1

Incidence, impact and preventative strategies for non-access site bleeding

in the PCI patient

Martial Hamon. MD. FESCUniversity Hospital. Caen. France

Vas

cula

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om

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ns

(%)

0

1

2

3

4

5

6

7

8

9

Group 1 Group 2 Group 31994-95 1996-99 2000-05

P<0.001For trend

Doyle BJ et al. JACC Intervention 2008;1:202-209.

Changing Incidence from the earliest (8.4%)to the contemporary time period (3.5%)

Doyle BJ et al. JACC Intervention 2008;1:202-209.

Major Femoral BleedingComplications After PCI

Impacton Survival

Jolly S et al. Am Heart J 2009

Meta-analysis of 18 Randomized Trials

Radial vs Femoral AccessImpact on Major Bleeding

RADIAL VS FEMORAL

Favours RADIAL Favours FEMORALMajor Bleeding: 0.54% vs 2.32%

(5 had no bleeding events) 4.458 patients

Death,MI or StrokeMeta-analysis of Randomized Trials

Radial vs Femoral AccessImpact on Ischemic Outcomes

Jolly S et al. Am Heart J 2009

RADIAL VS FEMORAL

Favours RADIAL Favours FEMORALTrend for reduction in composite

of death.MI. stroke(2.5% vs 3.8%. P = .06)

Endpoint Measures at Day 30

Endpoint Measures at Day 30

Radial vs. FemoralRadial vs. Femoral

11.1%10.5% 0.95 (0.77-1.17) 0.62

0 1 2

Risk ratio±95% CI

Risk ratio±95% CIEndpoint

Net clinical outcome

Ischemic composite

Major bleeding

Radial betterRadial better Femoral betterFemoral better

Radial(n=798)

Femoral(n=11.988)

OR (95% CI)adjusted

p-value

7.4%8.1% 1.10 (0.86-1.40) 0.45

4.8%3.0% 0.63 (0.42-0.95) 0.02

ACUITY

7

ACUITY: Femoral vs. Radial AccessMajor or Minor Organ Bleeding

Hamon M. Rasmussen LH. Manoukian SV. et al. EuroIntervention 2009.

0

5

10

Femoral Radial

Heparin+GPI Bivalirudin

Major or minor organ bleeding were reduced to a similar extent in patients treated with bivalirudin alone compared to heparin plus a GPI and were

present with both femoral access (4.1% vs 7.4% respectively. p<0.0001) and radial access (4.9% vs 7.2% respectively. p=0.26).

7.4% 4.1% 7.2% 4.9%

8

0.67 1.2

3.7

5.9

3.13.7

0

1

2

3

4

5

6

7

ACUITY 30 Days

TRITON 3 Days

EARLY ACS 120 hours

SYNERGY 30 Days

OASIS 5 9 days

ABOARD 30 Days

Early Non-CABG Major Bleeding in ACS Trials in PCI-Treated Patients

88% FemoralAccess

84% RadialAccess

Percent Protocol Major Bleed

9

Bleeding definitions

Variation in definitions

Intracranial hemorrhage

Retroperitoneal hemorrhage

Bleeding with 5g/dL fall in hemoglobin

Bleeding with 3g/dL fall in hemoglobin

4g/dL fall in hemoglobin without site

Blood transfusion 3 units

TIMI Major

TIMI Minor

Gross hematuria or hematemesis

Lincoff et al. JAMA 2003

Beyond Access Site Bleeding: Incidence, Sources, and Impact

of Antithrombotic Therapy in the PCI Patient

A Combined Analysis of 17,393 Patients REPLACE-2, ACUITY and HORIZONS-AMI

Freek W.A. Verheugt, Steven R. Steinhubl, Martial Hamon, Harald Darius, Ph. Gabriel Steg, Marco Valgimigli, Steven

P. Marso, Sunil V. Rao, Anthony H. Gershlick.

Onze Lieve Vrouwe Gasthuis, Amsterdam

Bleeding Definitions - 30-day Endpoint

1. Protocol Major (different between REPLACE-2 and ACUITY, HORIZONS)

2. TIMI Major

3. TIMI Minor

4. TIMI Major + Minor

Purpose

1. To identify the incidence and source of bleeding events unrelated to access site among over 17,300 patients undergoing a PCI for a wide variety of clinical diagnoses.

2. Evaluate the impact of antithrombotic therapy (bivalirudin versus heparin + GPIIb/IIIa antagonist) on the occurrence of bleeding unrelated to the access site.

Analysis Population:All PCI patients (ITT) from:

REPLACE-2 N = 6,002

ACUITY N = 7,789

HORIZONS N = 3,602

Total N = 17,393*

* For primary antithrombotic comparisons the GPIIb/IIIa antagonist + bivalirudin arm (n=2609) of ACUITY was excluded, leaving a total of 14,784 patients.

Patient Demographics – N=17,393Age (years)

Age ≥ 75 years (%)

Weight (kg)

Female (%)

Diabetes (%)

Current Smoker (%)

CrCl < 60

Baseline Diagnosis

STEMI

NSTEMI

Unstable Angina

Stable Angina

Other

62.3 ± 11.4

16.0%

85.6 ± 17.8

25.7%

25.1%

32.3%

17.0%

20.7%

30.0%

29.5%

8.6%

11.2%

Sources of Bleeding

1. Access Site Only

2. Both Access and Non-Access

3. Non-Access Site Only

4. No Identified Location

Location of bleeds were determined post hoc using investigator-identified location and without knowledge of randomized therapy.

• Intracranial• Intraocular• Gastrointestinal• Genitourinary• Pleural• Pulmonary• Head and Neck• Epistaxis• Hemoptysis• Hematemasis• Gingival• Other

Sources and Incidence of TIMI Bleeding Among 17,393 PCI Patients

5.3% (n=925) of the study population experienced a TIMI (Major + Minor) bleeding event.

Access-site only bleeds occurred in

357 (39.6%) of patients.

Bleeding events not

limited to the access site occurred in

568 (60.4%) of patients.

Figure 2

Incidence and Location of Bleeding Events Excluding Access Site

Adjusted Relative Risk of 1-Year Mortality Based on TIMI Bleeding Source Compared to

No BleedingP<0.0001 for all bleeding versus none

Impact of Randomized Antithrombotic Therapy: All Bleeding Sources

RR=0.52P<0.0001

RR=0.55P<0.0001RR=0.55

P<0.0001

Relative Risk P-Value

Access 0.45 <0.0001

All Non-Access 0.62 <0.0001

Both 0.31 <0.0001

Non-Access Only 0.70 0.08

No Location 0.75 0.02

Bivalirudin better Hep + GPI better

0 0.5 1 1.5 2

Figure 3

Impact of Randomized Antithrombotic Therapy on TIMI Major + Minor

Bleeding by Source

Hep + GPI (%)

Bivalirudin (%)

Relative Risk

Intracranial 0.04 0.03 0.66

GI 0.64 0.28 0.44

GU 0.64 0.28 0.44

HEENT 0.33 0.22 0.66

Pulmonary 0.18 0.05 0.31

Other 0.30 0.15 0.49

No Location 1.87 1.40 0.75

All Non-Access 3.66 2.27 0.62

Hep + GPI betterBivalirudin better

Impact of Randomized Therapy on TIMI Bleeding by Location Exclusive of Access Site

Conclusions

1. Two-thirds of PCI patients with a TIMI bleed unrelated to the access site.

2. Bleeding, irrespective of the source, significantly associated with increased mortality at 1 year.

3. Non-access-related bleeding associated with double the risk of mortality compared to access bleeding.  

4. The use of bivalirudin during a PCI associated with ~40% reduction in non-access site bleeding compared with heparin + a GPIIb/IIIa antagonist.

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Risk Factors For Bleeding in ACS Patients

Patient related Procedural related Treatment related

Female genderOlderHypertensionObesityLow weightRenal failureLow platelet count. pre-existing aneamiaMedical history (GI disease)

Puncture site (femoral vs radial)Level of puncture (femoral)Larger arterial sheathProlonged sheath timeIABP placementConcomitant venous sheathNeed for repeat intervention

Over anticoagulationType of anticoagulation (antiXa. direct thrombin inhibtor or LMWH and UFH)GP IIb/IIIa inhibitorsThrombolytic

Reducing Bleeding Risk: Preventive Actions

Patient level Procedural level Treatment level

Patient information (coughing. heavy lifting to be avoided after femoral puncture)Nurse training for early recognition of retroperitoneal hemorrhage

Perfect puncture siteAngiographic control before closure device useAlternative: RADIAL AccessDifferent access sites for staged proceduresDecrease size of arterial sheath

ACT during procedures for anticoagulation monitorringDiscontinuation of antithrombin after uncomplicated PCINew Antithrombotic Agents (Bivalirudin. Fondaparinux)

Identification of Risk Factors For Bleedingin ACS Patients and Preventive actions

Hamon M. et al. EuroIntervention 2007

Identification

Prevention

24

PCI in ACS: Choice of Access Site

1. Radial Access Feasible?

2. Consider Bleeding risk?

Radial AccessConsider bleeding risk

Femoral AccessAdjunctive therapy needed?

YES NO

3. Consider Ischemic Risk?

LOW

HIGH LOW

HIGH

Default radialoperators

Am J Cardiol 2009 Hamon et al.

BivalirudinBivalirudin or GPI