CC oordinating study oordinating study evaluating evaluating OO utcomes of utcomes of AA dvising and dvising and CC ounseling in ounseling in HH eart failure eart failureTiny Jaarsma RN PhD, Dirk J van Veldhuisen MD PhD

University Medical Center Groningen, the Netherlands

on behalf of the COACH investigators

Funded by the Netherlands Heart Foundation:

Program grant 2000Z003

Unrestricted grants from Novartis, Biosite and Roche

Objective COACH main studyObjective COACH main study

To determine the effect of 2 levels of intensity To determine the effect of 2 levels of intensity in nurse-led heart failure care compared to a in nurse-led heart failure care compared to a control group in an adequately powered studycontrol group in an adequately powered study

To study underlying mechanisms of heart To study underlying mechanisms of heart failure disease management programsfailure disease management programs

Jaarsma et al. Eur J Heart Fail 2004

Objective subgroup analyses Objective subgroup analyses

To determine possible heterogeneity in the To determine possible heterogeneity in the effect nurse-led heart failure care with regard effect nurse-led heart failure care with regard to prespecified baseline variablesto prespecified baseline variables

Basic Nurse led Advising + Counseling

Intensive Nurse led Advising + Counseling

Control (cardiologist only)

R

Hospital admission

18 months

COACH - methods: DesignCOACH - methods: Design

Discharge

Jaarsma et al. Eur J Heart Fail 2004

COACH - methodsCOACH - methodsIntervention contacts in 18 Intervention contacts in 18 monthsmonths

4 4 4

9

18

2

2

Control Basic A&C Intensive A&C

Nu

mb

er

of

con

tact

s

Visits to cardiologist

Visits to HF nurse

Home visit

Multidisciplinary advice

Inclusion and exclusion criteriaInclusion and exclusion criteria

InclusionInclusion

- Hospital admission for symptomatic CHF (NYHA II-IV)Hospital admission for symptomatic CHF (NYHA II-IV)

- Evidence of structural underlying heart disease Evidence of structural underlying heart disease

- Age > 18 yearsAge > 18 years

ExclusionExclusion

- Participating in other research trials Participating in other research trials

- Invasive intervention previous 6 months/planned in 3 Invasive intervention previous 6 months/planned in 3 monthsmonths

- Evaluation for heart transplantationEvaluation for heart transplantation

Major Endpoints Major Endpoints

Primary endpointPrimary endpoint

– Time to first event (all cause mortality + HF Time to first event (all cause mortality + HF readmission)readmission)

– Number of unfavorable days (number of days in Number of unfavorable days (number of days in hospital or dead) hospital or dead)

Major Secondary endpointsMajor Secondary endpoints

– Individual components of primary endpointIndividual components of primary endpoint All cause mortalityAll cause mortality HF readmissionHF readmission

Statistical analysisStatistical analysis

Primary endpointsPrimary endpoints- Two-sided log-rank test (Kaplan Meyer curves)Two-sided log-rank test (Kaplan Meyer curves)- Mann-Whitney-U testsMann-Whitney-U tests

InteractionInteraction- Interaction tests for endpoints using baseline Interaction tests for endpoints using baseline

demographics (treatment x subgroup demographics (treatment x subgroup interaction)interaction)

- Cox proportional hazards models Cox proportional hazards models

Subgroups

- Baseline demographic and clinical variablesBaseline demographic and clinical variables

Results: Baseline Results: Baseline

TotalTotal

N=1,023N=1,023ControlControl

N=339N=339Basic Basic A&CA&C

N=340N=340

Intensive Intensive A&CA&C

N=344N=344

Age (yrs)Age (yrs)

Female gender Female gender 7171

38%38%7272

40%40%7171

34%34%7070

39%39%

NYHA II at dischargeNYHA II at discharge

NYHA III/IV at dischargeNYHA III/IV at discharge50%50%

50%50%54%54%

46%46%50%50%

50%50%52%52%

52%52%

LVEF (%)LVEF (%)

≤≤ 40%40%

>40% >40%

3434

73%73%

27%27%

3434

70%70%

30%30%

3434

72%72%

28%28%

3333

75%75%

25%25%

Medication at dischargeMedication at discharge- ACE/AIIACE/AII- B-BlockerB-Blocker- Diuretics Diuretics

83%83%

66%66%

95%95%

82%82%

65%65%

96%96%

85%85%

70%70%

97%97%

81%81%

63%63%

95%95%

BNP (pg/ml) BNP (pg/ml) 493493 535535 478478 479479

Depressive symptomsDepressive symptoms 39%39% 37%37% 39%39% 42%42%

Extra contacts Extra contacts

858

5,868

2,347

Control Basic A&C Intensive A&C

Num

ber

of co

nta

cts

+

+

+

+ 33%

+ 40%

+ 10%

Primary endpoint: All cause mortality and HF readmission

Months

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

All

cau

se m

ort

alit

y o

rH

F r

ea

dm

issi

on

(%

)

0

10

20

30

40

50

Control Basic A&CIntensive A&C

Control vs Basic A&CHazard ratio 0.96 (95% CI 0.76–1.21), p=0.73

Control vs Intensive A&CHazard ratio 0.93 (95% CI 0.73–1.17), p=0.52

0

10000

20000

30000

40000

6 months 12 months 18 months

Num

ber

of

unfa

vora

ble

days

ControlBasic A&CIntensive A&C

Co-primary endpoint: Unfavorable days

6,229 days = 15% decrease, ns

40,000

30,000

20,000

10,000

Secondary endpoint:All cause mortality

Months

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Pro

po

rtio

n o

f a

ll ca

use

mo

rta

lity

(%)

0

5

10

15

20

25

30

35

ControlBasic A&CIntensive A&C

Control vs Intensive A&CHazard ratio 0.81 (95% CI 0.60–1.08), p=0.15

Control vs Basic A&CHazard ratio 0.88 (95% CI 0.66–1.18), p=0.39

Control vs combined Basic and Intensive A&CHazard ratio 0.85 (95% CI 0.66–1.08), p=0.18

Secondary endpoint:HF readmission

Months

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

HF

rea

dm

issi

on (

%)

0

5

10

15

20

25

30

35

ControlBasic A&CIntensive A&C

Control vs Basic A&CHazard ratio 0.98 (95% CI 0.72–1.32), p=0.89

Control vs Intensive A&CHazard ratio 1.08 (95% CI 0.81–1.46), p=0.60

MaleFemale

DepressedNot depressed

Subgroup analysis:Subgroup analysis: Primary endpointPrimary endpoint

Age >65Age ≤ 65

BNP ≤ 500 pg/mlpg/mlBNP > 500 pg/mlpg/ml

NYHA IINYHA III/IV

LVEF ≤ 40 LVEF > 40

0.27

0.58

0.05

0.52

0.80

0.43

P value for interaction

Favors intervention

Favors control

Hazard Ratio

Male

Female

DepressedNot depressed

Subgroup analysis:Subgroup analysis: MortalityMortality

Age >65Age ≤ 65

BNP ≤ 500 pg/mlpg/mlBNP > 500 pg/mlpg/ml

NYHA IINYHA III/IV

LVEF ≤ 40 LVEF > 40

0.65

0.85

0.01

0.10

0.25

0.37

P value for interaction

Favors intervention

Favors control

Hazard Ratio

Conclusion subgroup analysisConclusion subgroup analysis

No significant treatment x subgroup No significant treatment x subgroup interaction was found except for an interaction was found except for an interaction between depression and all cause interaction between depression and all cause mortality mortality

The power to analyses each subgroup was The power to analyses each subgroup was limited limited

Conclusion (2)Conclusion (2)

Nurse-led education and counseling independent of Nurse-led education and counseling independent of intensity (on top of treatment by a cardiologist) did not intensity (on top of treatment by a cardiologist) did not reduce the combined endpoint of time to HF reduce the combined endpoint of time to HF hospitalization or death in an unselected HF hospitalization or death in an unselected HF population.population.

Nurse-led advising and counseling is associated with a Nurse-led advising and counseling is associated with a relevant but statistically not significant 15% decrease relevant but statistically not significant 15% decrease of unfavorable days, driven by a 15% (ns) decrease in of unfavorable days, driven by a 15% (ns) decrease in all cause mortality but not in hospitalizations.all cause mortality but not in hospitalizations.

ImplicationsImplications

Close intensive nurse-led advising and Close intensive nurse-led advising and counseling in chronic heart failure patients counseling in chronic heart failure patients might decrease mortality at the ‘cost’ of might decrease mortality at the ‘cost’ of more – shorter – hospitalizationsmore – shorter – hospitalizations

No clear subgroups x treatment interaction No clear subgroups x treatment interaction was found, suggesting that further studies to was found, suggesting that further studies to determine the most optimal model for heart determine the most optimal model for heart failure disease management are neededfailure disease management are needed

Steering committeeSteering committee Prof. Dr. D.J. van Veldhuisen Prof. Dr. D.J. van Veldhuisen Dr. T. Jaarsma Dr. T. Jaarsma    Dr. P.H.J.M. Dunselman Dr. P.H.J.M. Dunselman Prof. Dr. W.H. van GilstProf. Dr. W.H. van Gilst Dr. H.L. HillegeDr. H.L. Hillege Prof. Dr. A.W. Hoes Prof. Dr. A.W. Hoes Prof. Dr. K.I. LieProf. Dr. K.I. Lie D.J.A. Lok D.J.A. Lok Prof. Dr. R. Sanderman Prof. Dr. R. Sanderman Prof. Dr. J.G.P. Tijssen Prof. Dr. J.G.P. Tijssen Dr. M.C.M. SentenDr. M.C.M. Senten I. KamerlingI. Kamerling

Endpoint adjudication committeeEndpoint adjudication committee Dr. C.M.H.B. Lucas (chair) Dr. C.M.H.B. Lucas (chair) Dr. J.H. CornelDr. J.H. Cornel Dr. R.W.M.M. JansenDr. R.W.M.M. Jansen Dr. F.H. RuttenDr. F.H. Rutten Dr. F. van den Berg Dr. F. van den Berg

Safety analysis Safety analysis Prof. Dr. J.J.V. McMurray, Glasgow, UK.Prof. Dr. J.J.V. McMurray, Glasgow, UK.

ResearchersResearchersDr. M.H.L. van der WalDr. M.H.L. van der WalDr. M.L.A. Luttik Dr. M.L.A. Luttik Dr. J. HogenhuisDr. J. HogenhuisI. LesmanI. Lesman

Investigators and HF nursesInvestigators and HF nurses

University Medical Center Groningen: University Medical Center Groningen: D. J. van Veldhuisen, A.A. Voors, A. Koops, A. D. J. van Veldhuisen, A.A. Voors, A. Koops, A. Klungel, K. van Dijk, G. Westra, Klungel, K. van Dijk, G. Westra,

University Medical Center Amsterdam: University Medical Center Amsterdam: W. Kok, L.M. Konst, J. van der Sloot, T. Veelenturf, W. Kok, L.M. Konst, J. van der Sloot, T. Veelenturf, R. Zwart, S. de Vries, R. Zwart, S. de Vries,

University Medical Center St. Radboud, Nijmegen: University Medical Center St. Radboud, Nijmegen: F. Verheugt, L. Bellersen, L. Knubben, F. Verheugt, L. Bellersen, L. Knubben, L. Baltussen, L. Baltussen,

Medical Center Leeuwarden: Medical Center Leeuwarden: C.J. de Vries, R. Breedveld, A. Obbema, A. Rijenga, D. van der C.J. de Vries, R. Breedveld, A. Obbema, A. Rijenga, D. van der Woude, J. de Bruin, Woude, J. de Bruin,

Twenteborg Hospital, Almelo: Twenteborg Hospital, Almelo: G.C.M Linssen, E. Rodijk, M. Samsen, B. Beverdam, L. G.C.M Linssen, E. Rodijk, M. Samsen, B. Beverdam, L. Bogemann, Bogemann,

Atrium Medical Center Heerlen: Atrium Medical Center Heerlen: J.A. Kragten, T. Thuis, I. Kremer, V. Post, S. Jongen, J.A. Kragten, T. Thuis, I. Kremer, V. Post, S. Jongen, Jeroen Bosch Hospital Den Bosch: Jeroen Bosch Hospital Den Bosch: M.C.G. Daniëls, D. Jaftoran, V. van Zonsbeek, A. M.C.G. Daniëls, D. Jaftoran, V. van Zonsbeek, A.

Berkhout, Berkhout, Rijnstate Hospital, ArnhemRijnstate Hospital, Arnhem: F.F. Willems, M. Rolfes, P. Nienaber, : F.F. Willems, M. Rolfes, P. Nienaber, Amphia Hospital,, BredaAmphia Hospital,, Breda P.H.J.M. Dunselman, N. Creemer, I. Lauwerijssen, C. Paes, P.H.J.M. Dunselman, N. Creemer, I. Lauwerijssen, C. Paes, Refaja Hospital, Stadskanaal: Refaja Hospital, Stadskanaal: L. van Wijk, K. de Vries, D. Thoma, R. Niewold, M. Wijbenga, L. van Wijk, K. de Vries, D. Thoma, R. Niewold, M. Wijbenga, Tweesteden Hospital,, TilburgTweesteden Hospital,, Tilburg: J. Widdershoven E. Hendriks, H. Broers, : J. Widdershoven E. Hendriks, H. Broers, Streekziekenhuis Midden Twente, Hengelo: Streekziekenhuis Midden Twente, Hengelo: A. Derks, L. Odink, P. ter Horst, W. Wolters, L. A. Derks, L. Odink, P. ter Horst, W. Wolters, L.

Navis, Navis, Scheper Hospital, EmmenScheper Hospital, Emmen: M.J. Nagelsmit , A. Bakker, W. Veenstra, J.W. van Brakel, : M.J. Nagelsmit , A. Bakker, W. Veenstra, J.W. van Brakel, Medisch Spectrum Twente, Enschede: Medisch Spectrum Twente, Enschede: P. van der Burgh, J. Roukema, H. Glazenburg, J. P. van der Burgh, J. Roukema, H. Glazenburg, J.

Grooters, Grooters, Wilhelmina Hospital Assen:Wilhelmina Hospital Assen: M.L. Pentinga, R. Aardema, J. Veninga, M.L. Pentinga, R. Aardema, J. Veninga, Deventer Hospital, Deventer: Deventer Hospital, Deventer: D.J.A. LokD.J.A. Lok J. Burger, D. Pruijsers, J. Burger, D. Pruijsers, Oosterschelde Ziekenhuis, GoesOosterschelde Ziekenhuis, Goes: A.H. Liem , J. Witkam, A. Roelse, E. Salawanei: A.H. Liem , J. Witkam, A. Roelse, E. Salawanei