Transcript 心房颤动抗栓治疗路在何方? --反方：未来在左心耳封堵术

心房颤动抗栓治疗路在何方?
--反方：未来在左心耳封堵术
薛玉梅
广东省心血管病研究所
广东省人民医院
>5X
非瓣膜房颤血栓主要来源左心耳
trial
3.1 Non-
ting
ong-
ation 1-27-09
3.2
Thromboelmbolic
stroke
13%
Non-LAA
87%
10%
90%
Thromboelmbolic
stroke
Thrombus
Originate LAA
AHA Statistical Update: Heart Disease and Stroke Statistics-2008 Update;
NHLBI and ARIC Circulation 1-29-08
Hylek EM, et.al. NEJM. 2003; 349: 1019-1026
Johnson. Eur J Cardiothoracic Surg 2000;17
LAA
Devices
LAA
封堵器
LAA Devices
BSc/WATCHMAN®
BSc/WATCHMAN®
SJM/ACP ®
BSc/WATCHMAN
Sentreheart/Lariat ®
SJM/ACP ® Sent
Lifetech/MDT/Lambre ®
Clinic
trials
about
WM
Clinical
Studies
STUDY
PATIENTS
SITES
66
8
(4 US, 4 EU)
PROTECT AF
WATCHMAN
COMMENTS
•
•
•
318 patient years of follow-up
30 patients with 5+ years of follow-up
Enrollment complete, continue to follow patients on annual
basis
800
59
(55 US, 4 EU)
•
•
•
1,500 patient years of follow-up
27 months average follow-up per patient
Enrollment complete, continue to follow patients for 5 years
Continued Access Registry
(CAP)
566
26
(24 US, 2 EU)
•
•
Significantly improved safety results
Enrollment complete, continue to follow patients for 5 years
ASAP
150
4
(4 EU)
•
•
Treat patients contra-indicated for warfarin
Enrollment complete, continue to follow patients for 2 years
EVOLVE
69
3
(3 EU)
•
•
Evaluate next generation WATCHMAN
Enrollment complete, continue to follow patients for 1 year
•
•
•
•
Same endpoints as PROTECT AF
Revised inclusion/exclusion criteria
Initial enrollment November 2010
Enrollment up to 400 randomized, anticipated enrollment
completion June 2012
Pilot
PREVAIL
369
Total
2,020
≤50
PROTECT AF
Protect – AF Trial
Study Objective:
Evaluate the efficacy and safety of the WATCHMAN LAA Closure
Device as compared to long-term warfarin therapy in patients with
non-valvular atrial fibrillation and CHADS2 score > 1
Study Design:
Prospective, randomized (2 Device: 1 Control), non-inferiority
study of the Watchman device compared to long-term warfarin
therapy
Primary Endpoint:
Non-inferiority of the WATCHMAN device to warfarin therapy for
the composite of ischemic stroke, hemorrhagic stroke, systemic
embolism and cardiovascular/unexplained death
Additional Endpoints:
Life-threatening events including device embolization requiring
retrieval, pericardial effusion requiring intervention, cranial and
GI bleeding, and bleeding requiring transfusion > 2 units PRBCs
Patient Population:
WATCHMAN n=463
Control
n=244
Roll-in
n=93
Number of Sites:
59 (55 U.S., 4 EU)
Therapy Timeline
Therapy Timeline
PostImplant
Day 0
Day 45
Day 180
Ongoing
Day 2-14
WATCHMAN
Pre-implant interval
Patient gets WATCHMAN
Patient takes Warfarin
Patient discontinues Warfarin / takes Clopidogrel
Patient discontinues Clopidogrel
Control
Randomize
Control patient takes Warfarin
Day 0
Ongoing
PROTECT AF –
Primary
Efficacy
– Efficacy
1065 pt yrs
PROTECT
AFEndpoint
– Primary
Endpoint
38% Reduction
10.0%
9.0%
8.0%
38% lower
29% lower
7.0%
Incidence Rate (%)
6.0%
PNI = >99.9%
PNI = 99.3%
PNI = >99.9%
PNI = >99.9%
4.9%
5.0%
4.0%
3.0%
3.2%
3.0%
2.7%
2.3%
2.0%
1.0%
0.7%
0.3%
0.0%
Primary Efficacy
WATCHMAN Group
N=463
SH-83112-AA MAY2012
All stroke
Cardiovascular/
Unexplained Death
Warfarin Group
N=244
0.0%
Systemic Embolism
PNI = Posterior non inferiority Probabilities
David R Holmes, Lancet Vol 374 August 15, 2009
David R Holmes, Lancet Vol 374 August 15, 2009
Primary Efficacy Endpoint
Primary Efficacy Endpoint
PROTECT
AF
– Primary
Efficacy
(Stroke, Cardiovascular
Death, Systemic
Embolism) Endpoint
0.20
Control
Device
Probability
0.15
0.10
0.05
0.00
H-83112-AA MAY2012
0
365
730
1095
Days Since Randomization
244
463
174
332
67
132
17
34
Control
Device
David R Holmes, Lancet
VolR374
August
15,Vol
2009
David
Holmes,
Lancet
374 August 15, 2
PROTECT AF –
Primary
Safety Endpoint
PROTECT
AF – Primary Safety Endpoint
Primary Safety Endpoint
0.20
Control
Device
Probability
0.15
Peri-procedural events
0.10
On going
bleeding events
0.05
0.00
0
365
730
1095
Days Since Randomization
244
463
SH-83112-AA MAY2012
171
317
65
126
16
30
Control
Device
David R Holmes, David
Lancet
Vol 374 August 15, 2009
R Holmes, Lancet Vol 374 August 15, 2009
PROTECT AF
– All Stroke
PROTECT
AF – All Stroke
All Stroke
0.15
Control
Device
Ongoing stroke risk
in the Warfarin group
Probability
0.10
Peri-procedural stroke
0.05
0.00
SH-83112-AA MAY2012
0
365
730
1095
Days Since Randomization
244
463
174
332
67
132
17
34
Control
Device
David R Holmes, David
Lancet
Vol 374 August 15, 2009
R Holmes, Lancet Vol 374 August 15, 2009
PROTECT
CauseMortality
Mortality
PROTECT
AF –AF
All– All
Cause
All Cause Mortality
0.20
Control
Device
Probability
0.15
0.10
0.05
0.00
0
365
730
1095
Days Since Randomization
244
463
176
337
68
136
17
35
Control
Device
David R Holmes, Lancet Vol 374 August 15, 2009
Recently reported results from studies on percutaneous LAA occlusion
Lewalter T, et al. Europace, 2013, 15: 652-656
Watchman
Amplatzer
cardiac plug
Reddy V, et al. Circulation 2011;123:417–24
Reddy V, et al. Paper presented at: HRS, 2012
Walsh K. Paper presented at: EuroPCR, 2012
Kefer J, et al. Paper presented at: EuroPCR, 2012
Meerkin D, et al. Paper presented at: EuroPCR, 2012
Stroke rates from recently reported studies on
percutaneous LAA occlusion
Lewalter T, et al. Europace, 2013, 15: 652-656
Reddy V, et al. Paper presented at: HRS, 2012
Walsh K. Paper presented at: EuroPCR, 2012
Kefer J, et al. Paper presented at: EuroPCR, 2012
Meerkin D, et al. Paper presented at: EuroPCR, 2012
LAA Closure vs. NOAC
PROTECT AF vs. RE – LY
PROTECT AF vs. RE – LY
PROTECT AF
RE – LY
Medical Device (WATCHMAN) to
Drug (Warfarin) comparison
Drug (Dabigatran) to Drug
(Warfarin) comparison
Study design and Number of
patients studied
Prospective RCT, 800 patients
Prospective RCT, 18,000
patients
Efficiency endpoint definition
All stroke, systemic embolization
and CV death
All stroke, systemic
embolization
2.2
2.1
66%
64%
Study Purpose
CHADS2 Score
Time in therapeutic range for
Warfarin patients
Results
Relative risk
Relative risk WATCHMAN vs.
warfarin – 0.71
Dabigatran (110 mg) vs.
warfarin – 0.91
Relative risk Dabigatran
(150 mg) vs. warfarin – 0.66
David R Holmes, Lancet Vol 374 August 15, 2009
Stuart Connolly, NEJM 2009;361
PROTECT AF vs. RE – LY
AF vs. RE
vs. Device Consideration
DrugPROTECT
– LY
Drug vs. Device Consideration
Device
Drug
Systematic Solution
Local Solution
Long Term Risk
Short Term Risk
(continual bleeding events)
(complications during implant)
20% discontinue drug
After successful implant & follow-up, 87%
can discontinue Warfarin
Dabigatran- Twice daily dose compliance is
needed, has a half life period of 17 hours
requiring 2 daily doses to maintain benefit
No on-going activity needed to maintain
benefit of WATCHMAN
Dabigatran effect not reversible if bleeding
develops
Risk is of bleeding due to device
is primarily in the procedure or periprocedure
David R Holmes, Lancet Vol 374 August 15, 2009
Stuart Connolly, NEJM 2009;361
Protocol required a minimum of 20% of subjects enrolled at new centers and
25% of subjects enrolled by new operators
18 out of 41 centers did not have prior WATCHMAN experience
40% of patients enrolled at new sites by new operators
“learning curve”-PREVAIL
• Protocol required
a minimum
Implants of 20% of
% of Successful
subjects enrolled at new centers and 25%
98.0%
96.0%
92.0%
90.0%
of subjects enrolled
by new94.0%
operators
Success
Implantof
• Study
18 out
41 centers did not have prior
WATCHMAN experience
Experienced Operators
N= 26
• 40%
of patients enrolled at new sites by
newNew
operators
Operators
95%
96.2%
93.2%
N= 24
p = 0.282
Lewalter T, et al. Europace, 2013, 15: 652-656
Summary
• LAA Closure can effectively prevent AF patients
from stroke
• After successful implant, 87% patients can
discontinued OAC
• The continual bleeding risk of NOAC should be
take into consideration
LAA closure is BETTER than
anticoagulation therapy for AF !