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