PowerPoint Presentation
Which Wins? Warfarin or Watchman?Innovations in atrial
fibrillationDr Jason SharpConsultant & Interventional
CardiologistSydney Adventist HospitalHornsby Ku-ring-gai
Hospital
SH-102103-AD- APR 2013Thrombus in LAA
SH-102103-AD- APR 2013Patient Name good comment, patient name
should be taken out, without video access we cant do it
91% of stroke in AF is caused by blood clots that form in the
left atrial appendage (LAA)11 Blackshear JL. Odell JA., Annals of
Thoracic Surgery. 1996;61:755-759Fibrillation causes blood to
stagnate in the LAAThe stagnant blood becomes an ideal environment
for a thrombus or blood clot to formThe blood clot, or portion of
it, dislodges from the LAA and travels through arterial systemThe
embolism lodges itself in the blood vessels of the brain,
restricting blood flow and causing a strokeImages on file at Boston
Scientific CorporationThrombus in the LAA
SH-102103-AD- APR 2013
3
European Society of Cardiology Guidelines2CHA2DS2VASc is a newer
scoring systemCHA2DS2VASc, developed by Lip et al, is a refinement
of the older CHADS2 Score which includes additional stroke risk
factors and puts greater emphasis on age as a risk factor11 Lip GY
et al, Chest. 2010;137(2):263-722 Camm AJ et al, Eur Heart J.
2010;31:23692429Condition/Risk FactorPointsCCongestive heart
failure1HHypertension1AAge 75 years2DDiabetes mellitus1S2Previous
stroke or TIA2VVascular disease1AAge 65-74 years1ScSex (female
gender)1
CHA2DS2-VASc ScoreTreatment0No treatment1Aspirin or warfarin or
dabigatran2Warfarin or dabigatran
SH-102103-AD- APR 2013
4
HAS-BLED, developed by Pisters et al, allows clinicians to
assess an individuals risk of bleeding based on comorbidities1In
determining when oral anticoagulation is appropriate, clinicians
must balance the CHADS2 or CHA2DS2VASc score against
HAS-BLEDUnfortunately, a high CHADS score often correlates with a
high HAS-BLED score and these patients do not receive
anticoagulation due to the high bleeding riskHAS-BLED risk of
bleedingHASBLEDRisk of major bleeding in patients with AF in the
Euro Heart Survey1 Pisters R et al. Chest
2010;138(5):1093-100Hypertension, stroke and age are also variables
in the CHADS scores
ConditionPointsHHypertension1AAbnormal liver and renal function
(1 point each)1 or 2SStroke1BBleeding1LLabile INR1EElderly (age
>65)1DDrugs or alcohol (1 point each)1 or 2
ScoreBleeds Per 100 Patient Years01.1311.0221.8833.7448.7
SH-102103-AD- APR 2013WATCHMAN LAA Closure TechnologyThe
WATCHMAN device reduces the risk of stroke by closing off the left
atrial appendage, which is known to be the main source of blood
clots in patients with atrial fibrillation
Johnson, Eur J Cardiothoracic Surg 2000:17
SH-102103-AD- APR 2013
WATCHMAN Device
Nitinol FrameRadially expands to maintain position in
LAAAvailable sizes:21, 24, 27, 30, 33 mm (diameter)10 Active
fixation anchors around device perimeter designed to engage LAA
tissue for stability and retentionContour shape accommodates most
LAA anatomies160 Micron MembranePolyethylene terephthalate (PET)
capDesigned to block emboli from exiting the LAAIntended to promote
healing process
Anchors160 Micron Membrane
SH-102103-AD- APR 2013
45-day follow-up: healing process
Canine Model 30 dayCanine Model 45 dayHuman Pathology - 9
monthspost-implant (non-device related)Schwartz J Am Coll Cardiol
Inv 2010:3
SH-102103-AD- APR 2013
PROTECT AF1,6CAP2ASAP3,4PREVAIL5Trial DesignProspective RCT with
patients able to take warfarinProspective registry with patients
able to take warfarinProspective registry with patients
contraindicated for warfarinProspective RCT with patients able to
take warfarinOutcomeWATCHMAN was non-inferior to warfarin in
patients at high-risk of thromboembolismSignificantly improved
safety results from early PROTECT AF experienceIschemic stroke rate
significantly reduced in warfarin contra-indicated patientsWATCHMAN
device was safely implanted by new operatorsMean age
/CHADS272/2.274/2.472.4/2.874/2.6Total Enrolled Subjects707
randomized1 93 pts rolled in2460150407Total Patients
Implanted5422437142269Implantation
Success89.5%295.0%94.7%95.1%Primary Efficacy (all-stroke,
CV/unexplained death, and systemic embolism)40% reduction vs.
warfarin629% reduction vs. warfarinN/A0.064Identical 18-month rates
for WATCHMAN and warfarinAll-Stroke32% reduction vs. warfarin623%
reduction vs. warfarin77% reduction vs. expected rate per CHADS
scoreData not yet availableSafety(7 day
procedure-related*)8.7%54.1%553% reduction vs. PROTECT
AFPericardial effusion with tamponade=1.3%Major
bleeding=2.7%4.4%49% reduction vs. PROTECT AF
*Composite of vascular complications includes cardiac
perforation, pericardial effusion with tamponade, ischemic stroke,
device embolization, and Includes observed PE not necessitating
intervention, AV fistula, major bleeding requiring transfusion,
pseudoaneurysm, hematoma and groin bleeding1 Holmes DR et al.
Lancet 2009;374:53442; 2 Reddy VY et al. Circulation. 2013;
127:720-729; 3 Sievert H. TCT 2011; 4 Reddy, JACC 2013; 5 Homes DR
PREVAIL Mar 2016 Reddy, et al. HRS LBCT 2013
WATCHMAN Clinical Program
At 4yrs WATCHMAN was superior to warfarin in primary efficacy,
all-cause mortality, & cardiovascular deathSH-AA-159901-MAY
2013
SH-102103-AD- APR 2013WATCHMAN PROTECT AFHolmes, et al., Lancet
2009; 374: 53442Study ObjectiveEffectiveness and safety of LAA
closure for prevention of stroke in comparison to Coumadin for
non-valvular A-fib patientsStudy DesignProspective, randomized
(2:1), non-inferiority trial of LAA closure vs. warfarin in A-fib
patients for prevention of strokePrimary EndpointEfficacy:
Composite end point of stroke, cardiovascular death or systemic
embolizationSafety: Major bleeding, device embolization or
pericardial effusionPatient Populationn = 707Mean CHADS2=2.2Mean
Follow-Up1065 Patient-years, 18 months (Holmes, et al., Lancet
2009; 374: 53442)1588 Patient-years, 2.31.1 years (Reddy, et al.,
Circ 2013)2,621 patient-years, 4 years (Reddy, et al., HRS LBCT
2013)Number of Sites59 in the United States and Europe
SH-AA-159901-MAY 2013
SH-102103-AD- APR 2013WATCHMAN PROTECT AF
WATCHMAN therapy is non-inferior to warfarin in the prevention
of stroke and death.38% reduction with WATCHMAN for the composite
endpoint for efficacy (including strokes, CV or unexplained death,
and systemic embolism) when compared to warfarin Following the
periprocedural period, the rate of ischemic stroke with the
WATCHMAN Device was 1.3 per 100 patient years vs. 1.6 with warfarin
Holmes, et al., Lancet 2009; 374: 53442Events in PROTECT AF trial
at 1065 patient years (18m)PNI >99.9%PNI >99.9%PNI >
99%38% lower29% lower38% lower
WATCHMAN GroupN=463Warfarin GroupN=244PNI = Posterior non
inferiority ProbabilitiesRate per 100 patient years
Indications, contraindications, warnings and instructions for
use can be found in the product labeling supplied with each device.
Information for the use only in countries with applicable health
authority product registrations
SH-102103-AD- APR 2013WATCHMAN PROTECT AF 4 Yrs.Reddy, et al.,
HRS LBCT 2013
Local therapy with WATCHMAN was superior to Warfarin 40%
reduction of stroke / systemic embolism / CV death60% reduction in
Cardiovascular Mortality34% reduction in All-Cause MortalityEvents
in PROTECT AF trial at 2,621 patient years (4y)Rate per 100 patient
yearsWATCHMAN GroupN=463
Warfarin GroupN=244
PS >99%PS > 82.5%40% lower32% lower60% lower
Ps = Posterior Probability for SuperioritySH-AA-159901-MAY 2013
Indications, contraindications, warnings and instructions for use
can be found in the product labeling supplied with each device.
Information for the use only in countries with applicable health
authority product registrations34% lower
P=0.0379P=0.0045
SH-102103-AD- APR 2013WATCHMAN Net Clinical BenefitStudy
ObjectiveEvaluate the net clinical benefit of using the WATCHMAN
device by combining annualized rates of ischemic stroke,
intracranial haemorrhage, major extracranial bleeding, pericardial
effusion, and death, weighted to reflect the impact of these events
relative to death and disabilityStudy DesignPost-hoc analysis of
outcomes in 707 patients in the PROTECT AF trial and 566 patients
in the CAP registry undergoing LAA closure with the WATCHMAN device
compared to standard anticoagulation Follow-Up2,364 total patient
years
Gangireddy, S.R., et al., European Heart Journal 2012; DOI:
10.1093/eurheartj/ehs292SH-AA-159901-MAY 2013
SH-102103-AD- APR 2013WATCHMAN Net Clinical Benefit
In PROTECT AF the NCB shifted from warfarin to WATCHMAN between
6-9 months post implant.Due to PEs and procedure-related stroke
events.NCB favored WATCHMAN as early as 3 mos post implant in CAP
registry.
Gangireddy, S.R., et al., European Heart Journal 2012; DOI:
10.1093/eurheartj/ehs292SH-AA-159901-MAY 2013
SH-102103-AD- APR 2013WATCHMAN PROTECT-AF Analysis of Older
Patients >75 yrs.95% of stroke were ischemic, non-inferiority
P-valuesITT Patient Population
Fewer events were shown in the WATCHMAN group in the primary
efficacy endpoints, all stroke, and all-cause mortality. P75
yrs.ITT Patient Population
Older patients have a higher risk of bleeding, making it
important to manage this risk (Mean CHADS2 score of 2.8 vs. 2.2 in
the full study population).WATCHMAN had a lower major bleeding rate
than warfarin once procedure-related events were
excluded.EVENTDevice (n=190)Rate (events/patient-years)Control
(n=115)Rate (events/patient-years)Major bleeding6.1 (23/374.8)5.1
(13/252.8)Procedure related major bleeding2.9 (11/385.9)Or 11
events/190 pts (5.8% pts)NANon-procedure related major bleeding3.3
(13/393.3)5.1 (13/252.8)
Kar, S. TCT 2012; PROTECT-AF: Watchman LAA Closure in AF
Patients 75 YearsSH-AA-159901-MAY 2013
SH-102103-AD- APR 2013Mr AC78yo retired publican. Hypertension.
Mild coronary disease. NIDDM diet controlled.CVA 2008 documented on
MRI. Minimal residual problems. Found to be in AF at the time.
Failed cardioversion. Started on warfarin.Presents with bright
rectal bleeding. INR 2.2. Significant blood loss requiring 3 units
packed cells.Colonoscopy: severe diverticular disease likely
diverticular bleedPLAN?
SH-102103-AD- APR 2013But not everyone with a high CHADS VASC
score is suitable for oral anticoagulation
Even with the NOACs
SH-102103-AD- APR 2013WATCHMAN Preliminary Results ASA Plavix
Feasibility StudyStudy ObjectiveTo evaluate the safety and
feasibility of the WATCHMAN Left Atrial Appendage Closure device
for the treatment of non-valvular atrial fibrillation in patients
with a contraindication to warfarinStudy DesignMulticenter,
nonrandomized, feasibility study Primary EndpointThe primary
efficacy endpoint was defined as the combined events of ischemic
stroke, hemorrhagic stroke, systemic embolism, and
cardiovascular/unexplained death.Patient Populationn = 150Mean age
72.5 4 yrs.Mean CHADS2=2.8Mean CHA2DS2-VASc=4.4Mean Follow-Up14.4
monthsNumber of Sites4 centers (Prague, Leipzig, Regensburg, and
Frankfurt)
Reddy, et al. JACC. 2013; In Press.SH-AA-159901-MAY 2013
SH-102103-AD- APR 2013WATCHMAN Preliminary Results ASA Plavix
Feasibility Study
WATCHMAN Implantation for contra-indicated AF warfarin patients
is: Feasible Low, but manageable, rate of device thrombus Decreases
the rate of stroke by 77%
5.0%64%Reddy, et al. JACC. 2013; In Press.SH-AA-159901-MAY
2013
SH-102103-AD- APR 2013
Discussion on patient profiles
1 - Non-valvular AF: excluding rheumatic valvular diseaseor
prosthetic heart valves
2 - For contraindications, refer to Instructions for use ofthe
anticoagulants drugs
NOACs (dabigatran, rivaroxaban, and apixaban) arenot recommended
in patients with severe renal impairme(CrCl
