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%

( , )( , ) ( )( )

MaleMale 68.8% 74.5% 0.001DiabetesDiabetes 23.8% 20.4% 0.025Heart FailureHeart Failure 7.9% 6.2% 0.079Prior MIPrior MI 23.1% 18.0% <0.001Prior PCIPrior PCI 15.7% 14.2% 0.260Prior CABGPrior CABG 9.5% 3.9% <0.001

F lF l R di lR di l

High Risk FeaturesHigh Risk FeaturesFemoralFemoral

(N=7,013)(N=7,013)RadialRadial

(N=872)(N=872)pp--valuevalue

Biomarker +Biomarker + 77.3%77.3% 82.5%82.5% 0.0010.001

ST ST dep. > 1mmdep. > 1mm 43.0%43.0% 40.3%40.3% 0.1170.117

Baseline CharacteristicsBaseline CharacteristicsIn Hospital Medications

FemoralFemoral(N=7,013)(N=7,013)

RadialRadial(N=872)(N=872)

pp--valuevalue

ASAASA 98 6%98 6% 98 4%98 4% 0 7010 701ASAASA 98.6%98.6% 98.4%98.4% 0.7010.701ClopidogrelClopidogrel 85.6%85.6% 88.0%88.0% 0.0620.062GPIIb/IIIa InhibitorGPIIb/IIIa Inhibitor 32.5%32.5% 43.8%43.8% <0.001<0.001BetablockerBetablocker 89.2%89.2% 89.0%89.0% 0.8170.817ACE inhibitorACE inhibitor 68.9%68.9% 60.4%60.4% <0.001<0.001ARBARB 7.6%7.6% 9.2%9.2% 0.0920.092StatinsStatins 83.9%83.9% 86.4%86.4% 0.0660.066Other Lipid lower agentsOther Lipid lower agents 3.3%3.3% 2.3%2.3% 0.1170.117

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

Hazard ratioHazard ratio±±95% CI95% CIEndpointEndpoint

RadialRadial(n=872)(n=872)

FemoralFemoral(n=7013)(n=7013)

HR (95% CI)HR (95% CI) pp--valuevalue

10.5%8.4% 0.79 (0.62-1.00) 0.05Net clinical outcome

Death/MI/RI

Major bleeding

7.7%7.1% 0.92 (0.70-1.19) 0.52

3 5%1 6% 0 45 (0 26-0 77) 0 004

0 1 2

Major bleeding 3.5%1.6% 0.45 (0.26-0.77) 0.004

0 1 2

Radial betterRadial better Femoral betterFemoral better

(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

(Gender, Diabetes, GPI, Prior MI, Biomarkers)(Gender, Diabetes, GPI, Prior MI, Biomarkers)

Day 9Day 9 Day 30Day 30 Day 180Day 180

EndpointEndpointHazard ratioHazard ratio

±±95% CI95% CIHazard ratioHazard ratio

±±95% CI95% CIHazard ratioHazard ratio

±±95% CI95% CIHazard ratioHazard ratio

±±95% CI95% CIHazard ratioHazard ratio

±±95% CI95% CIHazard ratioHazard ratio

±±95% CI95% CI

Net clinical outcome

P=0.03 P=0.02 P=0.009

Death/MI/RI

Major

P=0.36

P=0 003

P=0.31

P=0 003

P=0.18

P=0 002jbleeding

0 1 2 0 1 2 0 1 2

P=0.003 P=0.003 P=0.002

FemoralbetterFemoralbetter

0 1 2RadialbetterRadialbetter

0 1 2RadialbetterRadialbetter

FemoralbetterFemoralbetter

0 1 2RadialbetterRadialbetter

FemoralbetterFemoralbetter

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

ard

ard

0.03

3.4%

ativ

e H

aza

ativ

e H

aza

0.02 2.3%

HR 0.6895% CI [0.43-1.07]p=0 09

Cum

ula

Cum

ula

0.01

NonNon--adjusted: HR 0.68 [0.43adjusted: HR 0.68 [0.43--1.07] p=0.091.07] p=0.09Adjusted: HR 0.71 [0.45Adjusted: HR 0.71 [0.45--1.13] p=0.151.13] p=0.15p=0.09

0.0

j [j [ ] p] p

NNT~100NNT~100FemoralRadial

DaysDays

0 30 60 90 120 150 180

Bleeding & Access complicationsBleeding & Access complications at Day 9at Day 9

FemoralFemoral(N=7013)(N=7013)

RadialRadial(N=872)(N=872)

pp--valuevalue

Radial versus FemoralRadial versus Femoral

(N=7013)(N=7013) (N=872)(N=872)

Major BleedMajor Bleed 3.5%3.5% 1.6%1.6% 0.0020.002Retroperitoneal Hem.Retroperitoneal Hem. 0.3%0.3% 0%0% 0.1240.124PseudoaneurysmPseudoaneurysm 1.2%1.2% 0%0% 0.0010.001Large hematomaLarge hematoma 3.1%3.1% 0.3%0.3% <0.001<0.001GI BleedingGI Bleeding 0.5%0.5% 0%0% 0.0420.042gg %% %%Other siteOther site 2.8%2.8% 1.6%1.6% 0.0380.038Hb drop Hb drop ≥≥ 3g/dL3g/dL 2.8%2.8% 1.1%1.1% 0.0040.004Hb dopHb dop ≥≥ 5 g/dL5 g/dL 1 1%1 1% 0 5%0 5% 0 0820 082Hb dop Hb dop ≥≥ 5 g/dL5 g/dL 1.1%1.1% 0.5%0.5% 0.0820.082Blood transfusionBlood transfusion 3.6%3.6% 1.5%1.5% 0.0010.001Blood transfusion >2 UBlood transfusion >2 U 2.3%2.3% 0.6%0.6% 0.0010.001

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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(%)

Femoral Radial

P =0.03 P=0.026 P =0.048

3 5%

4,8%

y ev

ents

3,5%

2,3%1,6%

2,4%9 da

y

0,9%

O ll E i F d iOverall Enoxaparin Fondaparinux

(during blind study drug administration)

(Gender, Diabetes, GPI, Prior MI, Biomarkers)(Gender, Diabetes, GPI, Prior MI, Biomarkers)Endpoint Measures Endpoint Measures AdjustedAdjustedEndpoint Measures Endpoint Measures AdjustedAdjusted

FemoralFemoral(N=7013)(N=7013)

RadialRadial(N=872)(N=872)

pp--valuevalue

( , , , , )( , , , , )

( )( ) ( )( )

Day 9 Day 9 Net clinical outcomeNet clinical outcome 10.5%10.5% 8.4%8.4% 0.0300.030At 6 monthsAt 6 months NNTNNTDeath/MI/RIDeath/MI/RI 7.7%7.7% 7.1%7.1% 0.3640.364Major BleedMajor Bleed 3.5%3.5% 1.6%1.6% 0.0030.003Day 30 Day 30

Net clinical outcomeNet clinical outcome 2525

Net clinical outcomeNet clinical outcome 13.1%13.1% 10.3%10.3% 0.0190.019Death/MI/RIDeath/MI/RI 10.0%10.0% 8.9%8.9% 0.3110.311Major BleedMajor Bleed 4.1%4.1% 2.1%2.1% 0.0030.003

Death/MI/RIDeath/MI/RI 4848

Major BleedMajor Bleed 4242Major BleedMajor Bleed 4.1%4.1% 2.1%2.1% 0.0030.003Day 180 Day 180 Net clinical outcomeNet clinical outcome 17.5%17.5% 13.5%13.5% 0.0090.009Death/MI/RIDeath/MI/RI 13 9%13 9% 11 8%11 8% 0 1800 180Death/MI/RIDeath/MI/RI 13.9%13.9% 11.8%11.8% 0.1800.180Major BleedMajor Bleed 5.1%5.1% 2.7%2.7% 0.0020.002

Conclusions (I)Conclusions (I)

•• 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

Ischemic Ischemic eventsevents 7.3%7.3% 7.7%7.7% 0.007 NI0.007 NI 7.8%7.8% 0.011 NI0.011 NIeventsevents

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

70

80

90

50

60

70

20

30

40

0

10

orway

rance

eden UK

inland

mark Italy

anad

a

Spain NZ

lgium

many

USA

strali

a

Nor Fra

Swe Fin

Denm

Can Sp

Belg

Germ Austr

Radial (798) 11988 Femoral

Baseline CharacteristicsBaseline CharacteristicsBaseline CharacteristicsBaseline CharacteristicsRadialRadial

(N=798)(N=798)FemoralFemoral

(N=11,988)(N=11,988)pp--valuevalue

Age Age (yrs)(yrs) 62 62 ±± 1212 63 63 ±± 1212 0.0160.016Weight (kg)Weight (kg) 82 82 ±± 1919 85 85 ±± 1818 <0.001<0.001MaleMale 76 4%76 4% 69 5%69 5% <0 001<0 001MaleMale 76.4%76.4% 69.5%69.5% <0.001<0.001DiabetesDiabetes 21.3%21.3% 27.8%27.8% <0.001<0.001HypertensionHypertension 51.3%51.3% 67.8%67.8% <0.001<0.001H li id iH li id i 45 1%45 1% 57 9%57 9% <0 001<0 001HyperlipidemiaHyperlipidemia 45.1%45.1% 57.9%57.9% <0.001<0.001Current smokerCurrent smoker 31.2%31.2% 28.9%28.9% 0.1740.174Prior MIPrior MI 25.4%25.4% 31.5%31.5% <0.001<0.001Prior PCIPrior PCI 23.1%23.1% 39.7%39.7% <0.001<0.001Prior CABGPrior CABG 5.5%5.5% 18.5%18.5% <0.001<0.001Renal insufficiency*Renal insufficiency* 18.2%18.2% 19.0%19.0% 0.6190.619yy

* CrCl < 60 mL/min

Baseline High Risk FeaturesBaseline High Risk FeaturesBaseline High Risk FeaturesBaseline High Risk Features

RadialRadial(N=798)(N=798)

FemoralFemoral(N=11 988)(N=11 988) pp--valuevalue(N 798)(N 798) (N 11,988)(N 11,988)

Biomarker or ST Biomarker or ST 84.8%84.8% 71.7%71.7% <0.0001<0.0001

Biomarker +Biomarker + 70 8%70 8% 59 0%59 0% <0 0001<0 0001Biomarker +Biomarker + 70.8%70.8% 59.0%59.0% <0.0001<0.0001

Endpoint MeasuresEndpoint MeasuresEndpoint MeasuresEndpoint MeasuresRadial vs FemoralRadial vs FemoralRadial vs FemoralRadial vs FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

Risk ratio±95% CI

Risk ratio±95% CIEndpoint

Radial(n=798)

Femoral(n=11 988)

OR (95% CI)adjusted p-value

11 1%10 5% 0 95 (0 77-1 17) 0 62

±95% CI±95% CI

Net clinical

(n 798) (n 11,988) adjusted

11.1%10.5% 0.95 (0.77-1.17) 0.62outcome

Ischemic composite 7.4%8.1% 1.10 (0.86-1.40) 0.45p

Major bleeding 4.8%3.0% 0.63 (0.42-0.95) 0.02

0 1 2

Radial betterRadial better Femoral betterFemoral betterRadial betterRadial better Femoral betterFemoral better

Protocol Major BleedingProtocol Major Bleeding –– NonNon--CABGCABGProtocol Major Bleeding Protocol Major Bleeding NonNon CABGCABG

Radial Femoral

P = 0.01 P = 0.06 P = 0.29

s (%

)

Radial (n=798)

Femoral (n=11,988)

ay e

vent

s

2 2% 2 7%4,2%

3 0%

5,8% 5,4%30 d

a

2,2% 2,7% 3,0%

UFH/ GPI Bi GPI Bi AlUFH/enox + GPI Biv + GPI Biv Alone

Net Clinical Outcome Composite EndpointNet Clinical Outcome Composite EndpointRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

FemoralFemoral

Radial

s (%

)

Radial

ve E

vent

sC

umul

ati

D f R d i tiDays from Randomization

Ischemic Composite EndpointIschemic Composite EndpointIschemic Composite EndpointIschemic Composite EndpointRadial vs. FemoralRadial vs. Femoral

s (%

)

F l

Radial

ve E

vent

s Femoral

Cum

ulat

i

D f R d i tiDays from Randomization

Major Bleeding EndpointMajor Bleeding EndpointRadial vs.Radial vs. FemoralFemoralRadial vs.Radial vs. FemoralFemoral

Femoral

ts (%

)

Femoral

tive

Even

t

Radial

Cum

ulat

Days from Randomization

Multivariate ModelMultivariate Model –– Any TIMI BleedingAny TIMI BleedingMultivariate Model Multivariate Model Any TIMI BleedingAny TIMI Bleeding

VariableVariable EstimateEstimate RangeRange pp--valuevalueVariableVariable gg pp

CrCl < 60CrCl < 60 1.711.71 1.40 1.40 –– 2.092.09 <0.001<0.001

Significant Coronary DiseaseSignificant Coronary Disease 1.561.56 1.31 1.31 –– 1.861.86 <0.001<0.001

Age ≥ 75Age ≥ 75 1.491.49 1.22 1.22 –– 1.831.83 <0.001<0.001

ECG ChangesECG Changes 1.291.29 1.10 1.10 –– 1.521.52 0.0020.002

HypertensionHypertension 1.241.24 1.03 1.03 –– 1.491.49 0.020.02

Bivalirudin + GPI vs. Hep + GPIBivalirudin + GPI vs. Hep + GPI 0.950.95 0.79 0.79 –– 1.131.13 <0.001<0.001

Prior CABGPrior CABG 0.900.90 0.72 0.72 –– 1.131.13 0.370.37

CABGCABG 0.740.74 0.58 0.58 –– 0.950.95 <0.001<0.001

HyperlipidemiaHyperlipidemia 0.700.70 0.59 0.59 –– 0.830.83 <0.001<0.001

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 levelPatient level Procedural levelProcedural level Treatment levelTreatment level

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

after uncomplicated PCIafter uncomplicated PCINew antcioagulation agentsNew antcioagulation agents(Bivalirudin, fondaparinux)(Bivalirudin, fondaparinux)

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

ACCESS 0/300 6/300 0.08 [0.00, 1.36] Achembach 0/152 4/155 0.11 [0.01, 2.09] BRAFE Stent 1/56 3/56 0 33 [0 04, 3 11]BRAFE Stent 1/56 3/56 0.33 [0.04, 3.11] CARAFE 0/140 2/70 0.10 [0.00, 2.07] FARMI 2/57 11/57 0.18 [0.04, 0.78] Gorge 1/214 1/216 1.01 [0.06, 16.03] Grinfeld 0/138 3/141 0.15 [0.01, 2.80] Mann 1996 0/76 4/76 0.11 [0.01, 2.03] Mann 1998 0/74 3/68 0.13 [0.01, 2.50] Moriyama 0/108 3/92 0.12 [0.01, 2.33] OCTOPLUS 3/192 12/185 0.24 [0.07, 0.84] OUTCLAS 0/322 1/322 0.33 [0.01, 8.15] RADIAL-AMI 1/25 1/25 1.00 [0.07, 15.12] RADIAMI 0/50 3/50 0.14 [0.01, 2.70] Reddy 0/25 1/50 0.65 [0.03, 15.50] TEMPURA 0/77 2/72 0.19 [0.01, 3.83] Tian 0/189 2/195 0.21 [0.01, 4.27]

Total (95% CI) 8/2195 62/2130 0.22 [0.12, 0.39]

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