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NT-proBNP stratified follow up in outpatients heart failure clinics : A Randomized Danish Multicenter Study. NorthStar :. Morten Schou, MD, PhD Principal Investigator Hillerod University Hospital, Copenhagen The Danish Heart Failure Clinics Network
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NT-proBNPstratifiedfollow up in outpatientsheartfailureclinics: A Randomized Danish Multicenter Study NorthStar: Morten Schou, MD, PhD Principal Investigator HillerodUniversity Hospital, Copenhagen The Danish Heart FailureClinics Network Onbehalfon the NorthStarSteering Group: Finn Gustafsson, Lars Videbaek, Per R Hildebrandt and Morten Schou
Roche Diagnostics International, Basel, Schwitzerland • Research grant • Roche Diagnostics, Copenhagen, Denmark • Research grant • Merck, Sharp and Dohme, Copenhagen, Denmark • Research grant Disclosures:
Objectives: • To determine the effectiveness of a continued • heart failure clinic intervention. • To determinewhetherNT-proBNPcouldidentify patients • withparticularbenefit of continuedfollow up. • Population: • Predefinedclinical stable systolicheartfailure patients • on optimal medicaltherapy. • Primaryoutcome: • Time to deathor a CV hospitalization NorthStar:
GP Echo Lab Dept of Cardiology/ InternalMedicine • Heart failureclinic (HFC): • Education • Exercise • Etiologi • ACE-I/ARB´s • BB • Aldosterone antagonists • Adjustingdoses of diuretics • CRT and/or ICD The Danish Heart Failure Clinic Program: • ScientificQuestion: • Whereshouldthese • patients befollowed ? • HFC ? • GP (routine in DK) ? • Onlyhighrisk • patients in the HFC ? • e.gidentified by NT- • proBNP ? Considered Stable Remain symptomatic HTX ? LVAD ? (2 centers)
In the NorthStarStudy the patients wereon optimal therapybefore • randomization and onlylittleroomwasleft for a loweringstrategy. • (EMPHASIS , REVERSE and MADIT-CRT wereinitiatedbeforeNorthStar) NT-proBNPmonitoring ? • We, therefore, created a clinicalchecklist, whichshouldbeused • ifNT-proBNPincreased > 30 % compared to the randomization visit • even the patient did not become more symptomatic.
Clinically stable systolic heart failure patients on optimal • medical therapy benefit from long term follow up in a HFC. • The benefit is driven by an effect only in high risk patients • identified by NT-proBNP > 1000 pg/ml. (prespecified interaction analysis) • High risk patients identified by NT-proBNP > 1000 pg/ml • benefit further from NT-proBNP monitoring. Hypotheses:
PROBE design • (ProspectiveRandomizedOpen-labeledBlindedEndpoint) • Multicenter (18 sites) • InvestigatorInitiated Study design:
The NorthStar Intervention(Organizational): The patients visit the HFC with 1-3 months intervals basedon the investigatorsdiscretion
CheclistifNT-proBNPincreased > 30 %: M. Schou et al. (NorthStarDesignPaper): AHJ 2008
Randomization: M. Schou et al. (NorthStarDesignPaper): AHJ 2008 • Simple randomizationwith strata* • (*due to the prespecifiedinteractionanalysis (NT-proBNP*HFC))
N = 6180 patients had at leastone visit in one of the HFC in the randomizationperiod (registry) Registry N= 1628 patients consideredeligible Enrollment N = 508 excluded N = 1120 patients randomized TrialStructure: Allocation N = 460 patients allocated to GP N= 660 patients allocated to HFC (N=461) orHFC+NT-proBNP (N=199) Lost to follow up (N=0) Informedconsentwithdrawn due to traffiicaccident (N=1) Follow up Lost to follow up (N=0) N= 460 patients included in final analyses N=659 patients included in final analyses Analysis
Patients Characteristics:Heart failureClinicvGeneral Practice
Patients Characteristics:Heart failureClinic(Usualcare)vHeart FailureClinic(NT-proBNPmonitoring) * Only patients withNT-proBNP > 1000 pg/ml
PrimaryCompositeEndpoint:Heart failureClinicvGeneral Practice
Events: 159 Events: 177 PrimaryCompositeEndpoint(Time to mortalityor a CV hospitalization): Blue: GP (N=460) HFC: Black (N=461) HR: 1.17, 95 % CI : 0.45-1.45, P = 0.145
NT-proBNPstratifiedhypothesis: HR: 0.94; 95 CI:0.69-1.27; P = 0.680 Blue: GP (N= 257 and N= 203) HFC: Black (N=253 and N=208) HFC*NT-proBNP > 1000 pg/ml; P = 0.721 (test for heterogeneity)
PrimarycompositeEndpoint:Heart failureClinic(Usualcare)vHeart FailureClinic(NT-proBNPmonitoring) * Only patients withNT-proBNP > 1000 pg/ml
PrimaryCompositeEndpoint: HFC (N=208) Usualcare: Black HFC (N=199) NT-proBNP: Red HR: 0.94; 95 CI:0.69-1.27; P = 0.680 HR: 0.95, 95 % CI: 0.71-1.1.29, P = 0.776
Time to death • Time to a cardiovascularhospitalization • Time to a heartfailurehospitalization • Time to an over all-hospitalization • Minnesota Livingwith Heart Failure Score • NYHA class • NT-proBNP • Patients admitted, admissions and admission days • P > 0.05 for all: • HFC vs. GP • NT-proBNPstratifiedhypothesis • HFC vsHFC+NT-proBNP SecondaryEndpoints:
Clinically stable systolicheartfailure patients on optimal • medicaltherapy do not benefit from long term follow up in • a HFC. • A subgroup of high-risk patients identified by NT-proBNP • do not benefit from long term follow up in a HFC. • The present NT-proBNPmonitoringconceptdoes not • improve long term clinicaloutcome. Conclusions:
Clinically stable HF patients canbereferred back to their • GP. • Adherence in GP wassuprisinglygood – wronghypothesis ? • NT-proBNPidentified the high-risk patients and did it´s job, but our • intervention(s) could not improveoutcome for thesepatients – • wrongconcept(s) ? • We did not power the study to look at HF hospitalizations– wrong • endpoint ? • Our patients wereprimarily NYHA class I-II – willNT-proBNP • monitoringonlywork in NYHA class III-IV – wrong patients ? • Type II error - Bad luck ? Interpretation:
