 hospital discharges
  • Mortality: >51,000 deaths/year
  • Prevalence of HF in US is increasing

American Heart Association. 2002Heart and Stroke Statistical Update. 2001.

American Heart Association. Heart Disease and Stroke Statistics —2003 Update. Dallas, Tex: American Heart Association; 2002.

hf prevalence projections

12

10

10

8

6

4.7

3.5

4

2

0

1991

2000

2037*

HF Prevalence Projections

Heart Failure Patients in US

(millions)

*Rich M. J Am Geriatric Soc. 1997;45:968–974.

American Heart Association. 2002Heart and Stroke Statistical Update. 2001.

American Heart Association. Heart Disease and Stroke Statistics —2003 Update. Dallas, Tex: American Heart Association; 2002.

causes of heart failure systolic dysfunction
Causes of Heart FailureSystolic Dysfunction

Dilated Cardiomyopathy

  • Ischemic disease
    • myocardial ischemia
    • myocardial infarction
  • Non-ischemic disease
    • Primary myocardial muscle dysfunction
    • valvular abnormalities
    • hypertension
    • structural damage and/or damage to myocardial walls
neurohormonal mechanism of chf
Neurohormonal Mechanism of CHF
  • Components
    • Endothelin
    • Vasopressin (ADH)
    • Atrial Natriuretic Peptide
    • Endothelium-Derived Relaxing Factor
    • RAAS
    • SNS
neurohormonal mechanism of chf13
Neurohormonal Mechanism of CHF
  • Direct toxic effects of NE and AII
    • Arrhythmias
    • Apoptosis
  • Impaired diastolic filling
  • Increased myocardial energy demand
  • Increased pre- and afterload
  • Platelet aggregation
  • Desensitization to catecholamines
slide14

Decrease Cardiac Output

  • Renal Perfusion
  • SNS Activity
  • Renin
  • Contractility
  • HR
  • Angio I

Angiotensinogen

ACE

Vasoconstriction

  • Angio II
  • Endothelin
  • Aldosterone

Na+ / H2O

Ventricular

  • SVR

retention

dilation

(afterload)

  • LVEDV

(preload)

Atrial Distention

Ventricular

  • Proinflammatory Cytokines (TNF, IL-6)

hypertrophy

ANP

AVP

pathologic progression of cv disease
Pathologic Progression of CV Disease

Coronary artery disease

Arrhythmia

Left ventricularinjury

Hypertension

Low ejectionfraction

Pathologicremodeling

Death

Diabetes

Cardiomyopathy

Pump failure

Valvular disease

Symptoms:DyspneaFatigueEdema

Chronicheartfailure

  • Neurohormonalstimulation
  • Endothelial dysfunction
  • Myocardial toxicity
  • Vasoconstriction
  • Renal sodium retention

Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.

pathophysiology
Pathophysiology

LV function

LV impedence

(afterload) Cardiac output

+

Salt/water retention

(preload)

Neurohormonal

activation

The Vicious Cycle of Heart Failure

slide18

New York Heart Association

Functional Classification

I. No limitations of physical activity, no symptoms with ordinary activities

II. Mild/slight limitation, symptoms with ordinary activities

III. Moderate/marked limitation, symptoms with less than ordinary activities

IV. Severe limitation, symptoms of heart failure at rest

Symptoms: Dyspnea or fatigue

Adapted from Criteria Committee of the New York Heart Association, 1994.

4 steps for pharmacists to decrease chf mortality and morbidity
4 Steps for pharmacists to decrease CHF mortality and morbidity

1

  • Identify patients with heart failure and assess functional status
  • Educate and encourage lifestyle modification
  • Recommend optimal pharmacotherapy
  • Follow-up

2

3

4

Source: Joe Anderson’s logical thinking

4 steps for pharmacists to decrease chf mortality and morbidity20
4 Steps for pharmacists to decrease CHF mortality and morbidity
  • Recent study documented benefits of a RPh to improve medication adherence in CHF patients
    • Patients randomized to interventional RPh or usual care
    • Interventional RPh provided additional education about CHF and medications
    • At 9 months adherence was 78.8% vs. 67.9%, which dissipated 3 months after completion of study
    • ER visits and Hospitalizations were decreased by 19% and annual direct healthcare costs were decreased by $2,960.00 per patient.

Ann Intern Med. 2007;146:714-725.

pharmacist clinician evidence of benefit
Pharmacist Clinician: Evidence of Benefit
  • UNMH Congestive Heart Failure Clinic
    • Multi-disciplinary clinic (cardiologists, pharmacist clinicians, clinical nurse specialist, nurse case-manager)
    • PhC duties: interview patients, provide patient education, perform physical assessment, review laboratory and other diagnostic data, and formulate assessment and therapeutic plan
pharmacist clinician evidence of benefit22
Pharmacist Clinician: Evidence of Benefit
  • Initial outcomes assessment of HFC performed in 2000
  • First 35 patients enrolled in clinic
  • Patient outcomes compared from 1 yr prior to enrollment in HFC to 1 yr after enrollment
  • Outcomes:
    • Hospital admissions for heart failure
    • Patient functional class
    • Optimization of medication regimens
    • Health care costs
pharmacist clinician evidence of benefit23
Pharmacist Clinician: Evidence of Benefit
  • Outcomes study results:
    • 91% reduction in CHF hospitalizations
    • Significant improvement in:
      • Patient’s level of functioning
      • Utilization of heart failure medications proven to reduce morbidity and mortality
    • Overall cost savings of $161,856/year or $4624/patient

O’Connell AM et al. Am Heart J 2001;254-258.

pharmacist clinician evidence of benefit24
Pharmacist Clinician: Evidence of Benefit

ACE inhibitor/ARB and Beta-blocker utilization

Leos C, et al. Presented at 2005 Western States Residents Conference, Monterrey, CA

pharmacist clinician evidence of benefit25
Pharmacist Clinician: Evidence of Benefit
  • PMG PhC CHF Program
  • Savings Due to Decreased Admits
    • Cost savings from 1/1/2003 through 6/30/2003: $383,278.77
  • Savings Due To Decreased ER Visits
    • Cost Savings from 1/1/2003 through 6/30/2003: $13,770
step 1 identifying the patient with heart failure
Step 1: Identifying the patient with heart failure
  • Identify patients receiving concomitant digoxin and furosemide or other loop diuretics.
  • Ask either the patient, their spouse or their caregiver.

“Has your Dr told you that you have heart failure or a weakened heart or that your heart doesn’t pump as well as it use to?”

slide27

Step 1: Assess functional status

Do you get winded or have trouble catching your breathwhen climbing a flight of stairs?

Do you get winded when walking around your house orthe store?

Do you ever get awakened at night by the sudden inabilityto catch your breath?

Do you need to sleep with extra pillows in order to sleepcomfortably?

Do you now sleep in a chair instead of sleeping in bed?

Have you experienced any recent weight gain?

step 2 educate about lifestyle modification
Step 2: Educate about Lifestyle modification
  • Make sure all your patients have a scale
  • Instruct patient to weigh and record first thing every morning after voiding
  • Patient should call their provider if weight increases by 2 lbs/day or 5 lbs/week.
slide29

Step 2: Educate about Lifestyle modification

  • Teach to “shake” the salt habit
  • No more than 2000 mg NaCl.
    • One level teaspoon has approximately 2000 mg.
    • Therefore no added salt to foods is best.
    • Enough sodium (salt) can be obtained from one’s diet without adding any table salt.
    • Careful with salt substitutes and potassium sparing meds!!
slide30

Step 2: Educate about Lifestyle modification

  • Emphasize the importance of exercise for improvement of symptoms and quality of life.
  • Encourage patient to consult physician about the appropriate type and amount of exercise.
slide31

Step 2: Educate about Lifestyle modification

  • Encourage weight loss, if overweight.
  • Smoking cessation

Benefits include:

    • Decrease BP
    • Helps with exercise tolerance
    • Decreases risk of blood clots
  • Avoid alcohol
    • Moderate intake may be O.K.
slide32

Step 3: Recommend optimal pharmacotherapy

Like most veterinary students, Doreen breezes through chapter 9.

acc aha guidelines
ACC/AHA Guidelines
  • Class I: Conditions for which there is evidence and/or general agreement that a given procedure/therapy is useful and effective.
  • Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of performing the procedure/therapy.
    • Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.
    • Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

acc aha guidelines34
ACC/AHA Guidelines
  • Class III: Conditions for which there is evidence and/or general agreement that a procedure/therapy is not useful/effective and in some cases may be harmful.
  • The levels of evidence upon which these recommendations are based were ranked as
    • Level A if the data were derived from multiple randomized clinical trials
    • Level B when data were derived from a single randomized trial or nonrandomized studies
    • Level C when the consensus opinion of experts was the primary source of recommendation.

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

slide35

Ex. Pts with:

previous MI, LV systolic dysfunction, asymptomatic valvular disease

Ex. Pts with:

HTN, CAD, DM, obesity, metabolic Sx, exposure to cardiotoxins, or a family history

Ex. Pts with:

known stuctural disease & SOB, fatigue, reduced exercise tolerance

Pts with marked Sxs at rest despite maximal medical tx, recurrent hospitalizations

Stage A

High risk for HF but no Sx’s or stuctural heart disease

Stage B

Stuctural heart disease but no Sx’s of HF

Stage C

Stuctural heart disease with prior or current Sx’s of HF

Stage D

Refractory HF requiring specialized interventions

Therapy

-All in Stage A & B

-Drugs for routine use:

Diuretics (if  fluid)

ACEIs

BBs

-Dietary sodium restriction

Selected Patients:

ARBs, aldosterone antagonist, digoxin, hyd/ntg

Devices (BiV pacing, ICD)

Therapy

-All in Stage A, B, & C

-Mechanical assist devices

-Heart transplantation

-Continuous IV inotropic infusions

-Hospice care

Therapy

-All in Stage A

-ACEI/ARB for appropriate pts

-BB’s for appropriate pts

Therapy

-Tx HTN

-Smoking cessation

-Tx lipids

-Regular exercise

-d/c ETOH

-d/c illicit drugs

-ACEI’s/ARB for high risk pts

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

slide36

ACC/AHA Guidelines: Diuretics

  • No data regarding morbidity or mortality
  • Class I: Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention. (Level of Evidence: C)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

pharmacotherapy diuretics
Pharmacotherapy: Diuretics
  • Decrease Preload
  • Thiazides can be used if GFR>30ml/min
    • Work on distal tubule
  • Loop diuretics
    • Ascending loop of henle
    • Dosed once or twice daily
  • Resistance: Use combination therapy
  • Monitor K+ , Mg2+, BUN, and SCr
pharmacotherapy diuretics38
Pharmacotherapy: Diuretics
  • Keep K+ between 4.0 to 5.0 meq/L
  • Supplement Mg2+ if < 1.6 meq/L
  • Back down dose if hypotensive or evidence of azotemia (BUN/CR > 20)
diuretic resistance
Diuretic Resistance

Proximal Tubule

Distal Tubule

NaHCO3

Thiazides

X

Collecting tubule

X

Ca2+

Spironolactone

X

Acetazolamide

X

NaCl

Na+

(Aldosterone)

Mg2+

K+

2CL-

Loop Diuretics

H2O

(ADH)

K+

H+

Loop of Henle

digoxin
Digoxin
  • (+) inotrope, decreases ventricular rate, possibly some NH modulation
  • Monitor serum levels if toxicity or noncompliance suspected, or if renal function or interacting drugs added
digoxin41
Digoxin
  • DIG trial (N Engl J Med 1997:336:525-33)
    • No survival benefit versus placebo
    •  CV and CHF hospitalizations by 8% and 23%, respectively (p<0.001) ACC/AHA Recommendation
  • Class IIa: Digitalis can be beneficial in patients with current or prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF. (Level of Evidence: B)

“…digitalis does not compare favorably with such agents as the aldosterone blockers…The Writing Committee, therefore, decided to change the level of recommendation for digitalis glycosides from Class I to Class IIa…”

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

digoxin42
Digoxin
  • Low dose sufficient 0.125 mg/d
  • Inotropic effects seen at low concentrations (0.5 – 0.8 ng/mL) (NEJM 2002; 347:1403-11)
  • Women may not derive benefit

“The conflicting data regarding the efficacy of digoxin in women suggests that if it is prescribed, particular attention should be paid to dosing and renal function.”

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

J Am Coll Cardiol 2005;46:497-504.

raa system during ace inhibition
RAA System - During ACE Inhibition

Angiotensinogen

Renin

Inactive Compounds

t-PA Cathepsin G

Angiotensin I

Chymase CAGE

ACE

Angiotensin II

Bradykinin

AT2 receptor

AT1 receptor

Bradykinin2 receptor

VasodilationInhibition of Vascular and Myocardial Hypertrophy

VasoconstrictionCell GrowthSodium and Fluid Retention Sympathetic Activation

VasodilationImproved Endothelial FunctionAntiproliferative Effect

effect of ace inhibitors on mortality reduction in patients with heart failure
Effect of ACE Inhibitors on Mortality Reduction in Patients With Heart Failure

Mortality

Trial

ACEI

Controls

RR (95% CI)

Chronic CHF

CONSENSUS I

39%

54%

0.56 (0.34–0.91)

SOLVD (Treatment)

35%

40%

0.82 (0.70–0.97)

SOLVD (Prevention)

15%

16%

0.92 (0.79–1.08)

Post MI

SAVE

20%

25%

0.81 (0.68–0.97)

AIRE

17%

23%

0.73 (0.60–0.89)

TRACE

35%

42%

0.78 (0.67–0.91)

SMILE

5%

6.5%

0.75 (0.40–1.11)

Average

21%

25%

acei dosing
ACEI: Dosing

Drug Initial Dose Target Dose

Enalapril* 2.5 mg BID 10 mg BID

Captopril* 6.25-12.5 mg TID 50 mg TID

Lisinopril* 5 mg QD 20 mg QD

Quinapril 5 mg BID 20 mg BID

Ramipril* 1.25-2.5 mg BID 5 mg BID

Fosinopril 5-10 mg QD 20 mg QD

*Clinical trial evidence of decreased CHF morbididty/mortality

high dose ace inhibitor treatment
High dose ACE-inhibitor treatment
  • ATLAS study compared “high” and “low” dose lisinopril for effects on mortality.
    • No difference in mortality.
    • High-dose reduced hospitalizations for any cause (-13%) and for heart failure (-24%); p<0.05.

Packer M, et al. Circulation 1999;100:2312.

acc aha guidelines ace inhibitors
ACC/AHA Guidelines: ACE inhibitors

Class I: ACE Inhibitors are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. (Level of Evidence: A)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

ace i in chf precautions
ACE-I in CHF: Precautions
  • Renal Impairment
  • Hyperkalemia
  • Hypotension
  • Cough *Patients should be seen in 1 – 2 weeks to monitor their serum Cr, K+, and B.P.
step 3 recommend optimal pharmacotherapy
Step 3: Recommend optimal pharmacotherapy
  • ACE Inhibitors for all patients
    • Initial dose 1/2 usual: SBP < 100 mmHg, SCr > 2.0 mg/dL, Na < 130 mg/dL
    • Try to achieve target dose but not at the expense of beta-blocker therapy
    • ASA may interfere with efficacy, recommend low-dose ASA (< 160 mg) if necessary
    • Recommend f/u in 1 - 2 weeks to check BP, BUN/SCr, and K+.
patients with crd and htn have minimal changes in serum creatinine with acei or arb therapy
Patients With CRD and HTN Have Minimal Changes in Serum Creatinine With ACEI or ARB Therapy

2.9

2.7

2.5

2.3

2.1

1.9

1.7

1.5

1.3

1.1

0.9

0.7

A

ACEI or ARBStarted

B

Serum Creatinine (mg/dL)

C

Baseline

1

2

3

4

Weeks

Bakris GL, Weir M. Arch Intern Med. 2000;160(5):685-693.

Reprinted by permission, American Medical Association.

ace intolerant patients
ACE-intolerant patients
  • The frequency of cough is approximately 5% to 10% in white patients of European descent and rises to nearly 50% in Chinese patients
  • Angioedema occurs in < 1%, more in African-Americans
  • A significant increase in serum creatinine (> 0.3 mg per dL) is observed in 15% to 30% of patients with severe HF, but in only 5% to 15% of patients with mild to moderate symptoms
    • May be managed by decreasing diuretic dose
raa system during arb therapy
RAA System - During ARB Therapy

Angiotensinogen

Renin

Inactive Compounds

t-PA Cathepsin G

Angiotensin I

Chymase CAGE

ACE

Angiotensin II

Bradykinin

AT2 receptor

AT1 receptor

Bradykinin2 receptor

VasodilationInhibition of Vascular and Myocardial Hypertrophy

VasoconstrictionCell GrowthSodium and Fluid Retention Sympathetic Activation

VasodilationImproved Endothelial FunctionAntiproliferative Effect

alternatives for acei intolerant patients

Mortality

Mortality

Mortality

Mortality

CV mort +

CHF Hosp.

Mortality

Mortality

Alternatives for ACEI-intolerant patients

Trial

Treatment

10 Endpoint

Result

Chronic CHF

VHeFT I

 34% ISDN/HYD; p<0.05

ISDN/HYD vs PBO

VHeFT II

ISDN/HYD vs Enalapril

 11% ACEI; p=0.08

ELITE II

Losartan vs captopril

 13% ACEI; p=0.16

Val-HeFT (subgrp)

Valsartan vs PBO

 33% ARB; p<0.0017

CHARM-Alter.

Candesartan vs PBO

 30% ARB; <0.0001

Post MI

OPTIMAAL

Losartan vs captopril

 13% ACEI; p=0.069

VALIANT

Valsartan vs captopril

 2% ACEI; NS

VHeFT I N Engl J Med 1986;314:1547-52. VHeFT II N Engl J Med 1991;325:303-10. ELITE II Lancet 2000;355:1582-7. Val-HeFT (subgroup) J Am Coll Cardiol 2002;40:1414-21. CHARM-Alternative Lancet 2002;360:752-60. OPTIMAAL Lancet 2002;360;752-60. VALIANT N Engl J Med 2003;349:1893-1906.

acc aha guidelines ace inhibitor intolerant patients
ACC/AHA Guidelines: ACE inhibitor intolerant patients
  • Class I
    • Angiotensin II receptor blockers approved for the treatment of HF (e.g. candesartan, valsartan) are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACEI intolerant (Level of Evidence: A)
  • Class IIb
    • A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency (Level of Evidence: C)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

rationale for beta blockers

1.0

0.8

0.6

PNE < 400 pg/ml

0.4

0.2

PNE 400-800 pg/ml

PNE > 800 pg/ml

0

0 10 20 30 40 50 60

Time (months)

PNE = Plasma norepinephrine

Cohn et al. N Engl J Med 1984;311:819-23

Rationale for Beta-blockers

Probability of survival

effects of chronic adrenergic activation
Effects of chronic adrenergic activation
  • Myocardial remodeling
  • Direct toxic effects of NE
    • Apoptosis
  • Arrhythmias
  • Impaired diastolic filling
  • Increased myocardial energy demand
  • Increased pre- and afterload
  • Desensitization to catecholamines
which beta blocker
Which Beta-blocker?
  • Bisoprolol, Metoprolol CR/XL, and Carvedilol have all shown mortality benefits
    • All are lipophilic
    • All are without ISA
  • Non-selective vs Selective Beta-blockade
    • COMET Trial: 3029 patients, class II-IV
    • Carvedilol (25mg BID) vs Metoprolol tartrate (50mg BID)
comet study primary endpoints
COMET Study: Primary endpoints

Primary

endpoints

Hazard

Ratio

Carvedilol

Metoprolol

95% CI

P

Mortality

512/1511

33.9%

600/1518

39.5%

0.83

0.74- 0.93

0.0017

Annual mortality

8.3

10.0

Mortality or

all cause hosp.

1116/1511

73.9%

1160/1518

76.4%

0.94

0.86-1.02

0.122

Lancet 2003;362:7-13.

acc aha hf guidelines beta blockers
ACC/AHA HF Guidelines: Beta-blockers

Class I: Beta blockers (using 1 of the 3 proven to reduce mortality, i.e. bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. (Level of Evidence: A)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

slide62

Beta-blocker : Contraindications

  • Documented allergy
  • Reactive airway disease
  • Symptomatic bradycardia or > 1st degree heart block unless has pacemaker
  • Evidence of fluid overload or recent requirement for IV inotropic agents

Diabetes, COPD, advanced age are not contraindications!!! Studies have shown that these groups benefit to the same extent if not more from beta-blocker therapy. (JAMA 2002;288:351-7. NEJM 1998;339:489-97. J Am Coll Cardiol 2001;37:1950-6.)

beta blocker dosing
Beta-blocker dosing
  • Bisoprolol
    • 1.25mg QD doubled at bi-weekly intervals to target dose of 10mg QD
  • Carvedilol
    • 3.125mg BID with food, doubled at bi-weekly intervals to target dose of 25mg BID (50mg BID if > 85 kg)
  • Metoprolol succinate extended release
    • 12.5mg QD (Class III-IV), 25mg QD (Class II), doubled at bi-weekly intervals to target dose of 200mg QD
beta blockers treatment recommendations
Beta-blockers: treatment recommendations
  • Optimize volume status
  • Separate dosing of BB and ACE inhibitor
  • Take carvedilol with food
  • Slowly titrate BB dose
  • Instruct patient to monitor weight daily
  • Increase diuretic dose for volume retention
  • Reduce ACE inhibitor dose if hypotensive
aldosterone effects in chf
Hemodynamic Effects

Retention of Na+ and water

Increased plasma fluid volume

Elevated BP

Non-Hemodynamic Effects

Myocardial & vascular fibrosis

Impaired arterial compliance

Baroreceptor dysfunction

Sympathetic activation

Excretion of K+ and Mg++

Elevated ANP

Parasympathetic inhibition

Aldosterone Effects in CHF
slide66

t-PA Cathepsin G

Chymase CAGE

ACE Inhibitors

AT1 Receptor Blockers

Potassium

Corticotropin

ANP(Inhibits)

Aldosterone “Synthesis Escape” DuringACE Inhibitor and ARB Therapy

Angiotensinogen

Renin

Angiotensin I

ACE

Angiotensin II

Aldosterone Release

slide67

1,663 patients with NYHA class III-IV CHF symptoms, LVEF < 35%, class IV symptoms within past 6 months

Spironolactone 25 mg qd vs placebo

6.200 post-MI with LV dysfxn LVEF < 40%, eplerenone 25-50mg qd vs placebo

adverse events in the rales trial
Adverse Events in the RALES Trial

Spironolactone Placebo p

(n = 822) (n = 841)

One or more events 674 667 NS

Gynecomastia 55 8 < 0.001

Breast pain 10 1 0.006

Serious hyperkalemia 14 10 NS

Discontinued for ADE 62 40 NS

Pitt B, et al. N Engl J Med 1999;341(10):709.

slide69

Spironolactone prescription rates before and after RALES publication

Hospitalization rates for hyperkalemia before and after RALES publication

NEJM 2004;351:543-51

acc aha hf guidelines aldosterone antagonists
ACC/AHA HF Guidelines: Aldosterone antagonists

Class I: Addition of an aldosterone antagonist is reasonable in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal K+ (Level of Evidence: B)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

acc aha hf guidelines aldosterone antagonists71
ACC/AHA HF Guidelines: Aldosterone antagonists
  • Only use if:
    • SCr < 2.5 mg/dL in men, 2.0 mg /dL in women
    • K+ < 5.0 mEq/L
    • CLCR > 30 mL/min
  • Initial dose:
    • Spironolactone 12.5 mg/d (max. 25 mg/d)
    • Eplerenone 25 mg/d (max. 50 mg/d)
  • Monitoring:
    • K+ and renal function at 3 days, 1 week, and at least monthly for the first 3 months

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

escape of angiotensin ii despite ace inhibition

100

80

60

40

*

20

*

*

*

*

*

*

*

0

30

20

10

*

0

Placebo

4 h

24 h

1

2

3

4

5

6

Hospital

Months

Escape of Angiotensin II Despite ACE Inhibition

Plasma ACE

(nmoL/mL/min)

*P <.001 vs placebo

Plasma Ang II

(pg/mL)

Biollaz J, et al. J Cardiovasc Pharmacol. 1982;4(6):966-972, with permission from Lippincott Williams & WIlkins.

raa system combination ace inhibitor arb therapy
RAA System - CombinationACE Inhibitor/ARB Therapy

Angiotensinogen

Renin

Inactive Compounds

t-PA Cathepsin G

Angiotensin I

Chymase CAGE

ACE

Angiotensin II

Bradykinin

AT2 receptor

AT1 receptor

Bradykinin2 receptor

VasodilationInhibition of Vascular and Myocardial Hypertrophy

VasoconstrictionCell GrowthSodium and Fluid Retention Sympathetic Activation

VasodilationImproved Endothelial FunctionAntiproliferative Effect

combination acei arb therapy

Trial

Treatment

10 Endpoint

Result

Chronic CHF

Mortality & Morbidity*

Val-HeFT

Valsartan vs PBO (ACEI,Diuretic, Digoxin,BB)

No diff in mortality; Morbidity  13% ARB; p=0.009

CHARM-Added

CV mortality + CHF Hosp.

Candesartan vs PBO (ACEI, Diuretic, Digoxin, BB)

 15% ARB; p=0.01

Post MI

VALIANT

Valsartan vs captopril vs combination

Mortality

No difference b/w 3 groups; More ADEs with ARB/ACEI

Combination ACEI/ARB Therapy

*Morbidity was defined as hospitalization for HF, resuscitated sudden death, IV inotropes, or vasodilator use.

Val-HeFT, N Engl J Med 2001;345:1667-75. CHARM-Added, Lancet 2003;362:767-71. VALIANT, N Engl J Med 2003;349:1893-1906.

val heft subgroup analysis of effect on morbidity and mortality
Val-Heft: Subgroup analysis of effect on morbidity* and mortality

*Combined endpoint: death, hospitalization for HF, resuscitated sudden death, IV inotropes, or vasodilator use.

Variable

No. of Patients

Relative Risk

Combined end point

ACEI (+), BB (-) 3034

ACEI (+), BB (+) 1610

ACEI (-), BB (-) 226

ACEI (-), BB (+) 140

Death

ACEI (+), BB (-) 3034

ACEI (+), BB (+) 1610

ACEI (-), BB (-) 226

ACEI (-), BB (+) 140

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9

Valsartan Better

Placebo Better

(+) = the use of the drug, (-) = nonuse of drug

N Engl J Med 2001;345:1667-75.

slide76

CHARM-Added

Primary Endpoint by Background Therapy

P-value for

treatment

interaction

Candesartan

Placebo

Beta-blocker

Yes

No

223/702

260/574

232/643

251/633

483/1276

274/711

264/561

275/648

263/624

538/1272

0.14

Recommended dose

of ACE inhibitor

Yes

No

0.26

All patients

0.6

0.8

1.0

1.2

Candesartan

better

Placebo

better

HR

HR, hazard ratio.

McMurray JJV et al. Lancet. 2003;362:767-771.

acc aha guidelines ace inhibitor arb
ACC/AHA Guidelines: ACE Inhibitor + ARB
  • Class IIb
    • The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy. (Level of Evidence: B)
  • Class III
    • Routine combined use of ACEI, ARB, & aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: C)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

nitrates and hydralazine
Nitrates and Hydralazine
  • African-American Heart Failure Trial (A-HeFT)
  • Randomized, placebo-controlled, double-blind trial in 1,050 AA patients with HF (NYHA III/IV & EF < 45%) on standard therapy (ACEI & BB)
    • Placebo or 37.5 mg hydralazine & 20 mg ISDN three times daily, dose doubled if tolerated
    • Primary EP: composite score of weighted values for death from any cause, a first hospitalization for HF during 18-month follow-up period, and change in the QoL at 6 months
    • Secondary EP: Individual components of primary EP

N Engl J Med 2004;351:2049-57.

a heft study results
A-HeFT Study: Results
  • Study terminated early after mean duration of 10 months
  • Mortality was decreased by 43% with HYD/ISDN
  • Hospitalizations decreased by 33% (p=0.01)
  • QoL scores improved (p=0.01)

N Engl J Med 2004;351:2049-57.

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

nitrates and hydralazine80
Nitrates and Hydralazine
  • Class IIa: The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACEI and beta-blocker for symptomatic HF and who have persistent symptoms. (Level of Evidence: A)
  • Class IIa: The addition of isosorbide dinitrate and hydralazine to a standard medical regimen for HF, including ACEIs and beta-blockers, is reasonable and can be effective in blacks with NYHA functional class III or IV HF. Others may benefit similarly, but this has not yet been tested. (Level of Evidence: A)
antiplatelets anticoagulants
Antiplatelets & Anticoagulants
  • ASA reduces risk of CV events in patients without CHF but this has not been demonstrated in CHF patients
    • Concern that ASA may attenuate the hemodynamic and prognostic benefits of ACEIs
    • If ASA is needed (ischemic patient), the dose should be < 160 mg/day
  • Anticoagulants
    • Risk of TE is low (1-3%/year)
    • Reserved for patients with paroxysmal or chronic atrial fibrillation or a previous TE
medications to avoid
Medications to Avoid
  • Class III: All antiarrhythmics (except amiodarone and dofetilide) should be avoided because of increased mortality. (Level of Evidence: A)
  • Class III: Calcium channel blockers, only vasoselective (amlodipine) agents have not adversely effected survival. (Level of Evidence: A)
  • Class III: NSAIDs, promote sodium retention, inhibit renal blood flow. (Level of Evidence: A)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

step 3 recommend optimal pharmacotherapy83
Step 3: Recommend optimal pharmacotherapy
  • Review medication profile for contraindicated medications
    • CCBs, NSAIDs, 2-agonists, thiazolidinediones, metformin
  • Review OTC and herbal medications for contraindicated medications
    • NSAIDs, Sympathomimetics, Weight loss products, St. John’s Wort
device therapy
Device therapy
  • Implantable Cardioverter-defibrillator (ICD)
  • Cardiac resynchronization therapy (CRT)
implantable cardioverter defibrillator icd therapy secondary prevention
Implantable Cardioverter-defibrillator (ICD) therapy: secondary prevention
  • Class I: An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia.

(Level of Evidence: A)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

icd therapy primary prevention
ICD therapy: primary prevention
  • Class I: ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with ischemic heart disease who are > 40 days post-MI, have an LVEF < 30%, with NYHA FC II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: A)
  • Class I: ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with nonischemic cardiomyopathy who have an LVEF < 30%, with NYHA FC II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: B)

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

icd therapy primary prevention87
ICD therapy: primary prevention
  • Class IIa: Placement of an ICD is reasonable in patients with LVEF of 30 – 35% of any origin with NYHA FC II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year. (Level of Evidence: B)

“Now, this is critical: Here we see the patient’s wallet, and a closer look reveals an expired insurance card. This patient clearly does not qualify for an ICD.”

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

cardiac resynchronization therapy crt
Cardiac resynchronization therapy (CRT)

The COMPANION Study Secondary Endpoint: Total Mortality

  • Class I: Patients with LVEF < 35%, sinus rhythm, and NYHA FC III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 0.12 ms, should receive CRT unless contraindicated.

(Level of Evidence: A)

N Engl J Med 2004;350:2140-50.

Available at http://www.acc.org/clinical/guidelines/failure/index.pdf

summary of current treatment of chronic heart failure
Summary of Current Treatment of Chronic Heart Failure
  • ACE Inhibitors for all patients (NYHA-FC I-IV)
  • Beta-blockers for all patients
    • Use in NYHA I-III, carefully in IV
    • Use either metoprolol XL, bisoprolol, or carvedilol
  • ARBs for ACE intolerant patients
    • Use candesartan or valsartan
  • Nitrates & Hydralazine for patients intolerant to ACEIs and ARBs
summary of current treatment of chronic heart failure90
Summary of Current Treatment of Chronic Heart Failure
  • Spironolactone for NYHA III/IV on standard therapy
    • Provided they have adequate renal function and can be monitored closely (BUN/SCr and K+)
    • Eplerenone for post-MI patients with LV dysfunction or those with gynecomastia from spironolactone
  • Addition of ARB to ACE inhibitor & beta-blocker
    • Consider if patient with consistent symptoms
    • Do not use combine ACEI + Aldosterone antagonist + ARB. NO DATA!
heart failure drug therapy algorithm

Assess volume status

Signs & symptoms of fluid retention

No signs & symptoms of fluid overload

  • Diuretic
  • (titrate to euvolemia)
  • ACE inhibitor
  • Digoxin

Assess volume status

  • Beta-blocker

Assess volume status

  • Aldosterone Antagonists

Assess volume status

 ARBs

 ISDN/HYD

Heart Failure Drug Therapy Algorithm
chf precipitating factors
CHF: Precipitating Factors
  • Non-compliance is the leading cause of rehospitalization for patients with CHF.
step 4 follow up
Step 4: Follow-up
  • Monitor for compliance with therapy and lifestyle modifications
    • Adverse effects
    • $$$
  • Review weight diary
  • Assess current functional status
  • Given current functional status, assess if pharmacotherapy is optimal
step 4 follow up95
Step 4: Follow-up
  • Compliance enhancers
    • Pill Boxes
    • Personalized schedule
chf mortality room for improvement
CHF mortality: room for improvement?

CIBIS II MERIT-HF (1999)

SOLVD (1991)

% mortality at 1 year

28

24

15.6

12.4

11.9

7.8

Diuretic

Digoxin

Diuretic

Digoxin

ACE-I

Diuretic

Digoxin

ACE-I

Males*

(1990-1999)

Females*

(1990-1999)

Diuretic

Digoxin

ACE-I

Beta-Blocker

*Framingham Heart Study; NEJM 2002;347:1397-402.

adherence to guidelines
Adherence to Guidelines
  • Medicare patients discharged with diagnosis of CHF during 1997-1999
    • Median percentage of patients (from all 50 states) discharged with a prescription for an ACEI was 69%.
  • Patients on target dose of ACEI ranged from 12-48%
  • Beta-blocker utilization 40-50%

Jencks SF, et al. JAMA 2000;284:1670-6.

Sueta C et al. Am J Cardiol 1999;83:1303-7.

Circulation 1999; 100(suppl I):I-538.

J Am Coll Cardiol 2002; suppl.:166A.

adherence to guidelines99
Adherence to Guidelines
  • New Mexico Medicaid Retrospective DUR CHF intervention
    • 694 patients identified with diagnosis of CHF but without a prescription for either an ACEI or B (3/99-5/99)
    • An educational intervention packet discussing the use of B and ACEI therapy was mailed to prescribers (n=583), community pharmacists (n=196) and consultant pharmacists (n=26)
    • Short-term (3 month) and long-term (18 month) outcomes were evaluated

J Cardiac Failure 2001;7:80 [Abstract 320]

adherence to guidelines nm dur results
Adherence to Guidelines: NM DUR results
  • Response Rates
    • Prescribers 36%
    • Comm. RPh’s 35%
    • Conslt. RPh’s 46%
  • Responder’s indicating (+) change
    • Prescribers 11%
    • Comm. RPh’s 43%
    • Conslt RPh’s 46%

J Cardiac Failure 2001;7:80 [Abstract 320]

adherence to guidelines nm dur results101
Adherence to Guidelines: NM DUR results

J Cardiac Failure 2001;7:80 [Abstract 320]

adherence to guidelines nm dur results102
Adherence to Guidelines: NM DUR results
  • Responders indicating they would not consider changes
    • Prescribers 81%
    • Comm. Pharmacists 43%
    • Cnslt. Pharmacists 46%
  • Reasons
    • Top reason: Patient stable on current regimen
    • No longer a patient
    • C/I’s to ACEI (cough, RI) or B (COPD or asthma)

J Cardiac Failure 2001;7:80 [Abstract 320]

final step
Final step
  • Document your interventions!!!
    • It is vital for reimbursement for services
  • Write a SOAR note for your files and to send to patients PCP
    • Subjective
    • Objective
    • Assessment
    • Recommendation
slide104

Questions???

DiPiro

“Dr. Anderson, may I be excused? My brain is full.”