Safety and efficacy results in the EWOLUTION all-comers LAA closure study: DAPT subgroup

Transcription

1 Safety and efficacy results in the EWOLUTION all-comers LAA closure study: DAPT subgroup Martin W. Bergmann, Hüseyin Ince, Stephan Kische, Thomas Schmitz, Felix Meincke, Boris Schmidt, David Foley, Timothy R. Betts, Marek Grygier, Alexey V. Protopopov, Kenneth M. Stein, Lucas V.A. Boersma on behalf of the EWOLUTION investigators

2 Potential conflicts of interest Speaker's name: Martin W. Bergmann I have the following potential conflicts of interest to report: Receipt of grants / research supports: Boston Scientific Receipt of honoraria or consultation fees: Bayer AG, Boston Scientific, DAIICHI SANKYO and ELI-LILLY, St. Jude Medical

3 Background ESC Guidelines atrial fibrillation 2016: platelet inhibition is ineffective in stroke prevention ESC Guidelines atrial fibrillation 2016: IIB recommendation for LAA closure as stroke prevention in AFib patients when long-term oral anticoagulation is contraindicated Randomized trials on WATCHMAN (PROTECT-AF, PREVAIL) vs. OAC showing non-inferiority included warfarin-eligible patients Safety and efficacy of LAA closure in warfarin-ineligible patients less well studied Prospective, multi-center, all-comers EWOLUTION registry captures current practice in Europe with WATCHMAN implantation 1-year safety and efficacy in the EWOLUTION DAPT subgroup allows to judge on stroke prevention following LAA closure in the absence of oral anticoagulation

4 Informed consent obtained: N = 1025 EWOLUTION: patient flow to 1 year Boersma et al. presented at HRS 2017 Anatomy considered not suitable at prescreening: N = 5 EuroPCR presentation DAPT treatment after LAA closure Implant of WATCHMAN: N = 1020 Study population Implant of WATCHMAN: N = 605 DAPT subgroup Patients with successful Watchman implant: N = 1005 Patients with successful Watchman implant: N = 605 End of study < 1 year (N = 112) Deceased: N = 91 Withdrawn: N = 8 Lost-to-FU: N = 13 End of study < 1 year (N = 75) Deceased: N = 58 Withdrawn: N = 6 Lost-to-FU: N = 11 Active 1 year: N = 893/1005 (89%) Pts with TEE: N = 875/1005 (87%) Pts with > 11m of data: 804/893 (91%) Active 1 year: N = 530/605 (88%) Pts with TEE: N = 525/605 (87%) Pts with > 11m of data: 473/530 (90%)

5 Patient characteristics in EWOLUTION DAPT subgroup DAPT n=605 Number of subjects months follow-up available 90% Age 80yrs old 31.1% OAC contraindicated 83.8% CHA 2 DS 2 -VASc score (mean+/- SEM) 4.6± 1.6 CHA 2 DS 2 -VASc score 3 n=540 (89%) HAS-BLED score (mean +/- SEM) 2.4 ± 1.2

6 EWOLUTION DAPT subgroup device thrombus 4.0% TEE follow-up N=525 pts (87%) 96% Clean Thrombus DAPT n=605 Follow-up TEE 525/605 (87%) Effective first TEE follow-up > 4 weeks 99.2% Thrombus on the device at follow-up TEE** 4.0%, n=22 stroke/tia in patients with thrombus 1

7 Medication switch after WATCHMAN LAA occluder therapy followed by DAPT therapy Time to DAPT Discontinuation DAPT discontinuation % 17% m 3-6m 6m - 1 yr > 1 yr 5% switch to single APT stay in DAPT switch to no meds transient switch to (N)OAC 7%

8 % pts on DAPT Duration of DAPT therapy: 3, 6 or 12 months days

9 survival % pts on probability DAPT Safety: major bleeding 1 year DAPT n=605 Major Bleeding SAEs 2.5% (19/770 PY ) Major Bleeding SAEs excluding procedural < 7days 2.1% (16/772 PY) Fatal bleeding 0.5% (4/782 PY) days

10 Safety of LAA-occluder therapy: SAE at one year SAE type pulmonary/ COPD DAPT n=605 n=28 pts without SAEs heart failure n=23 major bleeding n=21 AF morbidity n=15 infection n=11 69% 15% 9% unrelated - resolved unrelated - with sequelae related - resolved renal function n=11 coronary artery disease n=10 1.1% 5% 0.3% related - with sequelae death for unknown cause

11 6% 5% Safety: major bleeding 1 year compared to HAS-BLED Expected, based on HAS-BLED* Observed in EWOLUTION 5.1% 5.1% 4% 3% RR 52% RR 60% 2% 1% 2.5% 2.1% 0% Major Bleeding Major Bleeding Excl. Procedural *Effectiveness in bleeding reduction vs. estimated under VKA therapy for comparable HAS-BLED scores based on Lip et al. JACC 2011

12 survival probability Efficacy: ischemic 1 year DAPT n=605 Ischemic Stroke SAEs 1.4% (11/775 PY) Ischemic Stroke/TIA/Systemic Embolism 1.8% (14/771 PY) Haemorrhagic stroke n=0 Fatal stroke n = 0 Disabling stroke n=1 days

13 12% 10% 8% 6% 4% Efficacy: thromboembolic 1 year compared to CHA 2 DS 2 -VASc w/o OAC Expected, based on CHA2DS2-VASc* Observed in EWOLUTION 7.5% RR 81% 10.5% RR 83% 2% 0% Ischemic Stroke 1.4% 1.8% Ischemic Stroke/TIA/SE all events occurred in patients with CHA 2 DS 2 -VASc 3 *Effectiveness in stroke reduction vs. estimated in the absence of therapy for comparable CHA 2 DS 2 -VASc scores based on Friberg et al. EHJ 2012

14 Efficacy: comparison to apixaban in patients with CHA 2 DS 2 -VASc 3 Observed in EWOLUTION DAPT group (N=540) 2.5% Observed in ARISTOTLE* Apixaban subgroup Observed in ARISTOTLE* Warfarin subgroup 2.0% 1.5% 1.61% 1.48% 2.03% 1.0% 0.5% 0.0% Stroke per 100 pt-years

15 Conclusion One year outcome data following LAA closure with the WATCHMAN device find a safety profile as low as other left atrial procedures Bleeding with DAPT most relevant SAE alternatives to DAPT in OAC ineligible patients during the first three months? Efficacy regarding stroke prevention in this high-risk, mostly OAC-ineligible patient cohort similar to randomized trials with OAC eligible patients Stroke rate in EWOLUTION DAPT subgroup similar to ARISTOTLE subgroup CHA 2 DS 2 -VASc ESC Guidelines on atrial fibrillation recommending LAA closure for patients contraindicated for adequate (N)OAC therapy supported by EWOLUTION one-year results

16 Backup Safety: Major bleeding compared to apixaban 5.0% 4.5% 4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% 0.00% Observed in EWOLUTION DAPT group Observed in ARISTOTLE* Apixaban group Observed in ARISTOTLE* Warfarin group 1.36% 2.16% 2.76% 2.25% 3.23% 3.75% 3.46% 4.70% HAS-BLED = 0-1 HAS-BLED = 2 HAS-BLED 3 *Lopes et al. Lancet 2016

17 Backup: Duration of DAPT therapy comparison of 3 vs. 6 months No significant difference found in safety/efficacy endpoints between the short/long DAPT strategy Thromboembolic events: P=0.94 Major Bleeding: P = 0.06 CV or unexplained death: P = 0.17

18 Backup: Mortality in DAPT subgroup of EWOLUTION Mortality cardiovascular 2.6% Alive 90.4% non cardiovascular 5.8% unknown 1.2%