Dr Alex Chase

Bleeding Matters and How to Avoid It

the radial approach

RadIal Vs. femorAL access for coronary intervention in patients with acute coronary syndromes study

2006-2010

hypothesis generating

unknowns

facts

anecdotes

Bleeding is Bad

Fact 1

Fact 2Radial reduces bleeding and transfusion

•PRCTrials: SYNERGY 9,404 pts Cantor et al CCI 2007;69:73

•Meta-analyses: 1,371 pts Agostoni et al. JACC 2004;44 349

Jolly et al Canadian CC 2008

•real life registries: 593,094 pts Rao et al JACCintv 2008 1

32,822 pts Chase et al Heart 2008

The evidence is conclusive

50-70%6mm 2mm

hypothesisgenerating

unknowns

facts

So…..If bleeding is bad& 50-70% access site related…

and radial access reducesbleeding........

Does radial access reduce 30 & 1 year mortality?

39,386 PCI

procedures

Jan 1999 to

Dec 2005

in 32822

patients

311 CABG

in 10 days

7,972 radial

access

(20.6%)

30,900

femoral

access

(79.4%)

transfusion

859

(2.8%)

no

transfusion

30,041

(97.2%)

43 brachial

access

37 not

entered

transfusion

108

(1.4%)

no

transfusion

7,864

(98.6%)

1 year

mortality

1,018

(3.4%)

1 year

mortality

195

(22.7%)

1 year

mortality

198

(2.5%)

1 year

mortality

26

(24.1%)

123 repeat

procedures

same day

30 day

mortality

9

(8.3%)

30 day

mortality

69

(0.9%)

30 day

mortality

113

(13.2%)

30 day

mortality

407

(1.4%)

38,872

procedures

for analysis

M.O.R.T.A.L STUDY(Mortality benefit Of Reduced Transfusion

after PCI via the Arm or Leg)

Chase et al Heart 2008

MORTAL: log regression (n=39,386)

• age, sex, BMI, stroke, stable angina, emergency PCI, prior MI, PCI & CABG, diabetes, co-morbidities & creatinine

• reduction in transfusion radial v femoral

OR 0.56 95% CI 0.45-0.69, p<0.0001

• increase in 1 year mortality if transfused

OR 3.74 95% CI 3.12-4.47, p<0.0001

OR 0.83 95% CI 0.71-0.98, p<0.001

• reduction in 1 year mortality radial v femoral

Chase A, Hilton JD et al, Heart 2008

Oasis 5M

AC

E&

BL

EE

DIN

G

End point Odds ratio (95% CI)

Major bleeding 0.27 (0.16–0.45)

Death, stroke, or MI 0.71 (0.49–1.01)

Death 0.74 (0.42–1.30)

MI 0.76 (0.09–1.75)

Access-site crossover 3.82 (2.83–5.15)

PCI failure 1.31 (0.87–1.96)

Jolly S. Canadian Cardiovascular Congress. October 25-29, 2008; Toronto, ON.

21 study meta-analysis, >5600 ptsradial vs femoral

70%

trend

RIVIERA Study

• 7962 patients, 144 hospitals, 23 countries, 1 year

• prospective study consecutive patients

• 92% elective, 8% primary PCI (not NSTEMI)

• 10.6% via radial, 3.4% any bleeding

Montalescot et al 2007

Registry on IntraVenous anticoagulation In the Elective and

primary Real world of Angioplasty

RIVIERA Studyindependent predictors of bleeding

Montalescot et al 2007

bleeding: female, graft PCI, IIbIIIa, UFH & LMWH

only radial access reduced bleeding

(OR 0.52 CI 0.31-0.89)

RIVIERA Studyindependent predictors of death & MI

Montalescot et al 2007

•radial, clopidogrel pre-Rx & LMWH reduction in

death or MI

PREVAILProspective REgistry of Vascular Access

in Interventions in Lazio region

Heart 2008

•9 hospitals, 30 days, 1,052 consecutive vascular procedures (40% PCI)•509 radial vs 543 femoral. After Adjustment:

primary:In-hospitalmajor & minor bleedsstrokeentry complicationssecondary:In-hospitaldeath/MI

Am J Cardiol 2009;103:796–800

• specifically designed to prospectively assess impact access site

• multi- centre

• 1,170 consecutive patients after ExCr/FU

• end points: death,MI & bleeding in-hospital & 1 year

• 2003 to 2006

• bleeding diathesis

• recent bleed

• anaemia

• co-morbidity<1 year survival

• arterial disease precluding vascular access

positives exclusion criteria

PRESTO-ACS Vascular Substudy

In Hospital Outcomes

radial femoral p

bleeding 0.7% 2.4% 0.05

death&MI 2.6% 2.9% 0.79

Net Outcome 3.3% 4.6% 0.30

1 Year Outcomes

radial femoral p

bleeding 0.7% 2.7% 0.03

death&MI 4.9% 8.3% 0.05

Net Outcome 5.5% 9.9% 0.02

Am J Cardiol 2009;103:796–800

GpIIbIIIa Use 52% 34% 0.0001

hypothesis generating

unknowns

facts

anecdotes

ObservationalRetrospective

Statistics/voodoo

UnknownsWhat are possible explanations?

No causalityBleeding is a marker of high risk and poor outcomeOutcome is NOT because of the bleedPoor ‘pedigree’ or protoplasmRadial vs femoral result from chance, confounding (poor risk adjustment)

Femoral bleeds kill patientsBleed to deathBleeding causes ischaemic events

Our management of bleeding causes ischaemic events

Antiplatelet cessationTransfusion with old blood

Yes bleeding can cause death/ischaemic events but it’s GI or intracranial, not access bleeds –these are just a nuisance

Our management of ischaemia differs because of bleeding riskMore adjunct IIbIIIa in radials

hypothesis generating

unknowns

facts

anecdotes

ObservationalRetrospective

Statistics/voodoo

What Is The Evidence Linking Access Bleeds to Adverse Cardiac

Events?

Access site haematoma requiring transfusion predicts mortality

Data from the National Heart, Lung, and Blood Institute Dynamic

Registry

N=6,656

Overall 120 (1.8%) patients had access site

haematoma requiring transfusion

Over 50% of the PCIs were elective

Yatskar et al. CCI 2007;69: 961

Retrospective Analysis Of the Bivalirudin Trials: Type Of

Bleeding

• TIMI major/minor 30-day bleeding dataset from the REPLACE-2, ACUITY and HORIZONS-AMI trials in 17,393 femoral PCI patients.

• TIMI major/minor bleeding 5.3% (1.6%/3.7%)

• 38.2% of which were only-access site bleeds.

• After multivariable adjustment, TIMI bleeding increased risk of 1-year mortality (HR 3.17 (95%CI 2.51–4.00), p<0.0001).

• mortality risk non-access site TIMI bleedHR 3.94 (95%CI 3.07–5.15), p<0.0001

• adjusted mortality risk access site-only TIMI bleed HR 1.82 (95%CI 1.17–2.83), p=0.008

• adjusted mortality risk non-access site bleed was 2 fold that of an access site bleedHR 2.27 (95%CI 1.42-3.64), p=0.0007

Verheugt, Steg et alPersonal communication

RE

PL

AC

E2

TIMI minor

TIMI major

NonTIMI

AC

UIT

YH

OR

IZO

NS

Bival Trials

Mehran et alESC 2009

17,002 pts

M.O.R.T.A.L STUDY Chart Review(Mortality benefit Of Reduced Transfusion after PCI via the Arm or Leg)

• 38,952 patients 952 transfusions (2.5%)

• Impact of source of bleeding

121831

% %

SD Robinson 2010 CCS

alive dead

†: p<0.05

M.O.R.T.A.L Study Chart Review

•higher transfusion volumes predicted increased risk of death (OR 1.25 [1.16-1.34], p=0.008)

•patients dying within 30 days more often received blood stored for at least 28 days (65.3 vs 52.9%, p=0.02)

• After adjustment for baseline risk, RBC storageage >28 days (odds ratio 2.46 [95% CI 1.44 –4.21], p=0.001)

•Transfusion of other blood products than RBCs After adjustment for baseline risk, transfusion of platelets (OR 2.27 [95% C.I. 1.17-4.44]) and plasma/cryoprecipitate (OR 4.95 [2.67-9.19]) predicted an increased risk of death at 30 days

SD Robinson 2010 CCS

Undoes your anticoag

Robinson 2010 CCS

M.O.R.T.A.L Study Chart Review

transfused alive

non transfuseddead 30 days

transfused dead 30 days

PREVAIL- Internet Only AppendicesProspective REgistry of Vascular Access in Interventions in

Lazio region

Heart 2008

•9 hospitals, 30 days, 1,052 consecutive pts•509 radial vs 543 femoral. After Adjustment:

primary:In-hospitalmajor & minor bleedsstrokeentry complicationssecondary:In-hospitaldeath/MI

bleeds- femoral access site

• 1 death directly from femoral access bleed

• 2 other major bleeds requiring transfusion

• 4 pseudoaneurysms, 2 x AV fistula

• 1 x stroke

• 15 minor bleeds 1-10cm haematoma without transfusion

bleeds radial access

• 1 spontaneous RP haematoma (prosthetic valve) – death

• no major access bleeds

• zero transfusions

• 6 minor bleeds 0-5cm haematoma without transfusion

9 hospitals, 30 days, 1,052 consecutive pts509 radial vs 543 femoral

PREVAILBreakdown - Complex Composite

End Point Per Treatment

Heart 2008

Massive haematoma

NSTEMIdeath

PREVAILIschemic Endpoint- Adjunct

Therapy Hypothesis

stable ACS

ischemic endpoint

(death & MI)

IIbIIIa use radial 15% vs femoral 8%, p=0.002

Heart 2008

Vascular Closure Devices Birmingham 2004-2005

1214 PCI (1077 fem:137 radial)

15 vascular complications 1.2%

transfusion 0.64% femoral PCI n=7, 1077 Routledge, Ludman et al

? impactspeculative calculation

• difference transfusion rate 2.8 -1.4%=1.4%

• if save 3 patients transfusions / 200 PCI

• need to prevent 7.4 transfusions to save 1 life @ 1 year

• ? 1’avoided death’ / 500 cases

• ? diagnostic angiograms1.5 x106

74,000

Chase et al Heart 2008

Bleeding Matters and How to Avoid It

the radial approach• Increased patient comfort

• Early ambulation

• Reduced hospital stay

• Reduced vascular complications

• Reduced Nursing requirements

• Reduced cost

Questions

hypothesis generating

unknowns

facts