C oordinating study evaluating O utcomes of A dvising and C ounseling in H eart failure

1. C oordinating study evaluating O utcomes of A dvising and C ounseling in H eart failure Tiny Jaarsma RN PhD, Dirk J van Veldhuisen MD PhD University Medical Center Groningen, the Netherlands on behalf of the COACH investigators

2. Funded by the Netherlands Heart Foundation: Program grant 2000Z003 Unrestricted grants from Novartis, Biosite and Roche

3. Objective COACH main study To determine the effect of 2 levels of intensity in nurse-led heart failure care compared to a control group in an adequately powered study To study underlying mechanisms of heart failure disease management programs Jaarsma et al. Eur J Heart Fail 2004

4. Objective subgroup analyses To determine possible heterogeneity in the effect nurse-led heart failure care with regard to prespecified baseline variables

5. COACH - methods: Design Control (cardiologist only) Basic Nurse led Advising + Counseling R Intensive Nurse led Advising + Counseling 18 months Hospital admission Discharge Jaarsma et al. Eur J Heart Fail 2004

6. COACH - methodsIntervention contacts in 18 months Multidisciplinary advice Home visit Visits to HF nurse Visits to cardiologist

7. Inclusion and exclusion criteria Inclusion Hospital admission for symptomatic CHF (NYHA II-IV) Evidence of structural underlying heart disease Age > 18 years Exclusion Participating in other research trials Invasive intervention previous 6 months/planned in 3 months Evaluation for heart transplantation

8. Major Endpoints Primary endpoint • Time to first event (all cause mortality + HF readmission) • Number of unfavorable days (number of days in hospital or dead) Major Secondary endpoints • Individual components of primary endpoint • All cause mortality • HF readmission

9. Statistical analysis Primary endpoints • Two-sided log-rank test (Kaplan Meyer curves) • Mann-Whitney-U tests Interaction • Interaction tests for endpoints using baseline demographics (treatment x subgroup interaction) • Cox proportional hazards models Subgroups • Baseline demographic and clinical variables

10. Results: Baseline

11. Extra contacts + 10% + + 40% + 33% + +

12. Primary endpoint: All cause mortality and HF readmission

13. Co-primary endpoint: Unfavorable days 40,000 6,229 days = 15% decrease, ns 30,000 20,000 10,000

14. Secondary endpoint: All cause mortality

15. Secondary endpoint: HF readmission

16. Subgroup analysis:Primary endpoint P value for interaction Male Female 0.27 Age >65 Age ≤ 65 0.58 Depressed Not depressed 0.05 LVEF ≤40 LVEF > 40 0.52 BNP ≤ 500 pg/ml BNP > 500 pg/ml 0.80 NYHA II NYHA III/IV 0.43 Favors intervention Hazard Ratio Favors control

17. Subgroup analysis:Mortality P value for interaction Male Female 0.65 Age >65 Age ≤ 65 0.85 Depressed Not depressed 0.01 LVEF ≤40 LVEF > 40 0.10 BNP ≤ 500 pg/ml BNP > 500 pg/ml 0.25 NYHA II NYHA III/IV 0.37 Favors control Favors intervention Hazard Ratio

18. Conclusion subgroup analysis • No significant treatment x subgroup interaction was found except for an interaction between depression and all cause mortality • The power to analyses each subgroup was limited

19. Conclusion (2) • Nurse-led education and counseling independent of intensity (on top of treatment by a cardiologist) did not reduce the combined endpoint of time to HF hospitalization or death in an unselected HF population. • Nurse-led advising and counseling is associated with a relevant but statistically not significant 15% decrease of unfavorable days, driven by a 15% (ns) decrease in all cause mortality but not in hospitalizations.

20. Implications • Close intensive nurse-led advising and counseling in chronic heart failure patients might decrease mortality at the ‘cost’ of more – shorter – hospitalizations • No clear subgroups x treatment interaction was found, suggesting that further studies to determine the most optimal model for heart failure disease management are needed

21. Researchers Dr. M.H.L. van der Wal Dr. M.L.A. Luttik Dr. J. Hogenhuis I. Lesman Steering committee • Prof. Dr. D.J. van Veldhuisen • Dr. T. Jaarsma • Dr. P.H.J.M. Dunselman • Prof. Dr. W.H. van Gilst • Dr. H.L. Hillege • Prof. Dr. A.W. Hoes • Prof. Dr. K.I. Lie • D.J.A. Lok • Prof. Dr. R. Sanderman • Prof. Dr. J.G.P. Tijssen • Dr. M.C.M. Senten • I. Kamerling Endpoint adjudication committee • Dr. C.M.H.B. Lucas (chair) • Dr. J.H. Cornel • Dr. R.W.M.M. Jansen • Dr. F.H. Rutten • Dr. F. van den Berg Safety analysis • Prof. Dr. J.J.V. McMurray, Glasgow, UK.

22. Investigators and HF nurses University Medical Center Groningen: D. J. van Veldhuisen, A.A. Voors, A. Koops, A. Klungel, K. van Dijk, G. Westra, University Medical Center Amsterdam: W. Kok, L.M. Konst, J. van der Sloot, T. Veelenturf, R. Zwart, S. de Vries, University Medical Center St. Radboud, Nijmegen: F. Verheugt, L. Bellersen, L. Knubben, L. Baltussen, Medical Center Leeuwarden: C.J. de Vries, R. Breedveld, A. Obbema, A. Rijenga, D. van der Woude, J. de Bruin, Twenteborg Hospital, Almelo: G.C.M Linssen, E. Rodijk, M. Samsen, B. Beverdam, L. Bogemann, Atrium Medical Center Heerlen: J.A. Kragten, T. Thuis, I. Kremer, V. Post, S. Jongen, Jeroen Bosch Hospital Den Bosch: M.C.G. Daniëls, D. Jaftoran, V. van Zonsbeek, A. Berkhout, Rijnstate Hospital, Arnhem: F.F. Willems, M. Rolfes, P. Nienaber, Amphia Hospital,, Breda P.H.J.M. Dunselman, N. Creemer, I. Lauwerijssen, C. Paes, Refaja Hospital, Stadskanaal: L. van Wijk, K. de Vries, D. Thoma, R. Niewold, M. Wijbenga, Tweesteden Hospital,, Tilburg: J. Widdershoven E. Hendriks, H. Broers, Streekziekenhuis Midden Twente, Hengelo: A. Derks, L. Odink, P. ter Horst, W. Wolters, L. Navis, Scheper Hospital, Emmen: M.J. Nagelsmit , A. Bakker, W. Veenstra, J.W. van Brakel, Medisch Spectrum Twente, Enschede: P. van der Burgh, J. Roukema, H. Glazenburg, J. Grooters, Wilhelmina Hospital Assen: M.L. Pentinga, R. Aardema, J. Veninga, Deventer Hospital, Deventer: D.J.A. LokJ. Burger, D. Pruijsers, Oosterschelde Ziekenhuis, Goes: A.H. Liem , J. Witkam, A. Roelse, E. Salawanei