Radial Approach: Clinical Trials...

Radial Approach: Clinical Trials and

Α-Δ. ΜΑΥΡΟΓΙΑΝΝΗΚΑΡΔΙΟΛΟΓΟΣ

AIMOΔΥΝΑΜΙΚΟ ΕΡΓΑΣΤΗΡΙΟΓ.Ν.Θ. «Γ.ΠΑΠΑΝΙΚΟΛΑΟΥ»

ΘΕΣΣΑΛΟΝΙΚΗTuesday, March 10, 15

Disclosure Statement of Financial Interest

None whatsoever…

Tuesday, March 10, 15

Why are we talking about access?

Michelangelo di Lodovico Buonarroti Simoni (1475 – 1564): The Creation of Adam, Sistine Chapel ceiling circa 1511–1512


Why are we talking about access?

Michelangelo di Lodovico Buonarroti Simoni (1475 – 1564): The Creation of Adam, Sistine Chapel ceiling circa 1511–1512

…same painter, same painting, different perspective…


Bleeding…


Day 0 – 2 after MI 12.6 (7.8-20.4)12.6 (7.8-20.4) 29 (37.6) <0.0001<0.0001Day 3 – 7 after MI 5.3 (2.7-10.4)5.3 (2.7-10.4) 11 (14.3) <0.0001<0.0001

Day 8 – 35 after MI 1.6 (0.8-3.1)1.6 (0.8-3.1) 12 (15.6) 0.180.18Day > 35 after MI 1.2 (0.8-1.9)1.2 (0.8-1.9) 25 (32.5) 0.340.34

Day 0 – 2 after Major Bleed 3.0 (1.6-5.6)3.0 (1.6-5.6) 12 (12.9) 0.00090.0009Day 3 – 7 after Major Bleed 4.0 (2.1-7.5)4.0 (2.1-7.5) 15 (16.1) <0.0001<0.0001

Day 8 – 35 after Major Bleed 4.5 (2.8-7.4)4.5 (2.8-7.4) 25 (26.9) <0.0001<0.0001Day > 35 after Major Bleed 2.2 (1.5-3.2)2.2 (1.5-3.2) 41 (44.1) <0.0001<0.0001

P-value

Lessons Learnt from Acuity:Non CABG Major Bleeding and MI in the First 30 Days on the Risk of Death Over 1 Year

Deaths (n/%)HR ± 95% CI

0.5 1 2 4 8 16

HR (CI)

Mehran R. et al.Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute

coronary syndromes: a risk model from the ACUITY trial. Eur Heart J.2009 Jun;30(12):1457-66


Risk for 1 year mortality N=17393 pts from REPLACE-2, ACUITY, HORIZONS AMI

Verheugt FW. et al.Incidence, prognostic impact, and influence of antithrombotic therapy on access and nonaccess site bleeding inpercutaneous coronary intervention.

JACC Cardiovasc Interv. 2011 Feb;4(2):191-7Tuesday, March 10, 15

Doyle BJ. et al.Major femoral bleeding complications after percutaneous coronary intervention: incidence, predictors, and impact on long-term survival among 17,901

patients treated at the Mayo Clinic from 1994 to 2005. JACC Cardiovasc Interv. 2008 Apr;1(2):202-9


Bleeding: NCDR CathPCI Rates

70%

30%

acces sitenon access site

70%

30%

non access siteaccess site

55%

45%

non access site access site

Stable Angina NSTEMI STEMI Overall Rate 2.1% Overall Rate 4.8% Overall Rate 12.7%

Rao SV. et al.The transradial approach to percutaneous coronary intervention: historical perspective, current concepts, and future directions.

J Am Coll Cardiol.2010 May 18;55(20):2187-95Tuesday, March 10, 15

RADIAL VERSUS FEMORAL RANDOMIZED INVESTIGATION

IN ST ELEVATION ACUTE CORONARY SYNDROME

Principal investigators:Enrico Romagnoli, MD PhDGiuseppe Biondi-Zoccai, MD

Giuseppe Sangiorgi, MD

F R


RIFLE STEACS - flow chartDesign

• DESIGN: Prospective, randomized (1:1),

parallel group, multi-center trial.

• INCLUSION CRITERIA: all ST Elevation Myocardial infarction

(STEMI) eligible for primary percutaneous coronary intervention.

• ESCLUSION CRITERIA: contraindication to any of both

percutaneous arterial access.

international normalized ratio (INR) > 2.0.

1001 patients enrolled between January 2009 and July 2011 in 4 clinical sites in Italy











Femoral arm (N=501) Radial arm(N=500)













4.7% 1.4%











Clinical follow-up at 1 month in 100%



Clinical follow-up at 1 month in 100%

Intention-to-treat analysis

4.7% 1.4%


NACE MACCE Bleedings

femoral arm radial armp = 0.003

• Net Adverse Clinical Event (NACE) = MACCE + bleeding

30-day NACE rate

RIFLE STEACS results

p = 0.029 p = 0.026

21.0%

11.4%

7.2%

12.2%

7.8%

13.6%

Romagnoli E. et al.Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral

Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol.2012 Dec 18;60(24):2481-9


Cardiac death Myocardial InfarctionTarget Lesion RevascularizationCerebrovascular Accident

femoral arm radial armp = 0.020

30-day MACCE rate

RIFLE STEACS – results

p = 1.000 p = 0.604 p = 0.725

9.2%

5.2%

1.4% 1.2% 1.8% 1.2% 0.6% 0.8%




30-day bleeding rate


p = 1.000

12.2%

6.8%

2.6%5.4% 5.2%

p = 0.026

Bleedings Access site related Non access site related

femoral arm radial arm

7.8%

p = 0.002




30-day bleeding rate


p = 1.000

12.2%

6.8%

2.6%5.4% 5.2%

p = 0.026

Bleedings Access site related Non access site related


7.8%

47%

p = 0.002




A RANDOMIZED COMPARISON OF RADIAL VS. FEMORAL ACCESS FOR CORONARY INTERVENTION IN ACS

SS Jolly, S Yusuf, J Cairns, K Niemela, D Xavier, P Widimsky, A Budaj, M Niemela, V Valentin, BS Lewis,

A Avezum, PG Steg, SV Rao, P Gao, R Afzal, CD Joyner, S Chrolavicius, SR Mehta on behalf of the

RIVAL investigators

Jolly SS. et al.Design and rationale of the radial versus femoral access for coronary intervention (RIVAL) trial: a randomized comparison of radial versus femoral access

for coronary angiography or intervention in patients with acute coronary syndromes. Am Heart J. 2011 Feb;161(2):254-260


NSTE-ACS and STEMI(n=7021)

RIVAL Study Design

Key Inclusion: • Intact dual circulation of hand required• Interventionalist experienced with both (minimum 50 radial

procedures in last year)



Radial Access(n=3507)

Femoral Access(n=3514)

Randomization

RIVAL Study Design







Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days

Randomization

RIVAL Study Design



Blinded Adjudication of Outcomes





Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days

Randomization

RIVAL Study Design



Blinded Adjudication of Outcomes

Diagnosis at presentationDiagnosis at presentationDiagnosis at presentation UA (%) 44.3 45.7

NSTEMI (%) 28.5 25.8

STEMI (%) 27.2 28.5


RIVAL:Primary and Secondary Outcomes

Radial(n=3507)

%

Femoral (n=3514)

%HR 95% CI P

Primary OutcomePrimary OutcomePrimary OutcomePrimary OutcomePrimary OutcomePrimary OutcomeDeath, MI, Stroke, Non-CABG Major Bleed

3.7 4.0 0.92 0.72-1.17 0.50

Secondary OutcomesSecondary OutcomesSecondary OutcomesSecondary OutcomesSecondary OutcomesSecondary OutcomesDeath, MI, Stroke 3.2 3.2 0.98 0.77-1.28 0.90Non-CABG Major Bleeding 0.7 0.9 0.73 0.43-1.23 0.23

Jolly SS. et al.Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group,

multicentre trial. Lancet.2011 Apr 23;377(9775):1409-20


RIVAL: Other Outcomes

Radial(n=3507)

%

Femoral (n=3514)

%HR 95% CI P

Major Vascular Access Site Complications

1.4 3.7 0.37 0.27-0.52 <0.0001

Other Definitions of Major BleedingOther Definitions of Major BleedingOther Definitions of Major BleedingOther Definitions of Major BleedingOther Definitions of Major BleedingOther Definitions of Major BleedingTIMI Non-CABG Major Bleeding

0.5 0.5 1.00 0.53-1.89 1.00

ACUITY Non-CABG Major Bleeding*

1.9 4.5 0.43 0.32-0.57 <0.0001

Jolly SS. et al.Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group,

multicentre trial. Lancet.2011 Apr 23;377(9775):1409-20


NSTE/ACSSTEMI

NSTE/ACSSTEMI

NSTE/ACSSTEMI

NSTE/ACSSTEMI

NSTE/ACSSTEMI

50631958

50631958

50631958

50631958

50631958

3.55.2

2.74.6

0.83.2

1.00.9

3.83.5

3.83.1

3.42.7

1.21.3

0.60.8

1.41.3

0.25 1.00 4.00Radial better Femoral better

Hazard Ratio(95% CI)

0.025

0.011

0.001

0.56

0.89

Interactionp-value

2N Radial Femoral% %

Primary Outcome

Death, MI or stroke

Death

Non CABG Major Bleed

Major Vascular Complications

Outcomes stratified by STEMI vs. NSTEACS


0.25 1.00 4.00 16.00Radial better Femoral better

High MediumLow

High MediumLow

High MediumLow

HighMediumLow

HighMediumLow

0.021

0.013

0.538

0.019

0.003

Interactionp-valueHR (95% CI)

Primary Outcome

Death, MI or stroke

Non CABG Major Bleed

Major Vascular Complications

Access site Cross-over

Results stratified by High*, Medium* and Low* Volume Radial Centres

No significant interaction by Femoral PCI center volume

Tertiles of Radial PCI Centre Volume/yr

*High (>146 radial PCI/year/ median operator at centre), Medium (61-146), Low (≤60)


MACE Death MI Stroke


p = 0.7

30-day MACE

STEMI RADIAL - results

p = 0.64

p = 0.72

p = 1.0

4.2%3.5%

3.1%2.3%

0.8%1.2%

0.3% 0.3%

Bernat I. et al.ST-segment elevation myocardial infarction treated by radial or femoral approach in a multicenter randomizedclinical trial: the STEMI-RADIAL trial.

J Am Coll Cardiol. 2014 Mar 18;63(10):964-72


NACE Bleeding MACE

femoral radialp = 0.0028

30-day NACE

STEMI RADIAL - results

p = 0.7

p = 0.0001

11.0%

7.2%

1.4%

4.2% 3.5%4.6% 80%

58%


J Am Coll Cardiol. 2014 Mar 18;63(10):964-72


Gastro- intestinalHb drop ≥4g/dL w/o overtHb drop ≥3g/dL with overtHematoma ≥15cm Transfusion Vascular complication

0.3%0%0.6%0.9%

0.3%0.3% 0.8%0.8%

5.3%

2.8%

0.3%1.1%

femoral radial

STEMI RADIAL - results30-day bleeding and access site compl.


J Am Coll Cardiol. 2014 Mar 18;63(10):964-72Tuesday, March 10, 15


0.3%0%0.6%0.9%

0.3%0.3% 0.8%0.8%

5.3%

2.8%

0.3%1.1%

femoral radial


Primary EP

1.4%

7.2% p=0.0001




0.3%0%0.6%0.9%

0.3%0.3% 0.8%0.8%

5.3%

2.8%

0.3%1.1%

femoral radial


Primary EP

1.4%

7.2% p=0.0001

80%



Femoral vs Radial:Rates of Bleeding and Vascular Complications in Key Subgroups

Rao SV. et al.Trends in the prevalence and outcomes of radial and femoral approaches to percutaneous coronary intervention: a report from the National

Cardiovascular Data Registry. JACC Cardiovasc Interv. 2008 Aug;1(4):379-86


Femoral vs Radial: Outcomes “(cont.)”

Feldman DN. et al.Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national

cardiovascular data registry (2007-2012). Circulation. 2013 Jun 11;127(23):2295-306


Vascular Complications Associated with FA and RARetrospective review of 5,234 cath and PCIVascular complications by BMI: lower rate of vascular complications using TR vs. TF approach for obese and non obese patients

Cox N. et al.Comparison of the risk of vascular complications associated with femoral and radial access coronary catheterization procedures in obese versus

nonobese patients. Am J Cardiol. 2004 Nov 1;94(9):1174-7


Access Site Practice and Procedural Outcomes in Relation toClinical Presentation in Patients Undergoing PCI

Multivariate Analysis:Multivariate Analysis:Multivariate Analysis:Radial vs Femoral PCI OR 95% CIRadial vs Femoral PCI OR 95% CIRadial vs Femoral PCI OR 95% CI

30-Day MortalityStable 0.77 0.61-0.97NSTE-ACS 0.76 0.67-0.85STEMI 0.72 0.65-0.79

BleedingStable 0.24 0.16-0.36NSTE-ACS 0.35 0.27-0.44STEMI 0.47 0.39-0.58

Ratib K et al.Access site practice and procedural outcomes in relation to clinical presentation in 439,947 patients undergoing percutaneous coronary intervention in the

United kingdom. JACC Cardiovasc Interv. 2015 Jan;8(1 Pt A):20-9


Arterial Access Site Selection on Outcomes in PPCIAre the Results of Randomized Trials Achievable in Clinical

Mamas MA. et al.Baseline bleeding risk and arterial access site practice in relation to procedural outcomes after percutaneous coronary intervention.

J Am Coll Cardiol. 2014 Oct 14;64(15):1554-64


Baseline Bleeding Risk and Benefit of Transradial PCI: Making Lemonade out of Lemons




Arterial Access Site Selection on Outcomes in PPCIAre the Results of Randomized Trials Achievable in Clinical Practice?




TRI vs TFI: Death

Piccolo R. et al.Transradial versus transfemoral approach in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

A meta-analysis and trial sequential analysis of randomized controlled trials. PLoS One. 2014 May 12;9(5):e96127


TRI vs TFI: Major Bleeding




TRI vs TFI: Vascular Complications




TRI Complication Decrease:One Size Fits All




“Paradox”: a Self-Contradictory and False Proposition

Maurits Cornelis Escher (1898 – 1972) : Impossible Realities/ Drawing Hands 1948, Relativity 1953


The Radial Paradox: Underutilization in Key Subgroups

Rao SV. et al.Trends in the prevalence and outcomes of radial and femoral approaches to percutaneous coronary intervention: a report from the National

Cardiovascular Data Registry. JACC Cardiovasc Interv. 2008 Aug;1(4):379-86


Radial Access for All: Practice Makes Better

! Superficial position: easy to find! Improved techniques! Improved materials! Early days: access failure 7.3%! Nowadays: need for conversion < 1.5%! Mean difference in procedural time ~ 1.76´ ! Learning Curve

Spaulding C. et al.Left radial approach for coronary angiography: results of a prospective study.

Cathet Cardiovasc Diagn.1996 Dec;39(4):365-70


How, Who, When: Guidelines and Recommendations

Authors/Task Force members2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and

the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Eur Heart J. 2014 Oct 1;35(37):2541-619

Hamon M. et al.Consensus document on the radial approach in percutaneous cardiovascular interventions: position paper by the European Association of Percutaneous Cardiovascular

Interventions and Workin Groups on Acute Cardiac Care** and Thrombosis of the European Society of Cardiology. EuroIntervention. 2013 Mar;8(11):1242-51


! Vascular access is the first procedural interaction you have with the patient! They remember the access, not the fact that you saved their life with PCI

! There is no one approach that suits all patients ! All interventional cardiologists should be proficient

Albrecht Dürer (1471 – 1528): Study of three hands circa 1490


One has to know the Whole Picture…

Michelangelo di Lodovico Buonarroti Simoni (1475 – 1564): The Creation of Adam,Sistine Chapel ceiling circa 1511–1512


TRI vs TFI: Reduced Complications and Mortality NSTEMI Patients

AdjustedAdjustedAdjustedAdjusted

Radial vs Femoral OR/HR 95%CI P Value

Total Bleeding 0.21 0.08-0.57 .002

1 Year Mortality 0.72 0.54-0.94 .017

Iqbal MB. et al.Radial versus femoral access is associated with reduced complications and mortality in patients with non-ST-segment-elevation myocardial infarction:

an observational cohort study of 10,095 patients. Circ Cardiovasc Interv.2014 Aug;7(4):456-64

10,095 consecutive NSTEMI patients who underwent radial (n = 2,275) or femoral (n = 7,820) PCI 8 centers in London, 2005 to 2011


Radial Approach: Clinical Trials...

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