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

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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

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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

• f Health: R61/R33 HL139929 (PI)

n Interventional Cardiologist!!

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November 2, 2017

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Brown DL and Redberg RF. Lancet 2018;391:3-4.

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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

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COURAGE: Aim

n To determine whether the addition of PCI to

• ptimal 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.

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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.

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Degree of Ischemia in COURAGE

Shaw, et al. Circulation 2008;117:1283-91.

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Hachamovitch, et al. Circulation 2003;107:2900-06.

Importance of Myocardial Ischemia

With greater degrees of ischemia, there is a survival benefit for PCI P<0.001 10% Ischemic Myocardium

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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)

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Fractional Flow Reserve

Distal Pressure (Pd) Proximal Pressure (Pa)

FFR = Pd / Pa during maximal flow

Pd Pa

Pd / Pa = 60 / 100 FFR = 0.60

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Tonino, et al.J Am Coll Cardiol 2010;55:2816-21.

1329 lesions in the FFR-guided arm of FAME

~35% ~20%

Limitation of Angiography

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DEFER Trial 15 Year Follow-Up

Zimmermann, et al. Eur Heart J 2015;36:3182-8

181 patients with intermediate lesions and FFR≥0.75 randomized to deferral or performance of PCI

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Safety of Deferring PCI Based on FFR

Adapted from: Muller, et al. JACC Cardiovasc Interv 2011;4:1175-82

5 year follow-up of 564 intermediate proximal LAD lesions deferred because FFR≥0.80

No Known CAD Moderate Prox LAD, FFR≥0.80

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New Engl J Med 2009;360:213-24.

FAME 1 Study: One Year Outcomes

3 8.7 9.5 11.1 18.3 1.8 5.7 6.5 7.3 13.2

5 10 15 20 Death MI Repeat Revasc Death/MI MACE Angio-Guided FFR-Guided

p=0.02 p=0.04 %

~40% ¯ ~35% ¯ ~30% ¯ ~35% ¯ ~30% ¯ 1,005 patients with multivessel CAD randomized to FFR or Angio-guided PCI

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FFR-Guided Angio-Guided 730 days 4.5%

Pijls, et al. J Am Coll Cardiol 2010;56:177-184

FAME Study: Two Year Outcomes

Death/MI was significantly reduced from 12.9% to 8.4% (p=0.02) Survival Free of MACE

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FAME: Economic Evaluation

Circulation 2010;122:2545-50.

Bootstrap Analysis

FFR-guided PCI saved >$2,000 per patient at one year compared to Angio- guided PCI

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FAME 2

Death and MI in the COURAGE study

Boden et al., New Engl J Med 2007;356:1503-16.

Implications of FAME

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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

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FAME 2

Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220

FFR in all target lesions

When all FFR > 0.80 (n=332) MT At least 1 stenosis with FFR ≤ 0.80 (n=888)

Randomization 1:1

PCI + MT MT

Primary Endpoint: Death, MI or Urgent Revascularization at 2 Yr

Registry

50% randomly assigned to FU

27%

Randomized Trial

73%

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Primary Endpoint: Death, MI, Urgent Revasc

5 10 15 20 25 30

Cumulative incidence (%)

166 156 145 133 117 106 93 74 64 52 41 25 13 Registry 447 414 388 351 308 277 243 212 175 155 117 92 53 PCI+MT 441 414 370 322 283 253 220 192 162 127 100 70 37 MT

• No. at risk

1 2 3 4 5 6 7 8 9 10 11 12

Months after randomization MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001 PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001

De Bruyne, et al. New Engl J Med 2012;367:991-1001

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FAME 2: Clinical Outcomes

Three Year Rate of Death, MI, or Urgent Revascularization

Circulation 2018;137:480-487.

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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.

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FAME 2: Clinical Outcomes

% of Patients with Class II-IV Angina at each Time Point

Circulation 2018;137:480-487.

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FAME 2: Cost-Effectiveness

At three years, the ICER for PCI was $1,600/QALY.

Circulation 2018;137:480-487.

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Relationship between FFR and MACE

607 medically treated patients in FAME 2

Barbato, et al. J Am Coll Cardiol 2016;68:2247-55. FFR=0.87-1.0 FFR=0.64-0.77 FFR=0.78-0.86 FFR≤0.63

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FAME 2: Five Year Follow-Up

Five Year Rate of Spontaneous Myocardial Infarction

Xaplanteris, et al. New Engl J Med 2018;379:250-59.

P=0.04 Medical Therapy PCI

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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

Zimmermann, et al. Eur Heart J 2019;40:180-186.

Death or MI Death or MI

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ORBITA Trial

n 200 patients with single vessel stenosis

>70% and with stable angina

n All patients received 6 weeks of medical

• ptimization 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.

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ORBITA Trial

Al-Lamee R, et al. Lancet 2018;391:31-40.

Primary endpoint: change in exercise time at 6 weeks post procedure

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ORBITA Trial

Percentage of patients free of patient-reported angina

Al-Lamee R, et al. Circulation 2018;138:1780-92.

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ORBITA Trial

Relationship of difference in SAQ QOL score and FFR

Al-Lamee R, et al. Circulation 2018;138:1780-92.

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FFR Predicts Quality of Life

891 stable patients treated medically or with PCI in FAME 1 and FAME 2

Nishi T, et al. Circulation 2018;138:1797-1804.

• 0.06
• 0.04
• 0.02

0.02 0.04 0.06 0.08 0.1 0.12

Reference Upper Middle Lower

Mean ch change in EQ5D from base seline to 1 month

(FFR>0.80) (FFR≤0.50) (FFR 0.80–0.70) (FFR 0.69–0.51)

P for P for tr trend end <0.001 (ove verall) Medical Treatment PCI

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FFR Predicts Quality of Life

706 stable patients treated with PCI in FAME 1 and FAME 2

Nishi T, et al. Circulation 2018;138:1797-1804. Mean ch change in EQ5D from base seline to 1 ye year

• 0.02

0.02 0.04 0.06 0.08 0.1 0.12

Lower Middle Upper

(Delta FFR≥0.33) (Delta FFR≤0.18) (Delta FFR 0.19–0.32)

P for P for tr trend end = = 0.009 0.009 Delta FFR = Post PCI FFR – Pre PCI FFR

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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?

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ISCHEMIA Trial

Stable Patient Moderate or severe ischemia (determined by site; read by core lab) CCTA not required, e.g., eGFR 30 to <60 or coronary anatomy previously defined Blinded CCTA Core lab anatomy eligible? RANDOMIZE Screen failure INVASIVE Strategy OMT + Cath + Optimal Revascularization CONSERVATIVE Strategy OMT alone Cath reserved for OMT failure NO YES Hochman, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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
• r >2mm ST depression in single lead at <7 METS, with angina

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Primary Endpoint:

n Time to CV death, MI, hospitalization for unstable angina, heart

failure or resuscitated cardiac arrest

Major Secondary Endpoints:

n Time to CV death or MI n Quality of Life

Other Endpoints include:

n All-Cause Death n Net clinical benefit (stroke added to primary endpoint) n Components of primary endpoint

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Characteristic Total INV CON

Baseline Inducible Ischemia* Severe 54% 53% 55% Moderate 33% 34% 32% Mild/None 12% 12% 12% Uninterpretable 1% 1% 1%

Core lab adjudicated degree of ischemia

• n non-invasive testing

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Cardiac Catheterization Revascularization

12% 95% 96% 9% 28% 76%79% 80% 23% 7%

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Procedural Myocardial Infarction

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Spontaneous Myocardial Infarction

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ISCHEMIA Trial

Hochman, et al. AHA 2019

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ISCHEMIA Trial

Spertus, et al. AHA 2019

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ISCHEMIA Trial

Hochman, et al. JAMA Card 2019;4:273-86.

Baseline angina frequency in randomized patients in ISCHEMIA

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ISCHEMIA Trial

Hochman, et al. AHA 2019

Pre-specified subgroup analyses for interaction on the primary endpoint

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Asymptomatic Patients in FAME 2

Asymptomatic and Med Rx Symptomatic and Med Rx Symptomatic and PCI Asymptomatic and PCI Asymptomatic patients treated medically had significantly higher death/MI

Fournier, et al. J Am Coll Cardiol 2019;74:1642-44.

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Asymptomatic Patients in FAME 2

Asymptomatic patients treated medically had significantly higher death/MI

Fournier, et al. J Am Coll Cardiol 2019;74:1642-44. p = 0.022

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Impact of PCI in Stable CAD

ISCHEMIA FAME 2 No ∆ Mortality No ∆ Mortality ↓ Spontaneous MI ↓ Spontaneous MI ↓ Hosp. for unstable ↓ Hosp. for urgent angina revascularization ↓ Angina at 3 years ↓ Angina at 3 years

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Spectrum of Stable CAD

Scheidt: Basic Electrocardiography; 1986 Adapted from: Frank H. Netter, M.D.

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Approach to Stable CAD

n Initial attempt at controlling symptoms with

medical therapy alone.

n If the patient cannot tolerate medical therapy,

has refractory symptoms, or prefers to avoid medications, an initial approach with FFR- guided revascularization is reasonable.

n Longer term follow-up from ISCHEMIA and

substudy analyses will further inform practice.

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