Minimizing Hemorrhagic Minimizing Hemorrhagic complications in ACS and PCI complications in ACS and PCI Insights from OASIS Insights from OASIS-5 and ACUITY 5 and ACUITY Martial HAMON, MD University Hospital of Caen Normandy, France OASIS 5 OASIS 5 Access Access
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Minimizing Hemorrhagic complications in ACS and PCI€¦ · Minimizing Hemorrhagic complications in ACS and PCI Insights from OASISInsights from OASIS--5 and ACUITY5 and ACUITY Martial
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Minimizing Hemorrhagic Minimizing Hemorrhagic complications in ACS and PCIcomplications in ACS and PCIpp
Insights from OASISInsights from OASIS--5 and ACUITY5 and ACUITY
Martial HAMON, MDUniversity Hospital of Caen
Normandy, France
OASIS 5OASIS 5AccessAccess
Prognostic Impact of Major Bleedingin Patients With Acute Coronary Syndromes
Pooled Relative Risks of Mortality Increase*Pooled Relative Risks of Mortality Increase*
in Patients With Acute Coronary Syndromes
Study Major Bleeding No Major Bleeding RR (95% CI)
Deaths, No. / Patients, No.
Random Effects Model
Ali et al 2004 9/89 24/931 3.92 [1.88, 8.18] Eikelboom et al 2006 60/470 833/33676 5.16 [4.04, 6.60] Feit et al 2007 10/194 9/5807 33.26 [13.67, 80.92] Kinnaird et al 2003 44/588 54/8992 12.46 [8.44, 18.39] Lenderink et al 2004 18/98 120/7702 11.79 [7.49, 18.55] Manoukian et al 2007 47/644 159/13175 6.05 [4.41, 8.29] Moscucci et al 2003 85/546 624/15348 3.83 [3.10, 4.72]
Total (95% CI) 450/3644 3003/129953 7.60 [5.55, 10.40]
Rao et al 2005 79/307 549/19110 8.96 [7.28, 11.02] Segev et al 2005 15/79 86/5763 12.72 [7.71, 21.01] Yusuf et al 2006 83/629 545/19449 4.71 [3.79, 5.85]
Test for heterogeneity: Chi² = 85.44, df = 9 (P < 0.00001), I² = 89.5%
T t f ll ff t Z 12 65 (P < 0 00001)
ff f S
Test for overall effect: Z = 12.65 (P < 0.00001)
0.01 0.1 1 10 100
Lower Mortality Higher Mortality
RR (95% CI)
N=133,597 patientsMajor Bleeding 2.7%
Hamon M. et al. EuroIntervention 2007A Systematic Review and Meta-analysis
Random-effects Meta-analysis of 10 Studies(*in hospital or 30-Day)
Primary Endpoint OASIS 5Primary Endpoint OASIS 5Death/MI/RI day 9Death/MI/RI day 9Death/MI/RI day 9Death/MI/RI day 9
ard 0.05
0.06
tive
Haz
a
0.03
0.04
Cum
ulat
0.01
0.02 NS
FondaparinuxEnoxaparin
0 1 2 3 4 5 6 7 8 90.0
Days from randomizationDays from randomization
N Engl J Med 2006;354:1464-76
Major bleeding atMajor bleeding at day 9day 9Major bleeding at Major bleeding at day 9day 9
0 04 E i
0.03
0.04 EnoxaparinHR 0.53
IC 95% 0.45-0.62p << 0.00001ar
d
0.02
p
tive
Haz
a
0.01 Fondaparinux
Cum
ulat
0 1 2 3 4 5 6 7 8 9
0.0
0 1 2 3 4 5 6 7 8 9Days from randomization
N Engl J Med 2006;354:1464-76
Mortality atMortality at Day 30Day 30
Death through day 30
Mortality at Mortality at Day 30Day 30
g y
N Engl J Med 2006;354:1464-76
OASIS 5: Access site substudyOASIS 5: Access site substudy
The aim of this post hoc analysis was to examine The aim of this post hoc analysis was to examine thethe impact of the transimpact of the trans--radial approachradial approach (TRA) in(TRA) inthe the impact of the transimpact of the trans radial approachradial approach (TRA), in (TRA), in comparison to the transcomparison to the trans--femoral approach (TFA) on femoral approach (TFA) on PCIPCI--related:related:
-- major bleedingmajor bleeding-- major bleedingmajor bleeding-- and and patients’outcomespatients’outcomesin a contemporary pharmacological environnementin a contemporary pharmacological environnementin the 7,885 patients with ACS who underwent PCIin the 7,885 patients with ACS who underwent PCIin the OASISin the OASIS--5 trial (TRA or TFA)5 trial (TRA or TFA)
Baseline CharacteristicsBaseline CharacteristicsD hiD hi % %% %
FemoralFemoral(N=7,013)(N=7,013)
RadialRadial(N=872)(N=872)
pp--valuevalue
DemographicsDemographics TFA 89% and TRA 11%TFA 89% and TRA 11%
Endpoint Measures atEndpoint Measures at Day 9Day 9Endpoint Measures atEndpoint Measures at Day 9Day 9OASIS 5: Access site postOASIS 5: Access site post--hoc analysishoc analysis
Endpoint Measures atEndpoint Measures at Day 9Day 9Endpoint Measures atEndpoint Measures at Day 9Day 9Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral
H d tiH d tiH d tiH d ti R di lR di l F lF l HR (95% CI)HR (95% CI)Hazard ratioHazard ratio±±95% CI95% CI
(G d Di b t GPI P i MI Bi k )(G d Di b t GPI P i MI Bi k )Endpoint Measures Endpoint Measures AdjustedAdjustedEndpoint Measures Endpoint Measures AdjustedAdjusted
Major Bleeding atMajor Bleeding at 6 months6 monthsMajor Bleeding atMajor Bleeding at 6 months6 months
Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral05
ard
0.04
0.0
ativ
e H
az0.
03
HR 0.5295% CI [0.34-0.79]p=0.002C
umul
a0.
010.
020.
00
FemoralRadial
Days0 30 60 90 120 150 180
Death/MI/RI atDeath/MI/RI at 6 months6 monthsDeath/MI/RI atDeath/MI/RI at 6 months6 months
Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral15
rd0.
ive
Haz
a0.
10
HR 0.8495% CI [0.69-1.04]p=0.10C
umul
at0.
050.
0
FemoralRadial
Days0 30 60 90 120 150 180
Mortality at 6 MonthsMortality at 6 MonthsMortality at 6 MonthsMortality at 6 MonthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral
Major Bleeding definition:Major Bleeding definition:Clinically overt bleeding that is either fatal, intracranial, retroperitoneal, intraocular, drop in Hb Clinically overt bleeding that is either fatal, intracranial, retroperitoneal, intraocular, drop in Hb ≥≥ 3g/dL 3g/dL or requiring transfusion or requiring transfusion ≥≥ 2U RBC2U RBC
Protocol Major BleedingProtocol Major Bleedingi PCI ti t ti PCI ti t t D 9D 9in PCI patients atin PCI patients at Day 9Day 9
Femoral Radial
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•• In ACS patients undergoing PCI, In ACS patients undergoing PCI, radial accessradial access was associated was associated withwith similar rates of ischemiasimilar rates of ischemia and significantlyand significantly reduced majorreduced majorwith with similar rates of ischemiasimilar rates of ischemia and significantly and significantly reduced major reduced major bleedingbleeding compared with femoral access, leading to compared with femoral access, leading to better net better net clinical outcome.clinical outcome.
•• Our results suggest that TRA by reducing major bleedingOur results suggest that TRA by reducing major bleeding maymayOur results suggest that TRA by reducing major bleeding Our results suggest that TRA by reducing major bleeding may may be associated with 6 months mortality reductionbe associated with 6 months mortality reduction as compared to as compared to TFA.TFA.
•• Randomized trials are warranted to confirm the impact of Randomized trials are warranted to confirm the impact of ppaccess site on eventaccess site on event--free survivalfree survival
•• A fondaparinux strategy:A fondaparinux strategy:R d j bl di b th i f l d di lR d j bl di b th i f l d di l Reduces major bleeding both in femoral and radial accessReduces major bleeding both in femoral and radial access
Improves net clinical outcome in femoral approach Improves net clinical outcome in femoral approach compared to an enoxaparin based regimencompared to an enoxaparin based regimen
Study Design Study Design –– ACUITY TrialACUITY TrialM d tM d t hi h i k t bl i NSTEMIhi h i k t bl i NSTEMIM d tM d t hi h i k t bl i NSTEMIhi h i k t bl i NSTEMIModerateModerate--high risk unstable angina or NSTEMI high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)undergoing an invasive strategy (N = 13,819)
ModerateModerate--high risk unstable angina or NSTEMI high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819)undergoing an invasive strategy (N = 13,819)
72hUFH or
Enoxaparin+ GP IIb/III
Medicalmanagement
Moderate-high risk y
with
in + GP IIb/IIIa
BivalirudinR*
g
high riskACS
iogr
aphy
Aspirin in allAspirin in allAspirin in allAspirin in all
+ GP IIb/IIIaR* PCI
Ang
Aspirin in allAspirin in allClopidogrelClopidogrel
dosing and timingdosing and timingper local practiceper local practice
Aspirin in allAspirin in allClopidogrelClopidogrel
dosing and timingdosing and timingper local practiceper local practice
BivalirudinAlone CABG
*Stratified by pre*Stratified by pre--angiography thienopyridine use or administrationangiography thienopyridine use or administration*Stratified by pre*Stratified by pre--angiography thienopyridine use or administrationangiography thienopyridine use or administration
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75ACUITY Design. Stone GW et al. AHJ 2004;148:764–75
Primary Results by TreatmentPrimary Results by TreatmentPrimary Results by TreatmentPrimary Results by Treatment
UFH/Enox UFH/Enox + GP IIb/IIIa+ GP IIb/IIIa
Bivalirudin +Bivalirudin +GP IIb/IIIaGP IIb/IIIa
BivalirudinBivalirudinalonealone
EndpointEndpoint RateRate RateRate P ValueP Value RateRate P ValueP Value
Net clinical Net clinical outcomeoutcome 11.7%11.7% 11.8%11.8% <0.001 NI<0.001 NI 10.1%10.1% 0.015 0.015
SSoutcomeoutcome 11.7%11.7% 11.8%11.8% 0.001 NI0.001 NI 10.1%10.1% SupSup
Major Major bleedingbleeding 5.7%5.7% 5.3%5.3% 0.001 NI0.001 NI 3.0%3.0% <0.001 <0.001
SupSupNI = non-inferiority; Sup = superiority
Gregg Stone, ACC 2006 Presentation
ACUITY AccessACUITY AccessACUITY AccessACUITY Access450 centers in 17 countries450 centers in 17 countries450 centers in 17 countries450 centers in 17 countries
100% of Radial & Femoral Angiogram Access per country
Endpoint MeasuresEndpoint MeasuresEndpoint MeasuresEndpoint MeasuresRadial vs FemoralRadial vs FemoralRadial vs FemoralRadial vs FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral
Bivalirudin Alone vs. Hep + GPIBivalirudin Alone vs. Hep + GPI 0.630.63 0.52 0.52 –– 0.770.77 <0.001<0.001
Radial vs FemoralRadial vs Femoral 0 470 47 0 310 31 0 720 72 <0 001<0 001Radial vs. FemoralRadial vs. Femoral 0.470.47 0.31 0.31 –– 0.720.72 <0.001<0.001
Medical ManagementMedical Management 0.440.44 0.35 0.35 –– 0.540.54 <0.001<0.001
Conclusions (II)Conclusions (II)
•• In moderate and high risk ACS patients undergoing In moderate and high risk ACS patients undergoing an early invasive strategy, radial access was an early invasive strategy, radial access was associated with similar rates of ischemia and associated with similar rates of ischemia and significantly reduced protocol major bleeding significantly reduced protocol major bleeding compared with femoral accesscompared with femoral accesspp
•• A bivalirudin alone strategy:A bivalirudin alone strategy: Reduces major and minor bleeding in patients withReduces major and minor bleeding in patients with Reduces major and minor bleeding in patients with Reduces major and minor bleeding in patients with
femoral accessfemoral access Results in similar bleeding complications with Results in similar bleeding complications with
femoral compared to radial accessfemoral compared to radial access Provides similar antiProvides similar anti--ischemic protection ischemic protection
compared to UFH/enox + GPIcompared to UFH/enox + GPIcompared to UFH/enox + GPIcompared to UFH/enox + GPI
Identification of Risk Factors For Bleedingin ACS Patients and Preventive actions
Risk Factors For Bleeding in ACS PatientsRisk Factors For Bleeding in ACS Patients
P ti t l t dP ti t l t d P d l l t dP d l l t d T t t l t dT t t l t dPatient relatedPatient related Procedural relatedProcedural related Treatment relatedTreatment related
Female genderFemale genderOlderOlderHypertensionHypertensionObesityObesity or or Low weightLow weightRenal failureRenal failure
Puncture sitePuncture site (femoral vs radial)(femoral vs radial)Level of puncture (femoral)Level of puncture (femoral)Larger arterial sheathLarger arterial sheathProlonged sheath timeProlonged sheath timeIABP placementIABP placement
Over anticoagulationOver anticoagulationType of anticoagulation (antiXa, Type of anticoagulation (antiXa, direct thrombin inhibtor or direct thrombin inhibtor or LMWH and UFH)LMWH and UFH)GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors
Identification
Low platelet count, aneamiaLow platelet count, aneamiaMedical history (GI disease)Medical history (GI disease)
ppConcomitant venous sheathConcomitant venous sheathNeed for repeat interventionNeed for repeat intervention
ThrombolyticThrombolytic
R d i Bl di Ri k P ti A tiR d i Bl di Ri k P ti A tiReducing Bleeding Risk: Preventive ActionsReducing Bleeding Risk: Preventive Actions
Patient information (coughing, Patient information (coughing, heavy lifting to be avoided after heavy lifting to be avoided after femoral puncture)femoral puncture)Nurse training for earlyNurse training for early
Perfect puncture sitePerfect puncture siteAngiographic control before Angiographic control before closure device useclosure device useRADIAL tRADIAL t
ACT during procedures for ACT during procedures for anticoagulation monitorringanticoagulation monitorringDiscontinuation of antithrombin Discontinuation of antithrombin after uncomplicated PCIafter uncomplicated PCI
PreventionNurse training for early Nurse training for early recognition of retroperitoneal recognition of retroperitoneal hemorrhagehemorrhage
RADIAL artery accessRADIAL artery accessDifferent access sites for staged Different access sites for staged proceduresproceduresDecrease size of arterial sheathDecrease size of arterial sheath
Hamon M. et al. EuroIntervention 2007A Systematic Review and Meta-analysis
Entry site complications: Radial vs FemoralMeta-analysis of randomized studies
Pooled Relative Risks of Access site complications Decrease*Pooled Relative Risks of Access site complications Decrease*Random-effects Meta-analysis of 17 Studies
Study Radial Femoral RR (random) RR (random)n/N n/N 95% CI 95% CI
Test for heterogeneity: Chi² = 4.80, df = 16 (P = 1.00), I² = 0%
Test for overall effect: Z = 5.09 (P < 0.00001)
0.001 0.01 0.1 1 10 100 1000
Favours Radial Favours Femoral
Incidence: 0.36% vs 2.9%RR 0.22 [0.12-0.39], 78% reduction
AHA 20063131
Adapted and updated from Agostoni et al J Am Coll Cardiol 2004
Favours Radial Favours FemoralNNT 39
RIVAL TRIAL
ObjectivesTo determine if radial>femoral for reducing major bleedingTo compare ischemic complications (Death MI RI stroke)To compare ischemic complications (Death, MI, RI, stroke)To compare each strategy for duration, amount of contrast, costsTo determine if radial site procedures shorten hospital stays
7000 patients randomised at time of catheterizationFor access: Radial versus FemoralFor access: Radial versus Femoral