Relations of Interest

• Consulting Fees on my behalf go to the Cardiovascular Research Center Aalst

• Contracted Research between the Cardiovascular Research Center Aalst and several pharmaceutical and device companies, including StJude, HeartFlow, Opsense, Volcano

• Ownership Interest: Co-founder and Board member of Argonauts, Genae and Cardio³BioSciences (cell-based regeneration cardiovascular therapies)

• Chairman of PCR

• Co-Chairman of AfricaPCR

• Co-Chairman of EuroPCR, the annual Course of EAPCI

Is FFR essential to guide PCI?

William Wijns Aalst, B

Percutaneous Interventions

21st Cardiology Update

February 11, 2015

• Decision to perform PCI is based on global appraisal of the clinical condition, functional evaluation, procedural benefits and risks, and coronary anatomy

• When functional evaluation is not available or inconclusive, FFR can be applied on the spot, with high spatial resolution to inform decision-making

Is FFR essential to guide PCI?

No benefit of PCI

in the absence of ischemia

1998: Nuclear imaging studies

2005: Besançon randomised trial*

2007: Defer randomised trial

2012: FAME 2 registry

2013: SJ Park registry**

2013: Mayo Clinic registry ***

* Legalery, Eur Heart J 26:2623

** Eur Heart J 34:3553

*** Lim, Eur Heart J 34:1375-83

Revascularisation vs Best Medical Therapy

www.escardio.org/guidelines Joint 2010 ESC - EACTS Guidelines on Myocardial Revascularisation

DEFER Study Results at 5 years

PCI PCI No PCI

FFR > 0.75 FFR < 0.75

NS P<0.003

0

10

20

% 15.7 %

7.9 %

3.3 %

Death/MI after 5 years

When FFR > 0.75 Death and MI rate is < 1% per year

REFERENCE DEFER PERFORM

Pijls et al, JACC 2007;49:2105-1.

Evidence for benefit of PCI

In the presence of ischemia

1997: ACIP trial

2003: Nuclear imaging studies

2008: Nuclear substudy COURAGE

2009: Substudy of BARI 2 D

2012: FAME 2 randomised trial

2013: Mayo Clinic registry***

20XX: ISCHEMIA trial

No benefit of PCI

in the absence of ischemia

1998: Nuclear imaging studies

2005: Besançon randomised trial*

2007: Defer randomised trial

2012: FAME 2 registry

2013: SJ Park registry**

2013: Mayo Clinic registry ***

* Legalery, Eur Heart J 26:2623

** Eur Heart J 34:3553

*** Lim, Eur Heart J 34:1375-83

Revascularisation vs Best Medical Therapy

FAME 2 Flow Chart

Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI

N = 1220

When all FFR > 0.80 (n=332)

MT

At least 1 stenosis with FFR ≤ 0.80 (n=888)

Randomization 1:1

PCI + MT MT

Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

FFR in all target lesions

Registry

50% randomly

assigned to FU 27%

Randomized Trial

73%

FAME 2 Primary Outcomes

0

5

10

15

20

Cum

ula

tive incid

ence (

%)

166 164 162 160 157 157 156 153 151 150 150 150 122 Registry

447 434 429 426 425 420 416 414 410 408 405 403 344 PCI+MT 441 417 398 389 379 369 362 360 359 355 353 351 297 MT

No. at risk

0 2 4 6 8 10 12 14 16 18 20 22 24 Months after randomization

MT vs. Registry: HR 2.34 (95% CI 1.35-4.05) P=0.002

PCI+MT vs. Registry: HR 0.90 (95% CI 0.49-1.64) P=0.72

PCI+MT vs. MT: HR 0.39 (95% CI 0.26-0.57) P<0.001

MT alone

Registry

PCI+MT

Urgent revascularizations according to

different triggers for the revascularization

Months after Revascularisation

0 4 8 12 16 20 24 Months after Revascularisation

0 4 8 12 16 20 24

0

4

8

12

16

20

24 PCI + MT MT alone

Cu

mu

lati

ve U

rgen

t R

evas

cula

riza

tio

n

Even

ts p

er

10

0 p

atie

nts

-yea

rs

Urgent revascularization was triggered in >80% by an MI,

by dynamic ST changes, or by resting angina

ww

w.c

ard

io-a

als

t.b

e

FAME 2 - Landmark Analysis

Baseline PCI+MT

MT alone

Registry

30 Days PCI+MT

MT alone

Registry

6 Months PCI+MT

MT alone

Registry

12 Months PCI+MT

MT alone

Registry

24 Months PCI+MT

MT alone

Registry

0 20 40 Patients with CCS II to IV (%)

FAME 2 Symptoms

0

5

10

15

20

25

30

35

40

Cum

ula

tive incid

ence (

%)

166 165 162 160 157 156 153 149 144 142 141 141 116 Registry

447 440 434 429 427 422 417 410 407 406 402 399 343 PCI+MT

441 389 360 337 315 302 290 277 272 268 260 254 218 MT

No. at risk

0 2 4 6 8 10 12 14 16 18 20 22 24 Months after randomization

MT vs. Registry: HR 4.26 (95% CI 2.66-6.81) P<0.001

PCI+MT vs. Registry: HR 0.66 (95% CI 0.38-1.14) P=0.13

PCI+MT vs. MT: HR 0.16 (95% CI 0.11-0.22) P<0.001

Total Revascularisations

45/441

123/431

25/162

33/440

80/434

26/163

26/437

65/429

25/159

25/425

51/424

23/157

0.36 (0.26-0.49)

1.00 (reference)

0.41 (0.28-0.60)

1.00 (reference)

0.39 (0.25-0.61)

1.00 (reference)

0.49 (0.31-0.77)

1.00 (reference)

<0.001

<0.001

<0.001

0.002

0.66 (0.42-1.04)

1.85 (1.25-2.73)

1.00 (reference)

0.47 (0.29-0.76)

1.16 (0.77-1.73)

1.00 (reference)

0.38 (0.23-0.64)

0.96 (0.63-1.47)

1.00 (reference)

0.40 (0.23-0.69)

0.82 (0.52-1.30)

1.00 (reference)

0.08

0.001

0.002

0.48

<0.001

0.86

0.001

0.40

• In order to optimise appropriate use of revascularisation, dual targeting (by anatomy and function) is to be recommended

• Then outcomes are prognostically superior and symptomatically equivalent to those obtained with single targeting (by anatomy only)

Is FFR essential to guide PCI?

COURAGE

NEJM 2007

Only

Angiography

5

10

15

20

Cum

ula

tive

in

cid

en

ce

(%

)

0 2 4 6 8 10 12 14 16 18 20 22 24

PCI+MT

MT alone

Angiography

+ FFR

FAME 2

NEJM 2014

What if the benefit of revascularisation by PCI was confounded by …

failure to restrict stent implantation to ischemic stenoses (FFR +)

Is FFR essential to guide PCI?

FAME 1 Guidance Randomised Trial

Event-free rates at 2 years

MACE

Death CABG or PCI

Death or MI*

Pijls et al. JACC 2010:56;177

Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

N Johnson, JACC 2014: 64;1641

Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes

N Johnson, JACC 2014: 64;1641

Global Adoption of FFR remains limited

6%

Courtesy of J.Escaned

FFR to identify appropriate targets for PCI

Toth G et al, ISIS survey, Circ CV Interv 2014:7;751

FFR to identify appropriate targets for PCI

No perceived need for FFR

Toth G et al, ISIS survey, Circ CV Interv 2014:7;751

Why apply functional indices?

II

IV IV = 20% of cases Deferral is inappropriate Missed opportunity

II = 30% of cases Stenosis but no ischemia Wrong target for PCI No benefit, potential harm Waste of resources

Angiographic guidance to revascularization results in inappropriate intervention in ~50% of cases

Is FFR essential to guide PCI?

Evaluation of ischemia is essential to guide revascularisation

by PCI (and CABG)

21st Cardiology Update

February 11, 2015

ISCHEMIA Trial