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
21 st Cardiology Update February 11, 2015 Is FFR essential to guide PCI? William Wijns Aalst, B Percutaneous Interventions
Is FFR essential to guide PCI? 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
Revascularisation vs Best Medical Therapy 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
DEFER Study Results at 5 years FFR > 0.75 FFR < 0.75 No PCI PCI PCI DEFER PERFORM REFERENCE 20 % 10 3.3 % 0 Death/MI after 5 years NS 7.9 % P<0.003 15.7 % When FFR > 0.75 Death and MI rate is < 1% per year Pijls et al, JACC 2007;49:2105-1. www.escardio.org/guidelines Joint 2010 ESC - EACTS Guidelines on Myocardial Revascularisation
Revascularisation vs Best Medical Therapy No benefit of PCI in the absence of ischemia Evidence for benefit of PCI In the presence 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 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
FAME 2 Flow Chart Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220 Randomized Trial FFR in all target lesions Registry At least 1 stenosis with FFR 0.80 (n=888) When all FFR > 0.80 (n=332) Randomization 1:1 PCI + MT 73% MT 27% MT 50% randomly assigned to FU Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years
Cumulative incidence (%) FAME 2 Primary Outcomes 20 PCI+MT vs. MT: HR 0.39 (95% CI 0.26-0.57) P<0.001 PCI+MT vs. Registry: HR 0.90 (95% CI 0.49-1.64) P=0.72 MT vs. Registry: HR 2.34 (95% CI 1.35-4.05) P=0.002 15 PCI+MT MT alone Registry 10 5 0 No. at risk MT PCI+MT Registry 0 2 4 6 8 10 12 14 16 18 20 22 24 Months after randomization 441 417 398 389 379 369 362 360 359 355 353 351 297 447 434 429 426 425 420 416 414 410 408 405 403 344 166 164 162 160 157 157 156 153 151 150 150 150 122
Cumulative Urgent Revascularization Events per 100 patients-years Urgent revascularizations according to different triggers for the revascularization 24 PCI + MT MT alone 20 16 12 8 4 0 0 4 8 12 16 20 24 Months after Revascularisation 0 4 8 12 16 20 24 Months after Revascularisation Urgent revascularization was triggered in >80% by an MI, by dynamic ST changes, or by resting angina
FAME 2 - Landmark Analysis www.cardio-aalst.be
FAME 2 Symptoms Cumulative incidence (%) Baseline PCI+MT MT alone Registry 30 Days PCI+MT 45/441 0.36 (0.26-0.49) <0.001 0.66 (0.42-1.04) 0.08 MT alone Registry 6 Months PCI+MT MT alone Registry 40 35 30 25 20 123/431 25/162 PCI+MT vs. MT: HR 0.16 (95% CI 0.11-0.22) P<0.001 PCI+MT vs. Registry: HR 0.66 (95% CI 0.38-1.14) P=0.13 MT vs. Registry: HR 4.26 (95% CI 2.66-6.81) P<0.001 33/440 80/434 26/163 1.00 (reference) Total Revascularisations 0.41 (0.28-0.60) 1.00 (reference) <0.001 1.85 (1.25-2.73) 1.00 (reference) 0.47 (0.29-0.76) 1.16 (0.77-1.73) 1.00 (reference) 0.001 0.002 0.48 12 Months PCI+MT MT alone Registry 24 Months PCI+MT MT alone Registry 15 10 5 0 No. at risk MT PCI+MT Registry 26/437 65/429 25/159 0 2 4 6 8 10 12 14 16 18 20 22 24 Months after randomization 25/425 441 389 360 337 315 302 290 277 272 268 260 254 218 447 440 434 429 427 422 417 410 407 406 402 399 343 166 165 162 160 157 156 153 149 144 142 141 141 116 51/424 23/157 0.39 (0.25-0.61) 1.00 (reference) 0.49 (0.31-0.77) 1.00 (reference) <0.001 0.002 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) <0.001 0.86 0.001 0.40 0 20 40 Patients with CCS II to IV (%)
Is FFR essential to guide PCI? 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)
Only Angiography Angiography + FFR 15 10 5 Cumulative incidence (%) 20 PCI+MT MT alone 0 2 4 6 8 10 12 14 16 18 20 22 24 COURAGE NEJM 2007 FAME 2 NEJM 2014
Is FFR essential to guide PCI? What if the benefit of revascularisation by PCI was confounded by failure to restrict stent implantation to ischemic stenoses (FFR +)
FAME 1 Guidance Randomised Trial Event-free rates at 2 years MACE Death or MI* Death CABG or PCI 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 II = 30% of cases Stenosis but no ischemia Wrong target for PCI No benefit, potential harm Waste of resources IV IV = 20% of cases Deferral is inappropriate Missed opportunity Angiographic guidance to revascularization results in inappropriate intervention in ~50% of cases
21 st Cardiology Update February 11, 2015 Is FFR essential to guide PCI? Evaluation of ischemia is essential to guide revascularisation by PCI (and CABG)
ISCHEMIA Trial