OASIS 5 Access AHA 2006 Martial Hamon, Shamir Mehta, Gabriel Steg, David Faxon, Prafulla Kerkar,...

OASIS 5OASIS 5AccessAccess

AHA 2006

Martial HamonMartial Hamon, Shamir Mehta, Gabriel Steg, David , Shamir Mehta, Gabriel Steg, David Faxon, Prafulla Kerkar, Hans-Jürgen Rupprecht, Faxon, Prafulla Kerkar, Hans-Jürgen Rupprecht,

Jean-Francois Tanguay, Rizwan Afzal, Salim YusufJean-Francois Tanguay, Rizwan Afzal, Salim YusufOn behalf of the Oasis 5 investigatorsOn behalf of the Oasis 5 investigators

Major bleeding in patients with acute Major bleeding in patients with acute coronary syndrome undergoing early coronary syndrome undergoing early

invasive management can be reduced by invasive management can be reduced by fondaparinux, even in the context of fondaparinux, even in the context of trans-radial coronary intervention: trans-radial coronary intervention:

Insights from OASIS-5 Trial.Insights from OASIS-5 Trial.

OASIS 5OASIS 5

FondaparinuxFondaparinux::

AT AT AT Xa Xa

II IIa THROMBIN

Fibrinogen Fibrin

Fondaparinux

Antithrombin

Intrinsic pathway

Extrinsicpathway

Synthetic pentasaccharideSynthetic pentasaccharidePure factor Xa inhibitorPure factor Xa inhibitorSelective binding to antithrombinSelective binding to antithrombinRapid and predictable inhibition of factor XaRapid and predictable inhibition of factor Xa

OASIS-5OASIS-5

20,078 patients with Non ST-ACS

2 of 3 criteria : Age > 60. Δ ST. rise of biol. makers

Fondaparinux2.5 mg / d

Randomization

Enoxaparin1 mg/kg X 2/d

PEP:• Efficacy : death, MI, refract. Ischemia @ day 9• Safety : major bleeding• Net clinical outcome : death, MI, refract. Ischemia, major bleeding

Secondary EP: Individual PEP (death) @ day30 & day180 Hypothesis : non-inferiority test then superiority test

ASA. Clopidogrel. GP IIb/IIla IV

Primary Endpoint OASIS 5Primary Endpoint OASIS 5Death/MI/RI day 9Death/MI/RI day 9

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0 1 2 3 4 5 6 7 8 90.0

0.01

0.02

0.03

0.04

0.05

0.06

NS

Days from randomization

FondaparinuxEnoxaparin

N Engl J Med 2006;354:1464-76

Major bleeding at Major bleeding at day 9day 9

0 1 2 3 4 5 6 7 8 9

0.0

0.01

0.02

0.03

0.04


Enoxaparin

Fondaparinux

HR 0.53IC 95% 0.45-0.62

p << 0.00001

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N Engl J Med 2006;354:1464-76

Net clinical outcome at Net clinical outcome at Day 9Day 9

Enoxaparin

Fondaparinux

HR 0.82IC 95 % 0.74-0.90

p << 0.00001

0 1 2 3 4 5 6 7 8 9

0.0

0.02

0.04

0.06

0.08


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N Engl J Med 2006;354:1464-76

Death through day 30

Mortality at Mortality at Day 30Day 30

N Engl J Med 2006;354:1464-76

BackgroundBackground

• The use of The use of combined antithrombotic therapiescombined antithrombotic therapies and routine and routine invasive proceduresinvasive procedures in in ACSACS has has decreased the risk of ischemic decreased the risk of ischemic eventsevents substantially but remains associated with a significant substantially but remains associated with a significant increase in bleeding risk.increase in bleeding risk.

• Recently Recently FondaparinuxFondaparinux in the OASIS 5 trial has been shown to in the OASIS 5 trial has been shown to be a preferred alternative to enoxaparin in this setting because it be a preferred alternative to enoxaparin in this setting because it preserves efficacy and preserves efficacy and by significantly reducing major bleeding by significantly reducing major bleeding provides for better long-term event-free survival.provides for better long-term event-free survival.

• The impact of a The impact of a trans-radial approachtrans-radial approach to percutaneous coronary to percutaneous coronary intervention (PCI) on intervention (PCI) on efficacy and bleeding in ACSefficacy and bleeding in ACS patients patients treated treated with a contemporary pharmacological regimenwith a contemporary pharmacological regimen remains remains unknown.unknown.

ObjectivesObjectives

The aim of this post hoc analysis was to examine The aim of this post hoc analysis was to examine the the impact of the trans-radial approachimpact of the trans-radial approach (TRA), in (TRA), in comparison to the trans-femoral approach (TFA) on comparison to the trans-femoral approach (TFA) on PCI-related:PCI-related:

- 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 OASIS-5 trial (TRA or TFA)in the OASIS-5 trial (TRA or TFA)

Patient selection-MethodsPatient selection-Methods

Analyses include all patients who underwent PCI (Brachial access excluded).

Hazard ratio and two sided 95% CI were calculated with use of a cox proportional-hazards model with the access site as the only covariate (day 9, day 30 and at 6 months Fup)

Rates presented are Kaplan-Meier rates.

Adjusted Hazard ratio have also been calculated.

Major Bleeding definition:Clinically overt bleeding that is either fatal, intracranial,retroperitoneal, intraocular, drop in Hb ≥≥ 3g/dLor requiring transfusion ≥≥ 2U RBC

Baseline CharacteristicsBaseline Characteristics

FemoralFemoral

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

RadialRadial

(N=872)(N=872)p-valuep-value

MaleMale 68.8% 74.5% 0.001

DiabetesDiabetes 23.8% 20.4% 0.025

Heart FailureHeart Failure 7.9% 6.2% 0.079

Prior MIPrior MI 23.1% 18.0% <0.001

Prior PCIPrior PCI 15.7% 14.2% 0.260

Prior CABGPrior CABG 9.5% 3.9% <0.001

DemographicsDemographics

FemoralFemoral

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

RadialRadial


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

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

High Risk FeaturesHigh Risk Features

TFA 89% and TRA 11%TFA 89% and TRA 11%

Baseline CharacteristicsBaseline Characteristics

FemoralFemoral

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

RadialRadial


ASAASA 98.6%98.6% 98.4%98.4% 0.7010.701

ClopidogrelClopidogrel 85.6%85.6% 88.0%88.0% 0.0620.062

GPIIb/IIIa InhibitorGPIIb/IIIa Inhibitor 32.5%32.5% 43.8%43.8% <0.001<0.001

BetablockerBetablocker 89.2%89.2% 89.0%89.0% 0.8170.817

ACE inhibitorACE inhibitor 68.9%68.9% 60.4%60.4% <0.001<0.001

ARBARB 7.6%7.6% 9.2%9.2% 0.0920.092

StatinsStatins 83.9%83.9% 86.4%86.4% 0.0660.066

Other Lipid lower Other Lipid lower agentsagents 3.3%3.3% 2.3%2.3% 0.1170.117

In Hospital Medications

Procedural DetailsProcedural Details

FemoralFemoral

10048 lesions10048 lesions

RadialRadial

1268 lesions1268 lesions

p-valuep-value

Complete successComplete success 91.6%91.6% 92.4%92.4% 0.3310.331

StentStent 84.4%84.4% 86.2%86.2% 0.1030.103

Bare stentBare stent 62.0%62.0% 61.6%61.6% 0.7980.798

Drug eluting stentDrug eluting stent 22.5%22.5% 24.6%24.6% 0.0890.089

No stentNo stent 15.4%15.4% 13.3%13.3% 0.0490.049

Angio thrombus pre-pciAngio thrombus pre-pci 13.0%13.0% 13.2%13.2% 0.8710.871

Percutaneous coronary interventions(analysis per lesion)

Endpoint Measures atEndpoint Measures at Day 9Day 9Endpoint Measures atEndpoint Measures at Day 9Day 9Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

10.5%8.4% 0.79 (0.62-1.00) 0.05

0 1 2

Hazard ratioHazard ratio±95% CI±95% CI

Hazard ratioHazard ratio±95% CI±95% CIEndpointEndpoint

Net clinical outcome

Death/MI/RI

Major bleeding

Radial betterRadial better Femoral betterFemoral better

RadialRadial(n=872)(n=872)

FemoralFemoral(n=7013)(n=7013)

HR (95% CI)HR (95% CI)p-valuep-value

7.7%7.1% 0.92 (0.70-1.19) 0.52

3.5%1.6% 0.45 (0.26-0.77)0.004

Days

0.0

0.02

0.04

0.06

0.08

0 1 2 3 4 5 6 7 8 9

Femoral

Radial

Death/MI/RI at Death/MI/RI at Day 9Day 9Death/MI/RI at Death/MI/RI at Day 9Day 9Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.9295% CI [0.70-1.19]p=0.52

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HR 0.4595% CI [0.26-0.77]p=0.004

Major Bleeding atMajor Bleeding at Day 9Day 9Major Bleeding atMajor Bleeding at Day 9Day 9Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

Days

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0.0

0.01

0.02

0.03

0 1 2 3 4 5 6 7 8 9

Femoral

Radial

Net clinical outcome atNet clinical outcome at Day 9Day 9Net clinical outcome atNet clinical outcome at Day 9Day 9Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.7995% CI [0.62-1.00]p=0.05

Days

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0.0

0.0

20

.04

0.0

60

.08

0.1

0

0 1 2 3 4 5 6 7 8 9

Femoral

Radial

Endpoint Measures atEndpoint Measures at Day 30Day 30Endpoint Measures atEndpoint Measures at Day 30Day 30Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

13.1%10.3% 0.78 (0.62-0.96)0.021

0 1 2




Death/MI/RI

Major bleeding





10.0%8.9% 0.89 (0.70-1.12)0.316

4.1%2.1% 0.50 (0.31-0.80)<0.004

Death/MI/RI atDeath/MI/RI at Day 30Day 30Death/MI/RI atDeath/MI/RI at Day 30Day 30Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.8995% CI [0.70-1.12]p=0.31

Days

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0.0

0.02

0.04

0.06

0.08

0.10

0 3 6 9 12 15 18 21 24 27 30

Femoral

Radial

Major Bleeding atMajor Bleeding at Day 30Day 30Major Bleeding atMajor Bleeding at Day 30Day 30Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.5095% CI [0.31-0.80]p=0.004

Days

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0.0

0.01

0.02

0.03

0.04

0 3 6 9 12 15 18 21 24 27 30

Femoral

Radial

Net clinical outcome atNet clinical outcome at Day 30Day 30Net clinical outcome atNet clinical outcome at Day 30Day 30Radial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.7895% CI [0.62-0.96]p=0.021

Days

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0.0

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0 3 6 9 12 15 18 21 24 27 30

Femoral

Radial

Endpoint Measures atEndpoint Measures at 6 months6 monthsEndpoint Measures atEndpoint Measures at 6 months6 monthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

17.5%13.5% 0.76 (0.63-0.92)

0 1 2

0.005




Death/MI/RI

Major bleeding





13.9%11.8% 0.84 (0.69-1.04)0.103

5.1%2.7% 0.52 (0.34-0.79)0.002

Death/MI/RI atDeath/MI/RI at 6 months6 monthsDeath/MI/RI atDeath/MI/RI at 6 months6 monthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.8495% CI [0.69-1.04]p=0.10

Days

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0.0

0.05

0.10

0.15

0 30 60 90 120 150 180

Femoral

Radial

Major Bleeding atMajor Bleeding at 6 months6 monthsMajor Bleeding atMajor Bleeding at 6 months6 monthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.5295% CI [0.34-0.79]p=0.002

Days

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00.

010.

020.

030.

040.

05

0 30 60 90 120 150 180

Femoral

Radial

Net clinical outcome atNet clinical outcome at 6 months6 monthsNet clinical outcome atNet clinical outcome at 6 months6 monthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.76 (adjusted)95% CI [0.63-0.92]p=0.005

Days

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00.

050.

100.

15

0 30 60 90 120 150 180

Femoral

Radial

Mortality atMortality at 6 months6 monthsMortality atMortality at 6 months6 monthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.6895% CI [0.43-1.07]p=0.09

Days

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00.

010.

020.

03

0 30 60 90 120 150 180

Femoral

Radial

Protocol Major BleedingProtocol Major Bleedingin PCI patients atin PCI patients at Day 9Day 9

3,5%

4,8%

2,3%

0,9%1,6%

2,4%

Overall Enoxaparin Fondaparinux

9 d

ay e

ven

ts (

%)

Femoral Radial

P =0.03 P=0.026 P =0.048

(during blind study drug administration)

Protocol Major BleedingProtocol Major Bleedingat at Day 9Day 9

(during blind study drug administration)

2,4%

4,8%

0,9%

2,3%

Radial Femoral

9 d

ay

ev

en

ts (

%)

Enoxaparin Fondaparinux

P = 0.08 P = <0.0001

(N=416) (N=456) (N=3,523) (N=3,490)

HR 0.3695% CI [0.11-1.16]

HR 0.4895% CI [0.37-0.62]

Protocol Major BleedingProtocol Major BleedingEnoxaparin versus FondaparinuxEnoxaparin versus FondaparinuxEnoxaparin versus FondaparinuxEnoxaparin versus Fondaparinux

0 1 2

Fondaparinux Enoxaparin

Enox. Fonda. P Pint

0.654.8% 2.3% 0.48 (0.37-0.62) <0.001

2.4% 0.9% 0.36 (0.11-1.16) 0.086

0.375.2% 3.0% 0.56 (0.44-0.72) <0.001

3.1% 1.1% 0.35 (0.12-0.98) 0.045

0.316.1% 4.0% 0.64 (0.51-0.79) <0.0013.9% 1.5% 0.39 (0.16-0.96) 0.040

HR (95% CI)

Femoral (n=7013)

Radial (n=872)

Femoral (n=7013)

Radial (n=872)

Major Bleed day 180

Femoral (n=7013)

Radial (n=872)

Hazard Ratio±95% CI

Hazard Ratio±95% CI

Major Bleed day 9

Major Bleed day 30

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

FemoralFemoral

(N=7013)(N=7013)

RadialRadial


Major BleedMajor Bleed 3.5%3.5% 1.6%1.6% 0.0020.002

Retroperitoneal Hem.Retroperitoneal Hem. 0.3%0.3% 0%0% 0.1240.124

PseudoaneurysmPseudoaneurysm 1.2%1.2% 0%0% 0.0010.001

Large hematomaLarge hematoma 3.1%3.1% 0.3%0.3% <0.001<0.001

GI BleedingGI Bleeding 0.5%0.5% 0%0% 0.0420.042

Other siteOther site 2.8%2.8% 1.6%1.6% 0.0380.038

Hb drop Hb drop ≥≥ 3g/dL 3g/dL 2.8%2.8% 1.1%1.1% 0.0040.004

Hb dop Hb dop ≥≥ 5 g/dL 5 g/dL 1.1%1.1% 0.5%0.5% 0.0820.082

Blood transfusionBlood transfusion 3.6%3.6% 1.5%1.5% 0.0010.001

Blood transfusion >2 UBlood transfusion >2 U 2.3%2.3% 0.6%0.6% 0.0010.001

Radial versus FemoralRadial versus 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 or requiring transfusion 3g/dL or requiring transfusion ≥≥ 2U RBC 2U RBC

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

Endpoint Measures Endpoint Measures AdjustedAdjustedEndpoint Measures Endpoint Measures AdjustedAdjusted

FemoralbetterFemoralbetter

EndpointEndpoint


Death/MI/RI

Majorbleeding

RadialbetterRadialbetter


0 1 2



0 1 2





0 1 2




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

P=0.03

P=0.36

P=0.003

P=0.02

P=0.31

P=0.003

P=0.009

P=0.18

P=0.002

FemoralFemoral

(N=7013)(N=7013)

RadialRadial


Day 9 Day 9

Net clinical outcomeNet clinical outcome 10.5%10.5% 8.4%8.4% 0.0300.030

Death/MI/RIDeath/MI/RI 7.7%7.7% 7.1%7.1% 0.3640.364


Day 30 Day 30




Day 180 Day 180




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

Endpoint Measures Endpoint Measures AdjustedAdjustedEndpoint Measures Endpoint Measures AdjustedAdjusted

At 6 monthsAt 6 months NNTNNT

Net clinical outcomeNet clinical outcome 2525

Death/MI/RIDeath/MI/RI 4848

Major BleedMajor Bleed 4242

Mortality at 6 MonthsMortality at 6 MonthsMortality at 6 MonthsMortality at 6 MonthsRadial vs. FemoralRadial vs. FemoralRadial vs. FemoralRadial vs. Femoral

HR 0.6895% CI [0.43-1.07]p=0.09

DaysDays

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dC

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Haz

ard

0.0

0.01

0.02

0.03

0 30 60 90 120 150 180

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

3.4%

2.3%

NNT~100NNT~100Femoral

Radial

ConclusionsConclusions

• In ACS patients undergoing PCI, In ACS patients undergoing PCI, radial accessradial access was was associated with associated with similar rates of ischemiasimilar rates of ischemia and significantly and significantly reduced major bleedingreduced major bleeding compared with femoral access, compared with femoral access, leading to leading to better net clinical outcome.better net clinical outcome.

• Our results suggest that TRA by reducing major bleeding Our results suggest that TRA by reducing major bleeding may be associated with 6 months mortality reductionmay be associated with 6 months mortality reduction as as compared to TFA.compared to TFA.

• Randomized trials are warranted to confirm the impact of Randomized trials are warranted to confirm the impact of access site on event-free survivalaccess site on event-free survival

• A fondaparinux strategy:A fondaparinux strategy: Reduces major bleeding both in femoral and radial Reduces major bleeding both in femoral and radial

accessaccess 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

AcknowledgementsAcknowledgements

Shamir Metha and Salim YusufShamir Metha and Salim Yusuf Rizwan Afzal (statistical analysis)Rizwan Afzal (statistical analysis)

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OASIS 5 Access AHA 2006 Martial Hamon, Shamir Mehta, Gabriel Steg, David Faxon, Prafulla Kerkar,...

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