Role of FFR-Guided PCI in Patients with Stable CAD William F. - PDF document

12/8/19 Role of FFR-Guided PCI in Patients with Stable CAD William F. Fearon, MD Professor of Medicine Director, Interventional Cardiology Stanford University School of Medicine 1 Conflicts of Interest n Research grants from Medtronic and Abbott Vascular n Consulting with HeartFlow and CathWorks n Research and salary support from National Institutes of Health: R61/R33 HL139929 (PI) n Interventional Cardiologist!! 2 1

12/8/19 November 2, 2017 3 Brown DL and Redberg RF. Lancet 2018;391:3-4. 4 2

12/8/19 Surgery for Blocked Arteries Is Often Unwarranted, Researchers Find Drug therapy alone may save lives as effectively as bypass or stenting procedures, a large federal study showed. November 16, 2019 5 6 3

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12/8/19 COURAGE: Aim n To determine whether the addition of PCI to optimal medical therapy, when used as an initial management strategy, further reduces the risk of death or nonfatal MI in patients with stable CAD, compared with optimal medical therapy alone. 9 COURAGE: Results 2,287 stable patients with 1, 2, or 3 vessel CAD randomized to optimal medical therapy or PCI Boden, et al. New Engl J Med 2007;356:1503-16. 10 5

12/8/19 Degree of Ischemia in COURAGE Shaw, et al. Circulation 2008;117:1283-91. 11 Importance of Myocardial Ischemia With greater degrees of ischemia, there is a survival benefit for PCI 10% Ischemic Myocardium P<0.001 Hachamovitch, et al. Circulation 2003;107:2900-06. 12 6

12/8/19 Why didn’t COURAGE show a benefit with PCI? n It did not included patients with significant myocardial ischemia n PCI was not optimal (No DES, incomplete revascularization) n PCI was not guided by Fractional Flow Reserve (FFR) 13 Fractional Flow Reserve Proximal Pressure (Pa) Distal FFR = P d / P a Pressure (Pd) during maximal flow P a P d P d / P a = 60 / 100 FFR = 0.60 14 7

12/8/19 Limitation of Angiography 1329 lesions in the FFR-guided arm of FAME ~20% ~35% Tonino, et al.J Am Coll Cardiol 2010;55:2816-21. 15 DEFER Trial 15 Year Follow-Up 181 patients with intermediate lesions and FFR≥0.75 randomized to deferral or performance of PCI Zimmermann, et al. Eur Heart J 2015;36:3182-8 16 8

12/8/19 Safety of Deferring PCI Based on FFR 5 year follow-up of 564 intermediate proximal LAD lesions deferred because FFR≥0.80 No Known CAD Moderate Prox LAD, FFR≥0.80 Adapted from: Muller, et al. JACC Cardiovasc Interv 2011;4:1175-82 17 FAME 1 Study: One Year Outcomes 1,005 patients with multivessel CAD randomized to FFR or Angio-guided PCI Angio-Guided FFR-Guided % ~30% ¯ 20 18.3 15 ~35% ¯ 13.2 ~30% ¯ ~35% ¯ 11.1 9.5 10 8.7 7.3 6.5 ~40% ¯ 5.7 5 3 1.8 0 Death MI Repeat Death/MI MACE Revasc p=0.04 p=0.02 New Engl J Med 2009;360:213-24. 18 9

12/8/19 FAME Study: Two Year Outcomes Death/MI was significantly reduced from 12.9% to 8.4% (p=0.02) Survival Free of MACE FFR-Guided Angio-Guided 730 days 4.5% Pijls, et al. J Am Coll Cardiol 2010;56:177-184 19 FAME: Economic Evaluation Bootstrap Analysis FFR-guided PCI saved >$2,000 per patient at one year compared to Angio- guided PCI Circulation 2010;122:2545-50. 20 10

12/8/19 Implications of FAME Death and MI in the COURAGE study FAME 2 Boden et al., New Engl J Med 2007;356:1503-16. 21 FAME 2: Design n Hypothesis: q Optimal medical therapy plus FFR-guided PCI with current generation drug-eluting stents improves outcomes compared to optimal medical therapy alone in patients with stable coronary artery disease. De Bruyne, et al. New Engl J Med 2012;367:991-1001 22 11

12/8/19 FAME 2 Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220 FFR in all target lesions Registry Randomized Trial When all FFR > 0.80 At least 1 stenosis (n=332) with FFR ≤ 0.80 (n=888) Randomization 1:1 PCI + MT MT MT 27% 50% randomly 73% assigned to FU Primary Endpoint: Death, MI or Urgent Revascularization at 2 Yr 23 Primary Endpoint: Death, MI, Urgent Revasc 30 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001 Cumulative incidence (%) PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61 MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001 25 20 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization No. at risk MT 441 414 370 322 283 253 220 192 162 127 100 70 37 PCI+MT 447 414 388 351 308 277 243 212 175 155 117 92 53 Registry 166 156 145 133 117 106 93 74 64 52 41 25 13 De Bruyne, et al. New Engl J Med 2012;367:991-1001 24 12

12/8/19 FAME 2: Clinical Outcomes Three Year Rate of Death, MI, or Urgent Revascularization Circulation 2018;137:480-487. 25 FAME 2: Clinical Outcomes Three Year Rate of Death, MI, or Urgent Revascularization Randomized trial N=888 P value Registry N=33 Event PCI+MT=447 MT=441 With FU=166 MACE 10.1% 22% <0.001 12.7% Death 2.7% 3.6% 0.43 3.0% Myocardial Infarction (MI) 6.3% 7.7% 0.41 6.6% Death or MI 8.3% 10.4% 0.28 9.0% Urgent Revascularization 4.3% 17.2% <0.001 6.6% Circulation 2018;137:480-487. 26 13

12/8/19 FAME 2: Clinical Outcomes % of Patients with Class II-IV Angina at each Time Point Circulation 2018;137:480-487. 27 FAME 2: Cost-Effectiveness At three years, the ICER for PCI was $1,600/QALY. Circulation 2018;137:480-487. 28 14

12/8/19 Relationship between FFR and MACE 607 medically treated patients in FAME 2 FFR≤0.63 FFR=0.64-0.77 FFR=0.78-0.86 FFR=0.87-1.0 Barbato, et al. J Am Coll Cardiol 2016;68:2247-55. 29 FAME 2: Five Year Follow-Up Five Year Rate of Spontaneous Myocardial Infarction P=0.04 Medical Therapy PCI Xaplanteris, et al. New Engl J Med 2018;379:250-59. 30 15

12/8/19 Meta-Analysis of FFR-Guided PCI 2,400 patients with stable (or stabilized) CAD from 3 randomized trials comparing FFR-guided PCI with medical therapy Death or MI Death or MI Zimmermann, et al. Eur Heart J 2019;40:180-186. 31 ORBITA Trial n 200 patients with single vessel stenosis >70% and with stable angina n All patients received 6 weeks of medical optimization and then assessment of exercise capacity and angina n Patients then randomized to PCI versus sham PCI n At 6 weeks had repeat assessment of exercise capacity and angina Al-Lamee R, et al. Lancet 2018;391:31-40. 32 16

12/8/19 ORBITA Trial Primary endpoint: change in exercise time at 6 weeks post procedure Al-Lamee R, et al. Lancet 2018;391:31-40. 33 ORBITA Trial Percentage of patients free of patient-reported angina Al-Lamee R, et al. Circulation 2018;138:1780-92. 34 17

12/8/19 ORBITA Trial Relationship of difference in SAQ QOL score and FFR Al-Lamee R, et al. Circulation 2018;138:1780-92. 35 FFR Predicts Quality of Life 891 stable patients treated medically or with PCI in FAME 1 and FAME 2 0.12 seline to 1 month P for P for tr trend end <0.001 (ove verall) 0.1 0.08 0.06 change in EQ5D from base Medical 0.04 Treatment 0.02 0 PCI -0.02 -0.04 Mean ch -0.06 (FFR>0.80) (FFR 0.80–0.70) (FFR 0.69–0.51) (FFR≤0.50) Reference Upper Middle Lower Nishi T, et al. Circulation 2018;138:1797-1804. 36 18

12/8/19 FFR Predicts Quality of Life 706 stable patients treated with PCI in FAME 1 and FAME 2 0.12 year seline to 1 ye Delta FFR = Post PCI FFR – Pre PCI FFR 0.1 0.08 change in EQ5D from base 0.06 0.04 P for P for tr trend end = = 0.009 0.009 0.02 Mean ch 0 Lower Middle Upper (Delta FFR ≤ 0.18) (Delta FFR 0.19–0.32) (Delta FFR ≥ 0.33) -0.02 Nishi T, et al. Circulation 2018;138:1797-1804. 37 ISCHEMIA Trial In patients with stable CAD and at least moderate ischemia on a stress test, is there a benefit to adding coronary angiography, and if feasible, revascularization to optimal medical therapy alone? Hochman, et al. AHA 2019 38 19

12/8/19 ISCHEMIA Trial Stable Patient Moderate or severe ischemia (determined by site; read by core lab) Blinded CCTA CCTA not required, e.g., eGFR 30 to <60 or coronary anatomy previously defined NO Core lab anatomy eligible? Screen failure YES RANDOMIZE INVASIVE Strategy CONSERVATIVE Strategy OMT + Cath + OMT alone Optimal Revascularization Cath reserved for OMT failure Hochman, et al. AHA 2019 39 ISCHEMIA Trial Inclusion Criteria • Age ≥21 years • Moderate or severe ischemia* • Nuclear ≥10% LV ischemia (summed difference score ≥7) • Echo ≥3 segments stress-induced moderate or severe hypokinesis, or akinesis • CMR • Perfusion: ≥12% myocardium ischemic, and/or • Wall motion: ≥3/16 segments with stress-induced severe hypokinesis or akinesis • Exercise Tolerance Testing (ETT) >1.5mm ST depression in >2 leads or >2mm ST depression in single lead at <7 METS, with angina Hochman, et al. AHA 2019 40 20

12/8/19 ISCHEMIA Trial Major Exclusion Criteria • NYHA Class III-IV HF • Unacceptable angina despite medical therapy • EF < 35% • ACS within 2 months • PCI or CABG within 1 year • eGFR <30 mL/min or on dialysis Hochman, et al. AHA 2019 41 ISCHEMIA Trial CCTA Eligibility Criteria Inclusion Criteria • ≥50% stenosis in a major epicardial vessel (stress imaging participants) • ≥70% stenosis in a proximal or mid vessel (ETT participants) Major Exclusion Criteria • ≥50% stenosis in unprotected left main Hochman, et al. AHA 2019 42 21