Evolving Patterns Of Use Of Aldosterone Inhibition In Chronic Heart Failure; A

Report From Get With The Guidelines HF

Nancy M. Albert, Clyde W. Yancy,

Li Liang,Adrian Hernandez,Gregg C. Fonarow,

and the Get with the Guidelines Steering Committee and Hospitals

Presenter Disclosure Presenter Disclosure InformationInformation

AHA Scientific SessionsAHA Scientific SessionsEvolving Patterns Of Use Of Aldosterone

Inhibition In Chronic Heart Failure; A Report From Get With The Guidelines HF

I will not discuss off label or investigational use of drugs or devices in my presentation.

I have financial relationships to disclose: Consultant and Speakers Bureau:

GlaxoSmithKline Consultant: Medtronic

GWTG-HF was sponsored in part by funding from GlaxoSmithKline to the American Heart

Association

Background: Level B Evidence

Aldosterone inhibition recommendations: Moderately severe-severe HF

symptoms (i.e. hospitalized for HF) and Reduced LVEF Careful monitoring to preserve renal

function and normal K+ Serum creatinine

≤ 2.5 mg/dL- men ≤ 2.0 mg/dL – women

Serum potassium < 5.0 mEq/L

Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

Background: Utilization Of Aldosterone Inhibitors

83.0 83.0

65.4

39.2

18.0

52.3

0

20

40

60

80

100

Eli

gib

le P

atie

nts

Tre

ate

d (

%)

OPTIMIZE-HF: Hospital Discharge

ACEI/ARB, -blocker, and aldosterone antagonist use in eligible patients with LVSD; statin in HF patients with a history of CAD, PVD, CVD and/or diabetes; and warfarin use in patients with HF and atrial fibrillation.

Fonarow et al. JAMA 2007;297:61-70.

-Blocker at Discharge

(13,032/15,675)

Evidence-Based -Blocker

(10,248/15,675)

ACEI/ARB at Discharge

(11,976/14,493)

Aldosterone Antagonist

(3,621/20,118)

Statin (14,904/38,066)

Warfarin (6,571/12,560)

83 83

65.4

18

39.2

52.3

Background: Utilization Of Aldosterone Inhibitors

51

39

8086

36

6961

0

10

20

30

40

50

60

70

80

90

100

ACEI / ARB Beta-Blocker AldosteroneAntagonist

Anticoagulationfor Atrial

Fibrillation

CRT (CRT-D / CRT-P)

ICD / CRT-D HF Education

Pat

ien

ts (

%)

(N = 11,271 / 14,167)

(N = 12,039 / 14,058) (N = 905 / 2505)

(N = 2450 / 3533)(N = 528 / 1361)

(N = 3630 / 7169) (N = 9459 / 15,381)

IMPROVE-HF: Cardiology Outpatient Practices at Baseline

Fonarow GC, et al. Circ Heart Fail. 2008;1:98–106.

Background: Potential for Harm

Usage since RALES1 > 7 fold : 3% to 21.3%1

> 4 fold : 34/1000 pts. (94) to 149/1000 pts (01) 30.9% did not meet enrollment criteria1

22.8%, hyperkalemia; 14.1% Sr. Creatinine ≥ 2.5 mg/dL; 17.3%, eGFR < 30 ml/min

Discontinued in 7.2% (67/926 cases)3

49%, hyperkalemia; 51%, renal failure Hospitalization for hyperkalemia2

2.4/1000 (1994) to 11.0/1000 (2001) Mortality for hyperkalemia2

0.3/1000 (1994) to 2.0/1000 (2001)

1Masoudi FA, et al. Circulation 2005;112:39-47.2 Juurlink DN, et al. NEJM 2004;351:543-551. 3Tamirisa KP et al. Am Heart J 2004;148:971-978.

PURPOSE Problem:

It is unknown if HF patients in a quality of care hospital program receive aldosterone inhibitors more often and receive this therapy per recommendations

Research Question: Has the appropriateness of

aldosterone inhibitor usage among patients hospitalized for heart failure improved since 2005?

METHODS: Sample

Get With the Guidelines-Heart Failure (GWTG-HF) National initiative of the AHA to

improve guidelines adherence in patients hospitalized with HF

Study Cohort 242 participating hospitals 45,322 patients hospitalized for HF

Discharged home Without contraindications to aldosterone

inh. January 1, 2005 – December 26, 2007

Patient Management Tool

Data was recorded using the Patient Management Tool™ (Outcome, Cambridge, MA), a Web-based interactive assessment and reporting system that tracks treatment and facilitates evidence- based medicine

METHODS: Definitions & Analysis

Definitions LV systolic dysfunction: EF ≤ 35% Normal K+ level: ≤ 5.5 mmol/L Normal serum creatinine: < 2.5 mg/dL Opt Medical Tx: BB, ACEi/ARB or diuretic if

indicatedAnalysis

Cochran-Mantel Haenzel general association statistics: Aldosterone in patient groups

Cochran-Mantel Haenzel- Row Mean scores: Aldosterone and time Within hospital clustering was considered

Multivariable logistic regression analysis using Generalized Estimating Equations to account for pt & hosp characteristics and clustering within hospitals

RESULTS: Pt. Characteristics

Total N

No Aldo Inh.

Yes Aldo Inh. P value

Age, years; mean 70.2 71.1 66.4 <0.0001

Gender, male; % 51.5 50.7 57.7 <0.0001

Race, Caucasian; % 68.0 68.8 64.4 <0.0001

Hypertension; % 70.8 71.4 68.6 <0.0001

Prior MI, % 13.7 13.1 16.2 <0.0001

Smoking Hx, % 80.8 81.6 77.2 <0.0001

Renal Insuff. (SCr > 2.0) 16.4 17.1 13.5 <0.0001

Non-Ischemic HF 47.8 47.7 47.9 <0.0001

RESULTS: Pt. Characteristics

Status: Mean valuesTotal

N

No Aldo Inh.

Yes Aldo Inh. P value

Adm. SBP, mmHg 141.7 143.6 133.6 <0.0001

Adm. HR, bpm 85.0 84.8 86.0 <0.0001

Adm. BNP, pg/mL 1306 1275 1434 <0.0001

Adm. Sr Creat., mg/dL 1.86 1.94 1.52 <0.0001

Adm. BUN, mg/dL 28.5 29.0 26.7 <0.0001

Ejection Fraction, % 38.41 40.41 30.02 <0.0001

RESULTS: Pt. Characteristics

Therapies; Mean valuesTotal

N

No Aldo Inh.

Yes Aldo Inh. P value

Disch home after education x 6 instructions

81.8 80.2 85.7 <0.0001

Disch LVSD + ACEi/ARB Tx 87.6 86.2 91.1 <0.0001Disch LVSD + BB Tx 89.6 88.4 92.8 <0.0001Disch Smoking cessation 91.5 90.7 94.2 <0.0001ICD, % 10.4 8.3 19.6 <0.0001CRT/ICD, % 9.3 8.5 12.9 <0.0001Dialysis, % 3.7 4.5 0.5 <0.0001

RESULTS: Aldosterone Inh. Use

Use of Aldosterone Inhibitor %Overall 18.9EF ≤ 35% 28.9LVSD + Sr Creat < 2.5 mg/dL 31.8LVSD + Cr Clearance > 30 ml min 32.6LVSD + Sr K+ ≤ 5.5 mmol/L 30.5LVSD + optimal medical Tx when not contraindicated

29.4

ACC/AHA guidelines (EF ≤ 35%) 33.8

RESULTS: Aldosterone Inh. Use

Over Time

Group

Aldo Inh. Use

Trends in Aldosterone Inhibitor Use Over Time

P value*

Jan-Jun 05

Jul-Dec 05

Jan-Jun 06

Jul-Dec 06

Jan-Jun 07

Jul-Dec 07

Overall Use 8,564 17.25 18.90 19.36 20.23 17.70 19.09 <.0001

LVSD 5,735 25.3 28.34 29.58 31.08 27.49 29.53 <.0001

No LVSD 2,050 9.68 11.10 11.45 11.60 9.64 10.44 .140

Core HF drugs 5,619 25.61 28.85 30.12 31.54 28.03 29.89 <.0001

Class I guideline criteria

3,687 29.62 33.95 33.44 36.03 32.93 .0004

*, adjusted for within-hospital clustering

RESULTS: Trends in Compliance of Aldosterone Inhibitor Use Over Time

Aldosterone Inh. Users (n / N)

Trends in COMPLIANCE of Aldosterone Inhibitor Use Over Time

P value*

Jan-Jun 05

Jul-Dec 05

Jan-Jun 06

Jul-Dec 06

Jan-Jun 07

Jul-Dec 07

S.Cr < 2.5 mg/dl (5149 / 5388)

93.78 95.37 96.81 95.47 94.70 96.29 .88

CrCl > 30 ml/m (4580 / 5077)

88.40 88.44 90.45 90.64 91.03 90.70 .88

K+ ≤ 5.5 mEq/L (4509 / 4523)

100.0 99.72 99.89 99.52 99.67 99.49 .11

*, adjusted for within-hospital clustering

Multivariable ModelingLogistic regression with GEE approach Excluded cases with missing data. N=13,289 (67% of LVSD population) Aldosterone use = 30.7%

VariableAdjuste

d ORLower 95% CI

Upper 95% CI

P value

Age per 10 years 0.85 0.82 0.88 <0.0001

SBP per 10 units 0.90 0.89 0.92 <0.0001

Hx ICD 1.52 1.37 1.68 <0.0001

Hx Chronic dialysis

0.16 0.08 0.32 <0.0001

Adm. Sr Creat <2.5

2.22 1.81 2.73 <0.0001

Optimal Medical Tx

2.35 1.64 3.38 <0.0001

LIMITATIONS Data presented are dependent upon the

accuracy and completeness of data abstraction from medical chart review

GWTG-HF hospitals are self selected

Rationale for decisions regarding therapy utilization may not be captured

These findings may not apply to practices that differ in patient characteristics or care patterns from GWTG-HF hospitals

CONCLUSIONS These data are among the first to assess

aldosterone inhibitor use in hospitalized patients and appropriateness since ~ 2005.

Within pts enrolled in GWTG HF, they demonstrate: Appropriate use of aldosterone inhibitors

increased modestly from 2005-2007 Non-indicated use was low Overall use of aldosterone inhibitors remains

lower than expected Users are more likely to have higher compliance

on other performance and quality measures Additional research is required to identify ongoing

impediments to aldosterone inhibitors use.