SAFE-STEMI for Seniors NIH Application

Sunil V. Rao MD

SAFE-STEMI for Seniors

n Why radial vs. femoral?

n Why seniors?

Bleeding in Stable angina, NSTEMI, & STEMI

NSTEMI STEMI

Rao SV, et. al., JACC 2010

Stable Angina

Stone, TCT 2010

Harmonizing Outcomes with Revascularization and Stents in AMI

3602 pts with STEMI with symptom onset ≤12 hours

Emergent angiography, followed by triage to…

Primary PCI CABG – Medical Rx –

UFH + GP IIb/IIIa inhibitor

(abciximab or eptifibatide)

Bivalirudin monotherapy

(± provisional GP IIb/IIIa)

Aspirin, thienopyridine R

1:1

3006 pts eligible for stent randomization R

3:1

Bare metal EXPRESS stent Paclitaxel-eluting TAXUS stent

Clinical FU at 30 days, 6 months, 1 year, and then

yearly through 5 years; angio FU at 13 months

Three-Year All-Cause Mortality

P=0.03

3-yr HR [95%CI]=

0.75 [0.58, 0.97]

5.9%

7.7% A

ll-C

au

se

Mo

rta

lity (

%)

0

1

2

3

4

5

6

9

10

1611 1568

1660 1689 1670

1800 Bivalirudin alone

0 12 15 18 21 24 27 30 33 36

1098 1802 1643

Months

3 6 9

Number at risk

Heparin+GPIIb/IIIa 1633 1593

1574 1525 1043

0.71 [0.51, 0.98]

P=0.04

1-yr HR [95%CI]=

Bivalirudin alone (n=1800)

Heparin + GPIIb/IIIa (n=1802)

7

8

4.8%

3.4%

Stone, TCT 2010

R I V A L

STEMI Subgroup

STEMI NSTEMI

Mehta S, JACC 2012

All Rights Reserved, Duke Medicine 2008

Outcomes associated with transradial primary

PCI in the US

Baklanov D, et. al. JACC 2013

Higher with radial Lower with radial

RIFLE STEACS - flow chart

Design

• DESIGN:

Prospective, randomized (1:1),

parallel group, multi-center trial.

• INCLUSION CRITERIA:

all ST Elevation Acute Coronary

Syndrome (STEACS) 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

Clinical follow-up at

1 month in 100%

Femoral arm

(N=501)

Radial arm

(N=500)

Femoral arm

(N=534)

Radial arm

(N=467)

Clinical follow-up at

1 month in 100%

Intention-to-treat analysis

access shift

6.1% (61)

Romagnoli E, et. al. JACC 2012

NACE MACCE Bleeding (BARC ≥2)

overall femoral arm radial arm

p = 0.003

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

• Major Adverse Cardiac and Cerebrovascular event (MACCE) = composite of

cardiac death, myocardial infarction, target lesion revascularization, stroke

• Bleeding Academic Research Consortium (BARC) = bleeding definition adopted

30-day NACE rate

RIFLE STEACS – results

p = 0.029 p = 0.026 17.3

21.0

13.6

9.3

11.4

7.2

10.0

12.2

7.8

Romagnoli E, et. al. JACC 2012

Cardiac death Myocardial

Infarction

Target Lesion

Revascularization

Cerebrovascular

Accident

overall femoral arm radial arm

p = 0.020

30-day MACCE rate

RIFLE STEACS – results

p = 1.000 p = 0.604 p = 0.725

7.2

9.2

5.2

1.3 1.4 1.2 1.5 1.8 1.2

0.7 0.6 0.8

Romagnoli E, et. al. JACC 2012

The right patient population

n 30-day and 1-year MACE and mortality rates from STEMI are low

n A high-risk patient population is needed

l Older patients are at high risk for bleeding, mortality, and MACE

n Radial expertise in these groups is needed

Event rates: CathPCI linked with Medicare

n STEMI mortality, Age > 75 years

l 30-day: 15%

l 1-year: 23.9%

l 2-years: 29.4%

l 3-years: 34.9%

n In-hospital Bleeding rates, age > 65 years

l 3.1% (48.6% access site bleeding)

n ACTION Registry

l In-hospital major bleeding, ACS pts age ≥ 75

years 18%

Preliminary trial design

n Inclusion criteria l Age ≥ 75 years with STEMI undergoing primary PCI

l Able to give informed consent

n Exclusion criteria l Unable or unwilling to give informed consent

l Participation in another clinical trial

l Previous participation in SAFE Primary PCI

l Absent bilateral radial or femoral pulses

l Active dialysis graft in the arm to be used for radial access in case of assignment to radial approach

Preliminary trial design

n Potential Primary endpoints

l 30-day all-cause mortality

l 1-year mortality

l 1-year NACE

n NCRI infrastructure

Power calculation: 1 year NACE

n Assume 1 year event rate 15%

n Assume 4% absolute reduction

l Driven by bleeding reduction (RIFLE STEACS)

n At alpha 0.05, sample size of 1200 patients per arm

gives 80% power

n Total sample size 2500 patients

Radial trends: CathPCI

Feldman D, et. al. Circulation 2013