decompensated heart failure - cecity · comorbidities: diabetes 20-25% renal insufficiency:...
TRANSCRIPT
Decompensated Heart Failure:
Focusing on Early and Aggressive Treatment to
Improve Patient and Economic Outcomes
Clyde W. Yancy, M.D.University of Texas Southwestern Medical Center
Dallas
Adapted from HFSA. Pharmacotherapy. 2000;20:495.
Evolution to Cardiovascular Events; What causes heart failure?
SNS-RAS SNS-RAS
MetabolicSyndrome
(Insulin resistance, diabetes)
HTN
MI Cardio-myopathy
HF
Heart FailureHeart Failure--How does it How does it happen?happen?
Myocardial injuryMyocardial injury Fall in LV performanceFall in LV performance
Activation of RAAS, SNS, ET,Activation of RAAS, SNS, ET,and othersand others
Myocardial toxicityMyocardial toxicity Peripheral vasoconstrictionPeripheral vasoconstrictionHemodynamicHemodynamic alterationsalterations
Remodeling andRemodeling andprogressiveprogressiveworsening ofworsening ofLV functionLV function Heart failure symptomsHeart failure symptomsMorbidity and mortalityMorbidity and mortality
ANPANPBNPBNP
-
-
Acute MI(hours)
Infarct expansion(hours to days)
Global remodeling(days to months)
Example of Post-MI Remodeling
• Apical infarction from total occlusion LAD,remainder of coronaries without obstruction
Reversal of Remodeling With Pharmacologic Treatment
Cardiac adrenergic,RAS signaling
Myocytedysfunction
Improved myocyte function
Antiadrenergictherapy
Remodeledventricle
Relatively normal chamber size &
geometry
Survival Benefit: ACEIs and ß-Blockers-is mortality still an issue?
15.6
11.9
7.8
12.4
0
2
4
6
8
10
12
14
16
Placebo Active treatment
% SOLVD-TMERIT-HF +CIBIS II
Death at 1 Year
Adapted from McMurray JJV. Heart. 1999;82(suppl IV):IV14–IV22.
? Additional benefit Of aldosterone antagonism
*annual mortalityRate in Val-HeFT:6%*
Congestive Heart Failure:A New Problem Emerges
• Nearly 900,000 annual hospital admissions(increased 90% in past 10 years)1
• Most common discharge diagnosis for patients older than 65 years2
• 6.5 million hospital days per year1
• Single largest expense for Medicare1
• 0.9% of members with HF incur 4% of health plan costs with mean annual charges of $6,0263
1. Hunt SA et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult.2001.
2. Graves EJ, Gillum BS. 1994 Summary: National Hospital Discharge Survey. National Center for Health Statistics; 1996.
3. DeLissovoy G et al. Treatment Charges & Resource Use Among Patients with HF Enrolled in an MCO.Managed Care Interface, May, 2002.
Heart Failure HospitalizationsThe Number of Heart Failure Hospitalizations Is Increasing
in Both Men and Women
CDC/NCHS: hospital discharges include patients both living and dead.
Ann
ual D
isch
arge
s
0
100,000
200,000
300,000
400,000
500,000
600,000
'79 '81 '83 '85 '87 '89 '91 '93 '95 '97
WomenMen
Year'99
American Heart Association. 2002 Heart and Stroke Statistical Update. 2001.
Rates of Hospital Re-admission
0
10
20
30
40
50
60
Within 2Days
Within 1Month
Within 6Months
Patie
nts
Rea
dmitt
ed (%
)
2%
20%
50%
Aghababian RV. Rev Cardiovasc Med. 2002;3(suppl 4):S3–S9.
Outcomes of Heart Failure Hospitalizations
• Median length of hospital stay: 6 days1
• Hospital readmissions– 20% at 30 days1
– 50% at 6 months1
• Mortality– 11.6% at 30 days2
– 33.1% at 12 months2
– 50% at 5 years1
1. Aghababian RV. Rev Cardiovasc Med. 2002;3(suppl 4):S3–S9.2. Jong P et al. Arch Intern Med. 2002;162:1689–1694.
ADHERE-An Acute Decompensated Heart Failure Registry
Gaps in Knowledge Before ADHEREGaps in Knowledge Before ADHEREClinical Trials:
Age: 50-60’s years old
Sex: 70-80% Men
Comorbidities: Diabetes 20-25%Renal Insufficiency: infrequent (mean Cr 1.1-1.3)
Ventricular Function: 75-80% Systolic Dysfunction (LVEF < 0.40)
PAC use: 30-40%
In-hospital Mortality: 1.5-2.5%
Goals of the ADHERE RegistryGoals of the ADHERE Registry
• Describe demographics and clinical characteristics of patients hospitalized with acutely decompensatedheart failure (AHF)
• Characterize current management of hospitalized patients with AHF
• Define treatment strategies associated with best clinical outcomes and most efficient use of resources
• Assist in evaluating and improving the quality of care
Cumulative Patient Enrollment
38,31044,240
51,06956,805
63,321
70,55976,491
31,00036,00041,00046,00051,00056,00061,00066,00071,00076,00081,00086,000
12/30/02 2/28/03 4/29/03 6/28/03
Cumulative Patient Enrollment
As of 10/03, >100,000 entries are in the ADHERE Database
Executive SummaryAll Enrolled Discharges in the Last 12 Months (07.01.2002-06.30.2003)
The Nationn=58919Demographics/Patient Characteristics
557 (n=33572)
46
Chronic Renal Dialysis (%)LVEF Measured In-hospital (%)
LVEF <40% or Mod/Sev Impairment (%)
4852
GenderMale (%)Female (%)
75.348
Median Age (yrs)Patients >75 Years (%)
Indented percentages are calculated based on the number of patients presented in the preceding row, rather than the number of patients for the column.
Utilization of Evidence-based Therapies in Heart Failure
2300/7883 Patients hospitalized with HF; prior known dx of systolic dysfunction HF; outpatient medical regimen.ADHERE Registry Report Q1 2002 (4/01-3/02) of 180 US HospitalsPresented at the Heart Failure Society of America Satellite Symposium, September 23, 2002.
50.8
12.8
57.4
80.8
41
0102030405060708090
100
Outpatient HF Medication
Patie
nts
Trea
ted
(%)
History of HF and LVEF Documented and ≤ 0.40*
*Excludes patients with documented contraindications.
ACE Inhibitor ARB β -Blocker Diuretic Digoxin
Most Common IV Medications
0102030405060708090
100
% o
f Pat
ient
s
IV Diuretic Dobutamine Dopamine Milrinone Nesiritide Nitroglycerin Nitroprusside
IV Vasoactive Meds
88%
6% 6% 10%3%
All Enrolled Discharges (n=105388) from October 2001 to January 2004
1%10%
4.04.75.41.4
In-hospital Mortality (%)Mechanical Vent (%)Renal Dialysis (%)Defibrillation or CPR (%)
Adverse Outcomes
4.35.0 (n=46835)
4.1 (n=58919)
2.5 (n=11074)
Median Total Hospital LOS (days)Median ED and/or Obs LOS (hrs)Median Inpatient Hospital LOS (days)
Median ICU LOS (days)
The Nation n=58919
LOS
All Enrolled Discharges in the Last 12 Months (07.01.2002-06.30.2003) Executive Summary (Continued)
Indented percentages are calculated based on the number of patients presented in the preceding row, rather than the number of patients for the column.
INTRODUCING A NEW PARADIGM IN
CARDIOVASCULAR DISEASE:
Heart Failure and Mortality in the
ADHERE Database:What Have We
Learned?
Mortality Data Mining ProcessMortality Data Mining ProcessMortality Data Mining ProcessStep 1Step 1
Defining Covariate Adjusted Odds Ratios of Death
Defining Covariate Adjusted Defining Covariate Adjusted Odds Ratios ofOdds Ratios of DeathDeath
All Covariates
Risk Stratification Modeling
Predictors of Death (i.e.)• BUN• CREATININE• SPBP• SODIUM• AGE• SEX
All Covariates
Propensity Modeling Software
Predictors of Treatment (i.e.)• BUN• CREATININE• SPBP• SODIUM• AGE• SEX
Step 2Step 2Defining Covariate Adjusted
Probability of Treatment“propensity score”
Defining Covariate Adjusted Defining Covariate Adjusted Probability ofProbability of TreatmentTreatment
“propensity score”“propensity score”
Risk and Propensity
Adjusted OR of Death
CART CART
AgeAge Qualitative LVEF / PreQualitative LVEF / Pre--hosp/init hosp/init evalevalLength of stayLength of stay--inpatientinpatient GenderGenderTime in careTime in care Race / ethnicityRace / ethnicity DyspneaDyspnea categorycategoryHF: preHF: pre--hospitalhospital Primary InsurancePrimary Insurance FatigueFatigueFirst weightFirst weight Ischemic EtiologyIschemic Etiology RalesRalesFirst heightFirst height HF: Baseline NYHA classHF: Baseline NYHA class Peripheral EdemaPeripheral EdemaFirst systolic BPFirst systolic BP CADCAD NYHA Class IV / PresNYHA Class IV / PresFirst diastolic BPFirst diastolic BP CAD: Prior MICAD: Prior MI Congestion / 1Congestion / 1stst xx--rayrayheart rateheart rate CAD: Prior revascularizationCAD: Prior revascularization QRS duration >120 msQRS duration >120 msSodiumSodium AtrialAtrial fibrillationfibrillation Cardiac enzymesCardiac enzymesCreatinineCreatinine DiabetesDiabetes HBG < 12HBG < 12BUNBUN HypertensionHypertension Duration of symptomsDuration of symptomsBUN / BUN / CreatinineCreatinine ratioratio HyperlipidemiaHyperlipidemia Tachycardia >100Tachycardia >100HemoglobinHemoglobin Stroke / TIAStroke / TIA HypertensiveHypertensive--SBP >140SBP >140BNPBNP Ever smokedEver smokedKirk Adams HF scoreKirk Adams HF score DyspneaDyspnea typetype
ADHERE: Potential Predictors of ADHERE: Potential Predictors of InIn--Hospital MortalityHospital Mortality
AgeAge Qualitative LVEF / PreQualitative LVEF / Pre--hosp/init hosp/init evalevalLength of stayLength of stay--inpatientinpatient GenderGenderTime in careTime in care Race / ethnicityRace / ethnicity DyspneaDyspnea categorycategoryHF: preHF: pre--hospitalhospital Primary InsurancePrimary Insurance FatigueFatigueFirst weightFirst weight Ischemic EtiologyIschemic Etiology RalesRalesFirst heightFirst height HF: Baseline NYHA classHF: Baseline NYHA class Peripheral EdemaPeripheral EdemaFirst systolic BPFirst systolic BP CADCAD NYHA Class IV / PresNYHA Class IV / PresFirst diastolic BPFirst diastolic BP CAD: Prior MICAD: Prior MI Congestion / 1Congestion / 1stst xx--rayrayheart rateheart rate CAD: Prior revascularizationCAD: Prior revascularization QRS duration >120 msQRS duration >120 msSodiumSodium AtrialAtrial fibrillationfibrillation Cardiac enzymesCardiac enzymesCreatinineCreatinine DiabetesDiabetes HBG < 12HBG < 12BUNBUN HypertensionHypertension Duration of symptomsDuration of symptomsBUN / BUN / CreatinineCreatinine ratioratio HyperlipidemiaHyperlipidemia Tachycardia >100Tachycardia >100HemoglobinHemoglobin Stroke / TIAStroke / TIA HypertensiveHypertensive--SBP >140SBP >140BNPBNP Ever smokedEver smokedKirk Adams HF scoreKirk Adams HF score DyspneaDyspnea typetype
3 Greatest Predictors of IHM3 Greatest Predictors of IHMVariable Predictors of IHMVariable Predictors of IHMNonNon--Predictors of IHMPredictors of IHM
ADHERE: Potential Predictors of ADHERE: Potential Predictors of InIn--Hospital MortalityHospital Mortality
ADHERE CART Analysis• Best single predictor for in-hospital mortality was high
admission BUN (>43 mg/dL)
• Next most useful predictor was low admission SBP (<115 mmHg)
• Third best predictor was a high admission creatinine (>2.75 mg/dL)
• These branch points allowed identification of patients with mortality rates as low as 2.14% and as high as 21.94%, odds ratio 12.9 (95% CI 10.4-15.9)
ADHERE CART Analysis
SYS BP 115n=24,933
SYS BP 115n=7,147
6.41%n=5,102
15.28%n=2,048
21.94%n=620
12.42%n=1,425
5.49%n=4,099
2.14%n=20,834
BUN 43N=32,324
GreaterGreaterthanthan
LessLessthanthan
2.68%n=25,122
8.98%n=7,202
Cr 2.75n=2,045
Fonarow et al., Accepted HFSA 2003Fonarow et al., Accepted HFSA 2003
%’s = mortality rates%’s = mortality rates
ADHERE Mortality AnalysisPatients Receiving IV Vasoactive Medications
• In ADHERE, therapies rendered were determined based on clinician judgment and not by a study protocol
• Imbalances between groups in baseline characteristics that both predicted mortality as well as the likelihood of receiving a given therapy were adjusted using multivariable regression and propensity analysis
Effects of IV Vasoactive Medications on Mortality in ADHERE
Abraham et al., Accepted HFSA 2003
0.41*0.57*0.83†Adjusted for covariates and propensity score
0.51*0.58*0.85§Adjusted for covariates
sex, age, BUN, SBP, DBP, CR
0.36*0.53*1.62*Unadjusted
Nesiritidevs.
dobutamine
Nesiritide vs.
milrinone
Nesiritide vs. NTG
Analysis
** pp<<0.0002, 0.0002, §§ p=0.24, p=0.24, ††p=0.19 p=0.19 Nesiritide n=2,128; NTG n=3,457; milrinone n=1,205; Nesiritide n=2,128; NTG n=3,457; milrinone n=1,205; dobutaminedobutamine n=2,211n=2,211
ADHERE Mortality Analysis
Nesiritide N = 2,128
Favors NesiritideFavors Nesiritide
NitroglycerinNitroglycerinN = 3,457N = 3,457
MilrinoneMilrinoneN = 1,205N = 1,205
DobutamineDobutamineN = 2,212N = 2,212
Favors Other AgentFavors Other Agent
0 1 2Hazard Ratio
P P = 0.186= 0.186
P P < 0.0002< 0.0002
P P < 0.0002< 0.0002
Utilization of inotropic agents versus nesiritide
Based on cumulative national benchmark report data
* Inotropes: Dobutamine, Dopamine, and milrinone
ADHERE National Benchmark Data
17%16%
15% 15%
7%
9%10%
12%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
Q4 2002 Q1 2003 Q2 2003 Q3 2003
Inotrope Use*Nesiritide Use
ADHERE CM- LESSONS LEARNED: RENAL
DYSFUNCTION
Prevalence of Renal Insufficiency in Hospitalized Heart Failure
5.0%
14.0%
20.0%
0.0%
5.0%
10.0%
15.0%
20.0%
Source: Scios ADHERE Registry April 2003. Note: P- values for categorical variables from Mantel-Haenszel Chi-square statistic.
SCr < 2.0mg/dL
N = 52,047
SCr 1.5- 2.0mg/dLChronic Dialysis
5.7%
3.5%
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%P-value = < 0.0001
Outcomes - Mortality
Summary of Patient Characteristics Renal Insufficiency vs. Without Renal Insufficiency
Renal Insufficiencyn = 765
Without Renal Insufficiencyn = 1,151
Source: Scios ADHERE Registry April 2003. Note: P- values for categorical variables from Mantel-Haenszel Chi-square statistic.
6.6
5.6
5.05.25.45.65.86.06.26.46.6
P-value = < 0.0001
Outcomes - Total Hospital LOS (days) Mean
Renal Insufficiencyn = 13,466
Without Renal Insufficiencyn = 33,125
Summary of Patient Characteristics Renal Insufficiency vs. Without Renal Insufficiency
Source: Scios ADHERE Registry April 2003. Note: P- values for categorical variables from Mantel-Haenszel Chi-square statistic.
Risk of Mortality in Relation toDecreasing LVEF and GFRc
HillegeHillege HL et al. Circulation 2000; 102: 203HL et al. Circulation 2000; 102: 203--1010
Baughman, et al. N Engl J Med 2002;347:158–159
Natriuretic peptides: ‘the opposition’
Pharmacologic Actions of Human BNP
RenaldiuresisnatriuresisGFR
Neurohormoralaldosterone, renin, AIIendothelinnorepinephrine
Hemodynamic(balanced vasodilation)• preload (veins)• afterload (arteries)• coronary arteries
DR IMKRG
S SSSGLGF
C CS SG
SGQVMK V L RR
H
KPS
Cardiac lusitropic anti-fibroticanti-remodeling
RAP = right arterial pressure.
Hemodynamic Effects ofNesiritide in CHF Patients
*P < 0.01 vs. baseline†P < 0.05 vs. placebo ‡P < 0.05 vs. baseline
–60
–40
–20
0
20
40
60
HR RAP PCWP SVR CI SVI
Placebo (n = 4)Nesiritide (n = 10)
Cha
nge
From
Bas
elin
e (%
)
* ‡
‡
* †
A Randomized, Double-Blind, Placebo-Controlled Trial
Abraham WT et al. J Cardiac Fail. 1998;4:37–44.
Plasma Aldosterone Plasma Norepinephrine
Nesirit
ide
0.015
µg/kg
/min
Nesirit
ide
0.030
µg/kg
/min
Placeb
o
- 2.5 ng/dL - 1.6 ng/dL 0.6 ng/dL
Nesirit
ide
0.015
µg/kg
/min
Nesirit
ide
0.030
µg/kg
/min
Placeb
o
- 75 pg/ml 8 pg/ml 36 pg/ml
Figure adapted from data published in Colucci WS et al. N Engl J Med 2000:343:246-53
Effects on Neurohormones at 6 Hours
P = 0.03P = ns
Effects of nesiritide vs. dobutamine on heart rate, premature ventricular beats (PVB),
and repetitive beats
Burger AJ, et al. Am Heart J 2002;144:1102–1108
PRECEDENTPRECEDENT
-20
0
20
40
60
80
Mean change from baseline in events/hour or average HR
(bpm)
P<0.001
P=0.001
P<0.001
Heart rate PVB Repetitive beats
Dobutamine (n=83)
Nesiritide 0.015 µg/kg/min (n=84)
Nesiritide 0.030 µg/kg/min (n=79)
Treatment Duration (h)0
Months6
Eligible Patients(N = 489)
Catheterized(n = 246)
Noncatheterized(n = 243)
Stratified Randomized
Nitroglycerin (n = 60)
Placebo (n = 62)
NES fixed dose (n = 62)
NES adjustable dose (n = 62)
Nitroglycerin (n = 92)
NES fixed dose (n = 92)
NES adjustable dose (n = 62)
3-Hour Placebo-Controlled Period
Active-Controlled Period
1 2 3
Nitroglycerin (n = 124)
Placebo (n = 80)
NES fixed dose (n = 119)
Nitroglycerin (n = 83)
NES fixed dose (n = 80)
End of Study Drug
Added to standard therapy
VMAC: Study Design
Scios Inc. NDA 20-920 Cardiovascular and Renal Drugs Advisory Committee Briefing Document: Natrecor (nesiritide) for Injection. Sunnyvale, CA: Scios Inc; May 25, 2001.
Nesiritide Hemodynamic Effects vs. IV NTGC
hang
e fr
om B
asel
ine
in P
CW
P (m
mH
g)
End of Placebo-Controlled Period
Time on Study Drug (Hours)
During 3-hour Placebo Period:Placebo, n = 62 IV NTG, n = 60Nesiritide, n = 124
After 3-hour PeriodIV NTG, n = 92Nesiritide, n = 154
† P ≤ 0.05 vs. IV NTG* P ≤ 0.05 vs. Placebo
†*
Publication Committee for the VMAC Investigators. JAMA 2002: 287(12); 1531-1540
0 0.25 0.5 1 2 3 6 9 12 24 36 48
-9
-8
-7
-6
-5
-4
-3
-2
-1
0PCWP - Placebo
PCWP - IV NTG
PCWP - Nesiritide
†*
†* †
** †
* †
†††
*
Pharmacoeconomics of Heart Failure Treatment
Loma Linda Experience
• Review of 130 consecutive patients discharged from the CCU
• Data on patient demographics, medication usage and outcomes
• Patients divided into two groups, 58 nesiritide and 72 controls
Effect of Nesiritide on Length of Hospital Stay in Decompensated Heart Failure. Chang R et al. ACC Poster Presentation April 2003.
Loma Linda Experience: Baseline Characteristics
Age 58±22 66 ±22 .07EF 18±11 24 ±16 .023SBP 115 ±21 126 ±25 .011SCr 1.97±1.14 1.57 ±.85 .023BUN 50±39 40 ±27 .067
Nesiritide No Nes P-value
Loma Linda Experience: Results
2.81
1.971.86
3.88
1.57 1.56
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Nesiritide No Nes
LOS (p<0.001)Admit SCrDischarge SCr
Days or mg/dl
ADHERE: Loma Linda Experience
LomaLinda
Like Hospital
HospIn
Region
AllHospitals
Inpatient LOS
U of Kentucky (UK) Experience
• Retrospective study of 55 ADHF patients admitted to University of Kentucky HF service (29 nesiritide, 26 milrinone)– Primary outcomes
• Length of Stay (Overall, ICU, Floor)• Hospital readmission at 30 days
– Secondary outcomes• Length of medication infusion• Change in hemodynamics• Overall cost of therapy• Overall diuresis
Effect of Nesiritide vs. Milrinone on Patient Outcomes in the Treatment of Acute Decompensated Heart Failure. Lewis DA et al. To be presented at ACCP Spring Forum April 2003
Univ of KY Experience:Baseline Characteristics
0.71753 +/- 3.7055 +/- 3.59PAS
0.08322 +/- 1.5026 +/- 1.72PCWP
0.5641271 +/- 1061357 +/- 101SVR
0.65214 +/- 1.5215 +/- 1.69RAP
0.5232.2 +/- 0.162.4 +/- 0.22CI
0.40759 +/- 2.7462 +/- 2.37DBP
0.097114 +/- 3.77124 +/- 4.33SBP
0.001116.6 +/- 10.950.1 +/- 5.3Duration (hrs)
0.0481.42 +/- 0.171.87 +/- 0.14SCr (mg/dl)
0.30189 +/- 4.6296 +/- 4.96Weight (kg)
0.09357 +/- 2.9663 +/- 2.36Age
P-valueMilrinone (n=26)Nesiritide (n=29)
Effect of Nesiritide vs. Milrinone on Patient Effect of Nesiritide vs. Milrinone on Patient Outcomes in the Treatment of acute HFOutcomes in the Treatment of acute HF
Parameters Nes (N=29) Milrinone (N=25) P-v aluesBaseline SrCr 1.87 1.42 0.048Duration of Tx (hr) 50.1 116.6 0.001LOS (days) 7 8.2 0.328 ICU LOS 3.9 5.9 0.007 Floor LOS 3.1 2.3 0.46330-day readmit 16% 28% 0.306Dec PCWP/ 48 hrs 10.5 mmHg 4 mmHg 0.026
Lewis DA, PharmD et al. ACCP Spring Forum April ,2003
Univ of KY Experience: Secondary Outcomes
2985 ml2205 ml48 hours0.101823ml1067 ml24 hours
P-valueNesiritideMilrinoneDiuresis
$4,155$746$3,409Nesiritide$4,553$280$4,273Milrinone
Overall CostDrug CostHospital Cost(LOS)
Costs
Cleveland Clinic Experience
Hospital Floor• 159 admissions
• 22 Natrecor
– LOS 3.7 days
• 137 other therapy
– LOS 5.5 days
Observation Unit• 48 admissions
• 18 Natrecor
– 16 (89%) DC Home
• 30 other therapy
– 14 (47%) DC Home
Peacock WF. Rev Cardiovasc Med 2002;3(suppl 4):S41-S48.
LOS = length of stay; SC = standard care; ED/OU = emergency department/observation unit; APC = ambulatory payment classification; DRG = diagnosis-related group.Data on file. Scios Inc. August 2002.
Eligible CHF Patients(n = 250)
Nesiritide + SC(n = 120)
Standard Care (SC)(n = 117)
Outpatient Care(APC Code)
Inpatient Care(DRG Allowed)
53 Remain Stable After Discharge
64 Patients Admitted
49 Remain Stable After Discharge
51% Discharged (n = 61)
45% Discharged(n = 53)
59 Patients Admitted 6 Rehosp w/in 30 Days
4.6-Day LOS (index + readmit)
15 Patients Rehosp w/in 30 Days
8.3-Day LOS (index + readmit)
Readmission w/in 30 Days(No DRG Allowed)
ED/OU
≥12 hours
PROACTION: Emergency Medicine Pilot Trial
PROACTION: Outcomes
Index Admissions:
• 11% ↓ in all cause index admissions– 55% standard therapy, 49% nesiritide
• 21% ↓ in CHF index admissions– 38% standard therapy, 30% nesiritide
• 29% ↓ in Class III/IV index admissons– 42% standard therapy, 30% nesiritide
PROACTION: Outcomes
Re-admissions After Index:
• 57% ↓ in all cause readmissions– 23% standard therapy, 10% nesiritide
• 45% ↓ in total LOS (index + readmit)– 8.3 days standard therapy, 4.6 days nesiritide
Cost Analysis:• Improved outcomes neutralize cost
Hospital Length of Stay
ADHERE Registry: 14.7% of patients started IV therapy in the ED compared with 25.5% who started on admission; EmermanCL et al. Ann Emerg Med. 2002;40(4 pt 2):162.
ED vs. Inpatient Initiation of IV Vasoactive Therapy
0
3
6
9
12
15
Leng
th o
f Sta
y (d
)
ED Initiation Inpatient Initiation
IV Vasoactive Therapy
6.3
9.4p = 0.04
Conclusions• Several pharmacoeconomic analyses have shown
nesiritide use in ADHF patients to be cost-effective by:
– Reducing index admissions, or LOS (ICU and overall) for those requiring hospitalization
– Achieving rapid hemodynamic improvement and diuresis while maintaining renal function
– Reducing the need for prolonged hospitalization due to electrolyte imbalances or renal dysfunction
– Reducing the likelihood of readmission, especially within 30 days (non-reimburseable)
ADDRESSING AN UNMET CLINICAL NEED:
Natriuretic Peptides in Chronic Decompensated
Heart Failure
Stages ofCHF
ACC/AHAGuidelines
2001
AHigh-risk patients:
HTN, DM, CAD, + FH, LBBB, cardiotoxic drugs
BStructural heart disease, asymptomatic:
LVH, MI, low LVEF, dilatation, valvular disease
CStructural heart disease,
prior or current symptoms
DRefractory
symptoms rest + hospitalizations
Renin-Angiotensin-AldosteroneEndothelin
Catecholamines
Natriuretic Peptides
VasoconstrictionSodium/Fluid Retention
Chronic Cardiac Stress → Tissue Remodeling/Fibrosis
VasodilationNatriuresis/Diuresis↓ Cardiac Stress↓ Remodeling
Opposition of Neurohormonal Forces in HF
FUSION Study Design
n = 69n = 69
n = 72n = 72
n = 69n = 69 Nesiritide 0.01 Nesiritide 0.01 µµg/kg/ming/kg/min, following bolus, following bolus–– Inotropes not permittedInotropes not permitted
Nesiritide 0.005 Nesiritide 0.005 µµg/kg/ming/kg/min, following bolus, following bolus–– Inotropes not permittedInotropes not permitted
Standard CareStandard Care –– Inotropes permittedInotropes permitted
--3030 to to --5 5 days post days post hospital hospital dischargedischarge
Weekly Outpatient VisitsWeekly Outpatient Visits
n = 210n = 210
4 Weeks4 Weeks
ScreeningScreening
12 Weeks12 Weeks
FollowFollow--upup
Standard Care vs. Nesiritide (0.005) P=0.019Standard Care vs. Nesiritide (0.01) P=0.269Standard Care vs. All Nesiritide P=0.034
Standard Care (n = 23)Nesiritide (0.005) (n = 24)Nesiritide (0.01) (n = 20)All Nesiritide (n = 44)
FUSION I Improvement in Left Ventricular Systolic Function
*compared to standard care
0.090.030.44N/AP-value*
4.6 +/- 4.25.3 +/- 5.04.0 +/- 3.33.2 +/- 3.8Change at 12 Weeks
28.25 +/- 14.837.7 +/- 13.828.8 +/- 15.829.6 +/- 18.6EF at Baseline
All Patients(n = 77)
Nesiritide 0.01 Dose
(n = 37)
Nesiritide 0.005 Dose
(n = 40)
Standard Care
(n = 38)
Summary
• Outpatient nesiritide can be safely administered and is well tolerated as adjunctive therapy for chronic decompensated HF
• Subjects on nesiritide were alive and out of hospital longer vs. standard care
• Mortality/hospitalization was better in the high-risk group treated with nesiritide, P<0.05
• Neurohormonal and echo data suggest a favorable influence on remodeling as a potential mechanism of benefit
• A theoretical biological hypothesis suggests that BNP exerts a negative influence on growth and fibrosis
• FUSION pilot supports further clinical trials
Decompensated Heart Failure:
Focusing on Early and Aggressive Treatment to
Improve Patient and Economic Outcomes
Clyde W. Yancy, M.D.University of Texas Southwestern Medical Center
Dallas
Question From Live Broadcast