aeshah al-azmi (bnp and hf)

8/7/2019 Aeshah Al-Azmi (BNP and HF)..

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Aeshah Al-AzmiPharm.D candidate

Decmebr,14,2010


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objective

Patient casePatient case

IntroductionIntroduction

NatureticNaturetic peptidepeptide

BNP (pathophysiology and action)BNP (pathophysiology and action)

Role in HF (clinical trial)Role in HF (clinical trial)

ConclusionConclusion


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Patient casePatient case

HPI:71 years old man numerous hospitalized for management of heart failure (SOB,

orthopnea), renal failure. He has end stage ischemic cardiomyopathy. Left

ventricular systolic function was severely decreased with EF range (25%-30%).

Denies chest discomfort, palpitations, dizziness, or syncope

Medication:

Albuterol, allopurinol,amiodaron, aspirin, bumetanide, carvedilol,furosemide, glipizide, rosuvastatin, spironolactone

PMH:

HF

ARF (contrast, aggressive diuresis)

Hypothyroidism

DM

Peripheral vascular disuse


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Lab finding

12/07 12/08 12/09

Na 134 136 137

K 3.8 4 3.9

BUN 60 70 74

SCr 2 2.2 2.2

GFR 33 30 30

BNP 1060 1790 819

BP:121/70, RR: 16

Vital signs: neck vein distention notedHeart: sounds were heard with decreased intensity

Lungs: diffuse wheezing bilaterally

Abdomen: Obese, soft, non-tender

No significant ankle edema


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Heart failure (HF ) is the major cardiovascular disorder and a leading cause of death,

hospitalization, and re-hospitalization

The incidence and prevalence increases as the population ages

Management of HF includes use of therapies based on symptoms, signs

HF is difficult to diagnose in the ED as the symptoms may be nonspecific, and

physical findings are not sensitive enough to use as a basis for an accurate

diagnosis

Despite advances in medical treatment, deaths due to HF have increased 145% inthe last 20 years


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NYHA

Levels Description

ACC/AHA

Stages Description

I

Cardiac disease without resultinglimitations of physical activity.

A

Patients at high risk of developing HF because of the presence ofconditions that are strongly associated with the development of HF.Such patients have no identified structural or functional abnormalitiesof the pericardium, myocardium or cardiac valves and have never

shown signs or symptoms of HF

II

Slight limitation of physical activity -comfortable at rest, but ordinaryphysical activity results in fatigue,dyspnea, or anginal pain. B

Patients who have developed structural heart disease that is stronglyassociated with the development of HF but who have never shownsigns or symptoms of HF.

III

Marked limitation in physical activity -comfortable at rest, but less than

ordinary physical activity causesfatigue, dyspnea, or anginal pain.

C Patients who have current or prior symptoms of HF associated withunderlying structural heart disease

IV

Inability to carry on any physicalactivity without discomfort ofsymptoms at rest. D

Patients with advanced structural heart disease and markedsymptoms of HF at rest despite maximal medical therapy and whorequire specialized interventions.

HF classificationHF classification

ACC = American College ofCardiology

AHA = Americal Heart AssociationNYHA = New York Heart AssociationHF = Heart Failure


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Diagnostic studies:Diagnostic studies:

Echocardiography is considered the gold standard for the detection of LVD:

expensive

not always easily accessible

not always reflect an acute condition

LAB: BNP, C-reactive protein, HCT/Hgb (anemia), electrolytes, TSH, BUN/Creatinine,

LFTs (right-sided), Cardiac enzymes, HIV

CXR: pulmonary edema, pleural effusions, heart enlargement.

EKG: Non-specific changes, arrhythmias, ischemic changes

CT/MRI, and Cardiac catheterization

**BNP, has been investigated in numerous studies and found that it has potentially

important diagnostic, therapeutic, and prognostic implications.


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Natriuretic Peptides:

Neurohormones Internal compensatory mechanism forintravascular volume changes

Three types:

Atrial Natriuretic Peptide (ANP)

Brain-type Natriuretic Peptide (BNP)

C-type Natriuretic Peptide (CNP)


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Natriuretic PeptidesNatriuretic Peptides

Natriuretic

Peptide

Where

Manufactured

When Secreted Actions

ANPAtria Atrial Stretch Natriuresis,

Diuresis, qBP,

qRenin

BNP Ventricles Ventricular Stretch

Natriuresis,

Diuresis, qBP,

qRenin

CNP Endothelium Local Response Potent Venodilator


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BNP actions


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ANP BNP

Plasma half-life 3 Minute 21 Minute

Release stimulus Atrial transmural

tension

Ventricular wall tension

Synthesis site Cardiac atrium Cardiac ventricle

Physiological actions Natriuresisvasodepression

inhibition, RAA system

antimitogenesis

Natriuresisvasodepression

inhibition, aldosterone

? antimitogenesis

BNP Consensus Panel 2004

In case of fluid overload may cause rapid BNP production in both heart chambers,

and production in the atrium may exceed the amount of ANP.

the major source of plasma BNP is cardiac ventricles, suggesting that BNP may be amore sensitive and specific indicator of ventricular disorders than other natriureticpeptides


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BNP B-type natriuretic peptide (BNP) is a cardiac neurohormone that is produced and

synthesized from heart muscle cells, mainly in the left ventricular myocardium but

also in the atrial myocardium, as a pro-hormone and released into the cardiovascular

system in response to ventricular dilation and pressure overload

secreted amounts increased as we age

women secreting more than men.

Normal levels are less than 100 pg/m

Measured at admission, discharge, or any major change in treatment


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BNP role in HF

Diagnosis


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The Breathing Not Properly studyThe Breathing Not Properly studyStudy design and method:

large, multinational, prospective study using BNP to evaluate dyspnea in

1586 ED patients. BNP levels were measured on arrival, BNP cut point is

100 pg/mL and physicians assessed the probability of the patient having

HF. Two cardiologists, blinded to the BNP level, reviewed all data after

hospitalization to produce a "gold standard" clinical diagnosis

Maisel A, Krishnaswamy P, Nowak RM, et al. Rapid measurement ofB-type natriuretic peptide in the emergency diagnosis of heartfailure. N Engl J Med. 2002;347(3):161167


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Result:

BNP levels alone more accurately predicted the presence or absence of HF than

any other finding. The 100 pg/mL cutpoint had a 90% sensitivity and 76%

specificity for a HF diagnosis

Conclusion:

BNP levels contributed to the diagnosis, even after considering features of the

history and physical examination

Maisel A, Krishnaswamy P, Nowak RM, et al. Rapid measurement ofB-type natriuretic peptide in the emergency diagnosis of heartfailure. N Engl J Med. 2002;347(3):161167


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BHP Consensus Panel. CHF. 2004; 10[5 suppl 3]:130)2004


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BNP role in HF

Diagnosis

Prognosis


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Objective

To assess how well B-type natriuretic peptide (BNP) predicts

prognosis in patients with heart failure.

Design :

Systematic review of 19 studies used BNP to estimate the relative

risk of death or cardiovascular events in heart failure patients and

five studies in asymptomatic patients.

How well does B-type natriuretic peptide predict death and

cardiac events in patients with heart failure: systemic

review


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Results:

In heart failure patients, each 100 pg/ml BNP increase was

associated with a 35% increase in the relative risk of death.

Conclusion:

results of the studies in this review show that BNP is a strong

prognostic indicator for both asymptomatic patients and for

patients with heart failure at all stages of disease.


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BNP role in HF

Diagnosis

Prognosis

Guide HF therapy


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STARS-BNP trial

Aim:to demonstrate improved outcomes using a natriuretic peptide guided approach in

patients with HF, goal of decreasing BNP plasma levels


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Jourdain P, JondeauG, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, AumontMC, Galinier M, Eicher JC, Cohen-Solal A, Juillire Y. Plasma brain natriuretic peptide-guided therapy to improve outcome in

heart failure: the STARS-BNP Multicenter Study.. J Am Coll Cardiol 2007;49:1733-9

Clinical outcomes after at least six months of therapyClinical outcomes after at least six months of therapy

(median, 15 months)(median, 15 months)


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Treatment modifications in the STARS-BNP trial


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Changes in per-patient use of evidence-based medical therapy

during first three months (mean % of recommended dosage

received)

Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A , Donal E, Au petit JF, Aumont MC, Galinier M, Eicher JC, Cohen-Solal A, Juillire Y. Plasma brain natriuretic peptide-guided therapy to improve outcome in



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Comment:

BNP-guided management showed a significant

decrease in the primary end point of death or

unplanned hospitalization due to heart failure,fewer HF-related hospitalizations, and better

event-free survival

Jourdain P, JondeauG, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, AumontMC, Galinier M, Eicher JC, Cohen-Solal A, Juillire Y. Plasma brain natriuretic peptide-guided therapy to improve outcome in



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Identification and guided treatment of ventricular dysfunction in

general practice using blood B-type natriuretic peptide

Aim:

To assess the practical implications and potential clinical benefit of measuring

BNP to identify and guide the treatment of undiagnosed or under treated

ventricular dysfunction in at-risk patients

Br J Gen Pract. 2008 June 1; 58(551): 393399.


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Study design and

method



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Medication prescribed at the beginning and end ofBNP-guided

treatment titration (n = 76)

Angiotensin inhibitor

without beta-blocker

Beta-blocker

without

angiotensin

inhibitor

Both beta-

blocker and

angiotensin

inhibitor

Neither beta-

blocker nor

angiotensin

inhibitor

Spironolactone Furosemide

Entry 12 (15.8) 24 (31.6) 30 (39.5) 10 (13.2) 3 (3.9) 17 (22.4)

Exit 11 (14.5) 5 (6.6) 56 (73.7) 4 (5.3) 9 (11.8) 19 (25.0)

n %n %

aAngiotensin inhibitors on entry were ramipril (n = 11), lisinopril (n = 11), enalapril (n = 4), other ACE inhibitors (n = 5), angiotensin II receptorblockers (n = 11); beta-blockers on entry were atenolol (n = 32), bisoprolol (n = 10), metoprolol (n = 5), sotalol (n = 5), carvedilol (n = 1),nebivolol (n = 1).



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About 10% (76) of patients with diabetes or cardiovascular disease registers

have a persistently raised plasma BNP concentration. Simple adjustment of their drug

treatment has the potential to reduce theirBNP concentration and associated mortality

risk significantly

Br J Gen Pract. 2008 June 1; 58(551): 393399


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B-Type Natriuretic PeptideGuided Heart Failure Therapy

Aim:Examine the overall effect ofBNP-guided drug therapy on cardiovascular

outcomes in patients with chronic HF

Methods:Meta-analysis of prospective randomized controlled trials.

Eight studies involving 1,726 patients, published internationally from 2005-2009

comparing ofBNP-guided drug therapy vs usual clinical care of the patient with

chronicHF in an outpatient setting

Study sizes ranged from 41 to 499 patients, (3-24 month) follow-upPatients had NYHA class II or greater heart failure, with ejection fractions


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Results

All-cause mortality was significantly lower in BNP-guided therapy compared

with clinical-guided therapy (RR=0.76; 95% CI, 0.63-0.91; P=0.003),

specifically in patients younger than 75 years old (RR=0.52; 95% CI, 0.33-0.82;

P=0.005).

there was no reduction in mortality with BNP-guided therapy in patients 75

years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70)

Arch Intern Med. 2010;170(6):507-514


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Trial name andreference

N Study populationNatriuretic peptide

targetControl group(s) Follow-up Primary endpoint(s)

The ChristchurchNew Zealand pilot

trial[41]69

Enrolled at hospital dischargeLVEF


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PROTECT trial

study design:

small, single-center, randomized trial supports the

strategy of heart-failure medication adjustment guided by

assessments of natriuretic-peptide levels

151 patients enrolled all received standard therapy (75

adjusted medication guided by BNP)

P = .03 for SOC followP = .03 for SOC follow--up versus NTup versus NT--proBNPproBNP followfollow--up 44.3% ofNTup 44.3% ofNT--proBNPproBNP subjectssubjectsee10001000 pgpg/mL/mL


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methodsmethods

Inclusion Criteria

Age > 21 years ofage

Left ventricularejection fraction 40%

New York Heart Association class II-IV symptoms

Hospitalization, ED visit, oroutpatient therapy forADHF within6 months

Exclusioncriteria

Serum creatinine > 2.5 mg/dl

Inoperable aorticvalve disease

Life expectancy


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Baseline characteristic

Characteristic NT-proBNP (N=75) SOC (N=76) P

Age, years 63.0 14.5 63.5 13.5 .41

LV ejection fraction (%) 28.0 8.7 25.9 8.3 .52

NYHA Class II orIII (%) 65 (85.5) 64 (84.2) .46

Male gender (%) 67 (88.2) 61 (81.3) .24

Caucasian (%) 65 (85.5) 66 (88.0) .65

Cause of heart failure

Ischemic (%)Non-ischemic (%)Other (%)

40 (53.3)25 (33.3)10 (13.3)

45 (60.0)18 (24.0)12 (16.0)

.17

Past medical historyHypertension (%)Coronary artery disease (%)Myocardial infarction (%)Atrial fibrillation (%)Ventricular tachycardia (%)Obstructive airways disease (%)Diabetes mellitus (%)

40 (52.6)42 (55.3)28 (36.8)31 (40.8)23 (30.3)15 (19.7)30 (39.5)

39 (52.0)50 (66.7)30 (40.0)30 (40.0)21 (28.0)16 (21.3)32 (42.7)

.94

.09

.69

.92

.76

.81

.19

Implanted devicesCardioverter-defibrillator (%)Biventricular pacemaker (%)

52 (69.3%)30 (40.0%)

50 (65.8%)30 (39.4%)

.70

.68

P = .03 for SOC followP = .03 for SOC follow--up versus NTup versus NT--proBNPproBNP followfollow--up 44.3% ofNTup 44.3% ofNT--proBNPproBNP subjectssubjectsee10001000pgpg/mL/mL


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HF baseline therapy

MedicationBaseline

NT-proBNP (N=75) SOC (N=76) P

ACE Inhibitors (%) 53 (70.7) 47 (61.8) .21

Angiotensin receptor blocker (%) 8 (10.7) 15 (19.7) .11

blocker (%) 74 (98.7) 71 (93.4) .19

Aldosterone antagonist (%) 37 (49.3) 26 (34.2) .10

Loop Diuretics (%) 67 (89.3) 71 (93.4) .27

Thiazide Diuretic (%) 5 (6.7) 3 (4.0) .48

Digoxin (%) 22 (29.3) 25 (32.9) .89

Hydralazine (%) 4 (5.3) 4 (5.3) .89

Nitrates (%) 8 (10.7) 16 (21.1) .07

P = .03 for SOC followP = .03 for SOC follow--up versus NTup versus NT--proBNPproBNP followfollow--up 44.3% ofNTup 44.3% ofNT--proBNPproBNP subjectssubjectsee10001000 pgpg/mL/mL


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HF titrationoftherapy

Medication Titration

NT-proBNP (N=75) SOC (N=76) P

ACE Inhibitors (%) +25.4% +18.1% .15

Angiotensin receptor blocker (%) +5.8% +22.3% .01

blocker (%) +46.0% +34.5% .05Aldosterone antagonist (%) +22.7% +5.8%


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Care of patients with HF requires both inpatient acute care and outpatient

chronic care. Pharmacists can play an important role in appropriate therapy

selection, monitoring, and education in both settings. It is important forpharmacists caring for patients both in the acute setting and in the chronic

setting to be updated and knowledgeable on the recommendation changes in

HF care.

Pharmacist role


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Conclusion

BNP is secreted by the heart in response to increased

volume, useful in the diagnosis heart failure

BNP plasma levels strongly associated with the presence

and severity of H

levels be decreased by treatment with proven heart failure

medications and associate with favorable outcome

BNP can be used as guided HF therapy


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Aeshah Al-AzmiPharm.D candidate

Decmebr,14,2010

aeshah al-azmi (bnp and hf)

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