Bilan et résultats des grandes études

Transcription

1 Bilan et résultats des grandes études D Klug. Lille Les cardiologues: une population déclinante! Plus de 60 ans Cardiologues 75 ans 25% 84 ans 16 M M Source INSEE

2 Increasing number of ICD implantations. 400 ICD market worldwide (2001 = 100%) MADIT II SCD-HeFT % 0 '01 '02 '03 '04 '05* '06* Year Source: Lehmann Brothers, Sep 2004 * estimate Estimation of the number of patients to follow mortalité 1% mortalité 5% mortalité 10% Hypothèse : nouveaux patients en 2009 Taux d implantations devrait atteindre 250/million d habitants/an d ici 3 à 5 ans Avis de la CEPP du 7 février 2007

3 The device The patient Arrhythmia Clinical status Implantation site The leads Therapies: Appropiate Inappropriate succes Psychological status Vive les remplacements Vive les contrôles de PM

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5 Home Monitoring for Pacemaker Follow-Up: The first prospective randomised trial Principal Investigator: Pr. Philippe MABO CHU Rennes, UniversitéRennes I, Unité Inserm 642, France. COMPAS COMPArative Follow-up Schedule with Home Monitoring Biotronik Home Monitoring Principle Wireless transmission without patient intervention Patient withhome Monitoring implant Cardiomessenger Mobile patient device Data transmission via cellular network BIOTRONIK Service Center Viewdata via internet, , SMS

6 Study Design The study investigates whether Home-Monitoring follow-upofpm patientsis as efficient as conventional method in terms of Significant Serious Adverse Event (SSAE). Enrolment& Randomisation one month after implantation CONTROL Group: patients receiving the standard of care 18 months Mandatory follow-up Conventional follow-up ACTIVE Group: patients followed with Home- Monitoring only Additionalfollow-up triggered by Home-Monitoring or patient Primary end point : SAFETY The study investigates with a non-inferiority hypothesis whether remote monitoring has an impact on the incidence of Serious Adverse Events* (SAE) comprising: Death (all causes) Cardiovascular SAE Device related SAE *SAE are defined as any untoward medical occurrence or any undesirable experience associated with the use of the medical product that results in Death, Hospitalisation, prolongation of an existing hospitalisation, Persistent or significant disability/incapacity

7 Secondary endpoints Analysis of 3 composite criteria of the primary endpoint Reduction of Number of Follow-ups Usefulness of Follow-up Delay of Remote Monitoring to manage adverse events Measurement of the possible impact of HM on quality of life Inclusion Criteria The patient is willing and able to comply with the protocol The patient has provided written informed consent Patient whose medical situation is stable Patient with PHILOS II DR-T Pacemaker one month A/V bipolar lead No change of residence expected during the study

8 Exclusion Criteria Spontaneous Ventricular Rhythm < 30 ppm More than two cardioversionshocks for last 6 months Heart failure not controlled by medical treatment Post myocardial infarction (< 1 month) Post cardiac surgery (< 1 month) Post surgery A/V Arrhythmia A/V Lead dislodgement, or/and impedance, threshold, or sensing failure Pneumothorax/ Hemothorax Infection Automatic Ventricular Threshold Test cannot be realised Participation in another clinical study Enrolment and Randomisation(1:1) BREST SAINT BRIEUC DOUARNENEZ DINAN VANNES CHERBOURG SAINT MALO RENNES NANTES CAEN ANGERS NIORT PESSAC TOURS POITIERS DIEPPE ROUEN AMIENS ORLEANS MONTFERMEIL YERRES EVRY CHATEAUROUX BAR LE DUC SAINT REMY VILLEFRANCHE LYON SAINT ETIENNE LE PUY EN VELAY 43 sites in FRANCE HAGUENAU NANCY COLMAR BESANCON CHAMBERY MONTBELIARD Multicenter, prospective, non inferiority 538 patients enrolled February January 2008 Randomisedclinical trial Private 187 Patients Public 46% 219 Patients 54% ACTIVE CONTROL Group NS Group 269 Patients 269 Patients 50% 50% PAU TOULOUSE SANARY SUR MER TOULON 13 Private Centers 30 Public Centers

9 Patient Population Clinical characteristics similar in both study groups ACTIVE CONTROL Number of patients Age 76±9 77±8 Gender (male) 180 (67%) 170 (63%) EF (%) 59±13 56±12 p=n.s Primary ECG indications ACTIVE Group CONTROL group Other 5% AVB1 11% p=n.s Other 2% AVB1 8% Brady-Tachy or SSS 26% AVB2 26% Brady-Tachy or SSS 27% AVB2 26% BBB 4% AVB3 29% BBB 2% AVB3 34% *BBB=Bundle Branch Block

10 Symptoms before PM implant p=n.s ACTIVE Group (n=258) CONTROL Group (n=255) Aetiology of underlying heart disease p=n.s ACTIVE Group (n=196) CONTROL group (n=182)

11 Class of Treatment at the enrolment Agents acting on the renin-angiotensin system ACTIVE CONTROL Beta blocking agents Calcium channel blockers Antiarrhythmics, class I and III Diuretics Lipid modifying agents Antithrombotic agents Patient without Medication 50% 30% 10% 10% 30% 50% % Patients p=n.s Patients Per Protocole ACTIVE CONTROL TOTAL Patient death (6%) (5%) Drop-out Patient explanted (Patient moves away from 21 3 (1%) (8%) 23 3 (1%) (9%) center, withdrawal of patient consent ) Study termination at 18 PER PROTOCOLE 227 months 248 (83%) (85%)

12 Primary endpoint: Clinical Events Number of patients with more than one major event (deaths, pacemaker dysfunctions and cardiovascular events) ACTIVE CONTROL Number of patients Patients with > 1 SAE 17,3% (43) 19,1% (47) p=n.s Survival Probability for Combined End Points (n=494) 100 Survival (%) CONTROL Group ACTIVE Group Log Rang Test p=0.63 Hazard Ratio : 0.90 (95%CI ) Non inferiority p< Months Kaplan-Meier Method

13 Primary endpoint: Clinical Events Deaths ACTIVE (n=248) CONTROL (n=246) Stroke 0 4 Heart failure 3 0 Cancer 6 3 Non cardiac cause 6 4 Unknown cause 3 2 TOTAL 18 (7,3%) 13 (5,3%) p=ns Primary endpoint: Clinical Events Device related SAE ACTIVE (n=248) CONTROL (n=246) Infection / Extrusion 0 4 Lead dislodgement 0 2 Venous Thrombosis / lead 2 1 High Ventricular Threshold 0 1 TOTAL 2 SAE (1 pt: 0,4%) P=0.03 OR: 0.14 (95%IC: ) 8 SAE (7 pts: 2,8%)

14 Primary endpoint: Clinical Events Cardiovascular SAE ACTIVE (n=248) CONTROL (n=246) Events Patients Events Patients Ventricular arrhythmia Atrial arrhythmia Stroke * Heart failure ** 6 6 Acute Coronary Event Valvular heart disease Pericardial disease Other TOTAL * Including 4 deaths ** Including 3 deaths 37 SAE (29 pts: 11,7%) p=ns 33 SAE (32 pts: 13,0%) Primary endpoint: Clinical Events Cardiovascular SAE ACTIVE (n=248) CONTROL (n=246) Events Patients Events Patients Ventricular arrhythmia Atrial arrhythmia & related stroke 6 Patients 17 Patients p<0.01 OR:0.33 (95%IC ) Heart failure ** 6 6 Acute Coronary Event Valvular heart disease Pericardial disease Other TOTAL 37 SAE (29 pts: 11,7%) 33 SAE (32 pts: 13,0%) * Including 4 deaths ** Including 3 deaths

15 SAE and AE related to Atrial arrhythmias and strokes ACTIVE Group CONTROL Group 6 SAE 21 AE 18 SAE 13 AE % SAE / Total events 22% 58% 6 hospitalisations: 2 AF ablations, 1 cardioversion, 1 hospit with change in medication, 2 strokes Change in medication or reprogrammation: FU triggered by HM (16) or by patient (1) or scheduled at 18-months (4) 18 hospitalisations: 4 AF ablations, 1 cardioversion, 5 hospit with change in medication, 8 strokes (4 deaths) Change in medication or reprogrammation at a scheduled FU Same number of events in both groups but more hospitalisations in the control group Unadjusted hazard ratios for combined end point in different subgroups Characteristics Nb Pts Hazard Ratio (95%IC) All Patients 494 Sex Female 193 Male 301 Age >=80 years 174 <80 years 320 Indication SSS & AF 128 BAV 329 Ejection Fraction >50% 336 <=50% 132 Underlying heart disease Conduct fibrosis 102 Hypertension 65 0,90 (0,60-1,36) 0,92 (0,49-1,73) 0,89 (0,51-1,54) 0,98 (0,46-2,07) 0,85 (0,52-1,40) 0,78 (0,40-2,00) 0,95 (0,60-1,58) 0,70 (0,39-1,20) 1,56 (0,74-3,20) 0,75 (0,34-1,60) 0,65 (0,25-2,20) 0,25 0, Better for Active Group Better for Control Group

16 Medical Reaction Delay CONTROL Group Restropective analysis* Medical reaction delay or p<0.001 Temporal gain in early detection of events: 117 days 145 ± 120 days HM events Managed Event HM events Managed Event Gained time with HM 28 ± 28 days ACTIVE Group ACTIVE CONTROL * To allow a retrospective analysis, the control group patients were equipped with Blinded Remote Monitoring. Quality of Life SF36 Physical health Mental health Total score SF-36 ACTIVE Group CONTROL Group p=n.s

17 Total Follow-Ups over time 601 FUs in Control group vs 389 FUs in Active group Number of FUs per patient 3, , , , , , , , , , , , , , % Interim FU p< % after last FU p<0.001 =+1.15/year ACTIVE Group ± 95%CI CONTROL Group ± 95%CI Months -36% =+0.50/year Interim Follow-Ups general practionner call (12) CONTROL group 371 Interim FUs Other * (33) Patient call (21) ACTIVE Group 167 Interim FUs Other * (43) Patient call (30) Standard of care (308) - 56% p<0.001 general practionner call (21) Home Monitoring (73) * Other = pre, post, or during hospitalisation No interim FU for 51% patients in the active group

18 73 FUs triggered by Home- Monitoring Home-Monitoring & Web Site Patient file Interim FU 34 Clinical events (47%) 82% leading to clinical intervention Detection Mean: 7.3±6.6 months 39 Technical events (53%) 67% leading to clinical intervention Detection Mean: 4.6±3.7 months Switch mode / AF 39% Ventr rate 7% Transmission Failed 10% Automatic Capture Control 14% Threshold 20% Lead 3% P/R wave 7% Unnecessary follow-ups Interim FUs more contributory in the active group % Not Useful FUs 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% ACTIVE Group CONTROL Group p< % 38% Interim FU p=ns 73% 79% 18 Months

19 Presentation Overview Conclusion REMOTE MONITORING for the patients implanted with Pacemaker: is safealternative to conventional care: the proportion of patients with one or more event was not higher in the active group than the control group provides early detection of events reduces atrial arrhythmia events and related strokes decreases the number of FUs COMPAS COMPArative Follow-up Schedule with Home Monitoring has not impact on quality of life Home Monitoring for Pacemaker Follow-Up: The first prospective randomised trial Polyclinique de Bourgogne C.H.P. Saint Martin COMPAS COMPArative Follow-up Schedule with Home Monitoring C.H.U Chateauroux

20 @ ECOST Effectiveness and Cost Of ICD follow-up Schedule with Telecardiology Principal investigator: Pr Salem KACET Primary Objective: ECOST: Study Design The study investigates whether home monitoring follow-up has an impact on the number of patients with more than one Significant Serious Adverse Event (SSAE) since homemonitoring activation. SSAE : composite events comprising : All-cause mortality Cardiac serious adverse events Device serious adverse events

21 Methodology: ECOST: Study Design The investigation compares two groups : CONTROL Group, i.e. patients receiving the standard of care. Due to safety concerns, the patients are followed every 6 months after a firstfollow-up (between 1 and 3 months after implantation). ACTIVE Group, i.e. patients followed with home-monitoring. After a first follow-up, the patients are followed one time per year. Within this period, the additional ICD follow-up or therapeutic intervention will be primarily triggered on cardio-reports reception, Data/IEGM-online analysis on internet site or patient/physician call. ECOST is a clinical study - prospective - multicenter - randomized ECOST: Study Design Timeline Enrolment Implantation Discharge/Rando 1-3 months Control Group 9 months 15 months 21 months 27 months Active Group Mandatory follow up Additional follow up triggered by Home-Monitoring Additional follow up triggered by Patient and/or Physician

22 Secondary Objectives: ECOST: Study Design A complete evaluation of Home-Monitoring «Costs minimization»analyse Home-monitoring workload Quality of life SF-36 Costs / Effectiveness analyse Contingent evaluation Number of Adverse Events (AE) Delay of Home Monitoring to manage AE Sensitivity of Home Monitoring to detect ICD dysfunctions Inappropriate therapies rate and impact on hospitalization Number of ICD charge and impact on ICD-battery longevity ECOST: Study Design Key Inclusion criterias: Indication for single or dual chamber ICD (without CRT) Key Exclusion criterias: NYHA class IV Pregnant woman or woman who plan to become pregnant during the trial Patient whose medical situation is not stable Presence of any disease, other than patient's cardiac disease, associated with reduced likelihood of survival for the duration of the trial, e.g. cancer, uraemia (urea >70mg/dl or creatinine >3mg/dl), liver failure, etc. Age <18 years Patient unable to handle Home Monitoring system correctly The patient is not willing and able to comply with the protocol Change of residence expected during study Insufficient GSM coverage at patient's home Participation in another clinical study Patient unwilling to sign the consent for participation.

23 Enrolment 473 patients enrolled between January 2007 and April sites in FRANCE Patients were implanted with Lumos or Lumax VR-T/DR-T Any legally marketed leads may be used Two group randomization (1:1 ratio): BIOTRONIK Home Monitoring = ON (ACTIVE Group) BIOTRONIK Home Monitoring = OFF (CONTROL Group) Patient participation and follow up period: Up to 27 months ECOST Clinical Case 1 LUMOS VR-T for Brugada syndrome, Men 57 yo in the contrôle group (no telemonitoring) Implantation ICD 19/04/07 PATIENT CALL For shock 22/05/07 Additional clinic 23/05/07 During additinal clinic 447 charges 4 inappropriate shocks Battery status: MOL2 23% charge shock

24 Cas Clinique 2 Cas Clinique 2 Surdétection de l onde T Le choc a étéannulémais le risque de choc inappropriéesr élevé: tracéde fin d épisode

25 Cas Clinique 2 Le patient est appeléen consultation. Avant même qu il soit présent les réglages sont définis: Solutions: Allonger le blanking post-stim V Allonger le critère de détection de détection des FV de 8/12 à12/16 Cas Clinique 2 1 semaine plus tard nouvel épisode de FV choqué Le choc est approprié

26 Contributions of Remote Monitoring to the Follow-up of Implantable Cardioverter Defibrillator Leads under Advisory Professeur Salem KACET Chef du Service de Cardiologie A Rythmologie et Stimulation cardiaque CHRU de Lille- Hôpital Cardiologique F Lille Lead fractures and advisory Lead fracturescan cause inappropriate shocks, failure to defibrillate or loss of pacing function, some of these events being potentially lethal Last advisory in 0ctober 2007(Medtronic Inc. Sprint Fidelis Defibrillator Leads): recommendation of a tighter follow-up schedule Lead fractures may be preceded by asymptomatic abnormal lead behaviour(impedance, over sensing, under sensing)

27 Reaction of Ecost Safety Committee How to monitor patients with Sprint Fidelis Lead in the Ecost trial? Decision of the security committee: Conventional follow up every 3 months in accordance with manufacturers guidelines Activation of Home-Monitoring in both patients groups Setting of pacing impedance alerts on Home-Monitoring service center in accordance with Medtronic guidelines Patients followed in a register Objectives of this analysis How the remote monitoring (RM) of ICDs may be used to improve the quality of care and can detect lead fractures? Usefulness of recommended 3-month interval leads FU? This analysis describes 2-year observations with RM in recipients of Sprint Fidelis lead

28 Patient Population Number of patients Age Gender (male) 40 63,6 ±11,7 35 LVEF (%) 34,6±13,7 Primary prevention (%) 55 NYHA I (%) 15,7 NYHA II (%) 65,8 NYHA II (%) 18,5 Follow up Mean FU after ICD implantation: 22 ±4 months Mean number of FU visits after the warning issued by AFSSAPS 5.1 ±1.5, over 17 ±3 months (median 18; range 8-18) 3.8 ±0.9 visits per patient per year FU triggered by HM suspicion of lead dysfunction in 4 out of 40 pts: 3 lead fractures confirmed

29 Pacing Impedance of the 40 leads Average of the pacing impedance: 570 ±122 ohms Clinical case 1 : Lead fracture with sensing of noise and no abnormal change in impedance ICD Implant 18/04/07 History since implantation: FU Alert AFSSAPS FU 05/07/07 16/10/07 10/01/08 19/06/08 29/11/08 FU FU VF episode 09/12/08 Lead replacement 17/12/08 Patient management: 09/12/08: Non sustained VF episode. Online EGM: oversensing of noise 11/12/08: Additional FU: Lead fracture confirmed 17/12/08: Lead and ICD replacement Lead fracture detected by Home Monitoring (nsvf episode) No inappropriate therapy was delivered Lead fracture detected 10 days after a conventional FU Patient management 2 days after the Home-Monitoring Event

30 Clinical case 1 : Lead fracture with sensing of noise and no abnormal change in impedance nsvf detected by Home-Monitoring: Pacing impedance (ohm) Clinical case 2 : Lead fracture with sensing of noise and impedance rise History since implantation: ICD Implant 10/04/07 FU Alert AFSSAPS FU FU FU 06/07/07 16/10/07 13/03/08 23/06/08 18/09/08 HM Event Lead replacement 22/12/08 15/12/08 Patient management: 15/12/08: First HM event: Increasing impedance from 540 to 773 ohms 16/12/08: Second HM event: ns VF episode. Online EGM: oversensing of noise. Immediate hospitalization 22/12/08: Lead replacement Lead fracture detected by HM (increasing impedance and ns VF episode) No inappropriate therapy was delivered Immediate Patient management

31 Increasing pacing impedance: Clinical case 2 : Lead fracture with sensing of noise and impedance rise nsvf detected by Home-Monitoring: Clinical case 3 : Lead fracture with sensing of noise, impedance rise and shocks delivery ICD Implant 29/03/07 History since implantation: FU Alert AFSSAPS FU FU/ HM (T wave oversensing) 13/06/07 16/10/07 20/12/07 13/03/08 25/04/08 30/06/08 FU FU / HM (Imp V>1000) 3 inappropriate shocks. Lead replacement 05/07/08 Patient management: 30/06/08: Increasing impedance from 600 to 1294 ohms detected by Home-Monitoring. Yet, no anomaly detected during additional FU with a 734 ohms impedance. 05/07/08: 3 inappropriate shocks delivered. Hospitalization for lead replacement Lead anomaly detected by HM (increasing impedance) 3 inappropriate shocks delivered Immediate Patient management

32 Clinical case 3 : Lead fracture with sensing of noise, impedance rise and shocks delivery Increasing pacing impedance from 600 to 1294 ohms: VF detected by Home-Monitoring: Clinical case 4: No lead fracture and rise of impedance >2,000 Ω History since implantation: ICD Implant Alert AFSSAPS FU Follow up triggered by HM: ImpV>2000 FU Follow-up 10/10/07 16/10/07 05/12/07 10/01/08 13/03/08 Patient management: -Regular increasing impedance until HM-Event Pacing impedance (ohms) -10/01/2008: Additional FU: threshold and pacing impedance measured twice daily (0,6V/0,5ms; 1344 and 1521 ohms). No anomaly detected - Decision: no intervention and control by HM -Stabilization 10/01/08

33 Rate of ICD controls The rate of ICD controls complies with the guidelines of competent authorities and is 1.74 times more than Ecost control group 4 Mean number of FU per patient/year 3,5 3 2,5 +74% (p<0.001) 2 1,5 3,79 ±0,93 2,18 ±0,98 1 0,5 0 Fidelis Register 1 Sample of ECOST 2 Control Group (n= 40) (n= 100) Trigger mode and usefulness of FU 10,2% 87,6% 4,9% 7,5% 27 % 89,8% 73 % Conventional Follow up Follow up triggered by Home-Monitoring Unscheduled follow up Non Actionable Actionable

34 Conclusion The failure rate of the Sprint Fidelis Lead was 7.5%after a mean FU of 22 ±4 months Home Monitoring allowed early and reliable detection of all 3 lead fracturesthanks to impedance rises and noise detection 90% of scheduled follow-ups were not actionable

35 COMPAS