Management of stable CAD FFR guided therapy: the new gold standard Suleiman Kharabsheh, MD Director; CCU, Telemetry and CHU Associate professor of Cardiology, Alfaisal Univ. KFHI - KFSHRC
Should patients with stable ischemic heart disease undergo revascularization?
SIHD The answer is less clear for these patients than for patients with ACS Benefits may be limited to the improvement of angina (has been recently challenged, ORBITA)! Uncertainty about the benefit of routine revascularization in this cohort (COURAGE)
Risk stratification Only patients with documented myocardial ischaemia involving 10% of the LV myocardium have a lower CV and all-cause mortality when revascularization is performed Revascularization may increase mortality in patients with ischaemia involving,10% of the myocardium Eur Heart J 2011;32:1012 1024. Circulation 2003;107:2900 2907
Circulation 2003;107:2900 2907 Relationship between cardiac mortality and extent of myocardial ischemia *P < 0.02
Annual Mortality with Medical Therapy Circulation 1994; 89:2015 2025.
MEDICAL THERAPY FOR ALL Lipid management Blood pressure management Physical activity Weight management Smoking cessation Antiplatelet therapy Beta-blockers for patients with normal LVF after ACS, and for those with an ejection fraction of < 40% ACE-I or ARB for patients who have hypertension, diabetes, LVEF < 40% or CKD Annual influenza vaccination Anti-ischemic medications (betablockers, calcium channel blockers, nitrates) for relief of symptoms
Aim of the COURAGE Trial To determine whether PCI plus OMT reduces the risk of death or nonfatal MI in symptomatic patients with stable CAD, as compared with OMT alone. 2,287 patients included in COURAGE, were a low-risk subset of the more than 35,000 patients initially evaluated 2.5 to 7 year (mean 4.6 year) follow-up
Baseline Nuclear Imaging* Reversible Perfusion Defects Single 23% Multiple 67% LVEF% 61% (mean) *60% of subjects had baseline nuclear stress testing
Baseline Angiographic Disease Severity 31% 30% 3 VD 1 VD 2 VD 1 VD 2 VD 3 VD 39%
Survival Free of Death from Any Cause and Myocardial Infarction 1.0 Optimal Medical Therapy (OMT) 0.9 0.8 0.7 0.6 0.5 0.0 PCI + OMT Hazard ratio: 1.05 95% CI (0.87-1.27) P = 0.62 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35 7
Survival Free of Hospitalization for ACS 1.0 0.9 0.8 OMT PCI + OMT 0.7 0.6 0.5 Hazard ratio: 1.07 95% CI (0.84-1.37) P = 0.56 0.0 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1025 956 833 662 418 236 127 PCI 1149 1027 957 835 667 431 246 134 7
Freedom from Angina During Long-Term Follow-up Characteristic PCI + OMT OMT CLINICAL Angina free no. Baseline 12% 13% 1 Yr 66% 58% 3 Yr 72% 67% 5 Yr 74% 72% The comparison between the PCI group and the medical-therapy group was significant at 1 year ( P<0.001) and 3 years (P=0.02) but not at baseline or 5 years.
ORBITA trial 230 enrolled Dec 2013 - Jul 2017 in 5 UK sites Medical optimization phase 30 patients exited 200 patients randomized PCI (n=105) Placebo (n=95) Blinded follow-up phase 4 patients did not complete follow-up Follow-up (n=105) Follow-up (n=91)
Stenosis severity PCI n = 105 Placebo n = 95 P Area stenosis by QCA (%) 84.6 84.2 0.781 (SD 10.2) (SD 10.3) FFR 0.69 0.69 0.778 (SD 0.16) (SD 0.16) ifr 0.76 0.76 0.751 (SD 0.22) (SD 0.21)
Change in exercise time (seconds) Primary endpoint result Change in total exercise time 40 35 30 25 20 15 28.4 (SD 86.3) p=0.001 +16.6 sec (-8.9 to 42.0) p=0.200 10 5 0 PCI 11.8 (SD 93.3) p=0.235 Placebo Error bars are standard errors of the mean
Secondary endpoint results Blinded evaluation of ischaemia reduction Peak stress wall motion index score Pre-randomization Follow-up Δ (Pre-randomization to follow-up) Difference in Δ between arms PCI n = 80 1.11 (0.18) 1.03 (0.06) -0.08 (0.17) p<0.0001 Placebo n = 57 1.11 (0.18) 1.13 (0.19) 0.02 (0.16) p=0.433-0.09 (-0.15 to -0.04) p=0.0011
Conclusions ORBITA is the first placebo-controlled randomized trial of PCI in stable angina PCI significantly reduced ischemic burden as assessed by stress echo In this single vessel, angiographically guided trial there was no difference in exercise time increment between PCI and placebo
Why Do We Need FFR? The noninvasive test is a useful gatekeeper to decide which patients warrant invasive coronary angiography MPI lacks spatial resolution, particularly in MVD In the majority of patients undergoing CAG /PCI, noninvasive stress imaging has not been performed (50%). JAMA. 2008;300:1765 1773.
Concept of FFR Maximum flow down a vessel in the presence of a stenosis compared to the maximum flow in the hypothetical absence of the stenosis Pijls and De Bruyne, Coronary Pressure Kluwer Academic Publishers, 2000
Advantages of FFR FFR is extremely reproducible Independent of hemodynamic changes Narrow cutoff range (0.75-0.8) Superb spatial resolution Specific for epicardial stenosis Independent of the microvasculature Accounts for collateral flow
Is Coronary Angio alone a good tool to judge CAD severity? Fractional Flow Reserve Versus Angiography for Multi-vessel Evaluation (FAME) trial
FAME Trial
FAME primary end point
FAME
Approximately one fourth of the deferred lesions appeared >70% narrowed on visual interpretation of the angiogram!
Is deferral of PCI safe in SCAD if FFR > 0.75?
DEFER study 325 patients 181 patients FFR > 0.75 => No ischaemia Randomisation 144 patients FFR < 0.75 => Ischaemia PTCA 144 patients Performance of PTCA 90 patients 2 yr follow-up Deferral of PTCA 91 patients 2 yr follow-up Bech et al, Circulation 2001
DEFER Study Result at 5 years
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 and 5 years
Importance of Ischemia COURAGE FAME 2 No/limited Ischemia 69% 100% of randomized patients had (extensive) myocardial Ischemia Courtesy of: Bernard De Bruyne Mean FFR value of 0.68 in large epicardial arteries
Primary Endpoint: Death, MI, Urgent Revasc 25 20 15 10 5 Cumulative incidence (%) 30 No. at risk MT PCI+MT Registry 0 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001 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 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization 441 414 370 322 283 253 220 192 162 127 100 70 37 447 414 388 351 308 277 243 212 175 155 117 92 53 166 156 145 133 117 106 93 74 64 52 41 25 13 De Bruyne, et al. New Engl J Med 2012;367:991-1001
FAME 2 2 years 8.1% in the PCI group vs 19.5% in the MT group (HR 0.39, P <0.001)
FAME 2 2 years After 2 years, 179 patients (40.6%) in the medical - therapy group had crossed over to undergo PCI, whereas 36 patients (8.1%) in the PCI group had undergone repeat revascularization (HR 0.16, P < 0.001)
3 Year Clinical Outcome and Cost-Effectiveness of FFR- Guided PCI in Stable Patients with Coronary Artery Disease: FAME 2 Trial William F. Fearon, MD, Takeshi Nishi, MD, Bernard De Bruyne, MD, PhD, Derek B. Boothroyd, PhD; Emanuele Barbato, MD, PhD, Pim Tonino, MD, PhD, Peter Ju ni, MD, Nico H.J. Pijls, MD, PhD, and Mark A. Hlatky, MD for the FAME 2 Trial Investigators
Objective Evaluate the long-term clinical outcomes, effects on quality of life, and cost-effectiveness of FFR-guided PCI versus medical therapy alone in patients with stable coronary artery disease enrolled in the FAME 2 trial.
Results: Clinical Outcome Three Year Rate of Death, MI, or Urgent Revascularization *P value compares PCI + MT patients with MT patients
Results: Quality of Life % of Patients with Class II-IV Angina at each Time Point % with CCS II-IV Angina
Results: Costs
Importance of Myocardial Ischemia With greater degrees of ischemia, there is a survival benefit for PCI P<0.001 Hachamovitch, et al. Circulation 2003;107:2900-06.
Conclusion Ischemic Burden is the key determinant in Stable CAD patients Ischemia-guided coronary revascularization (FFR) improves long term outcomes while reducing cost compared with angiography guided approach
Inaccuracy of Radionuclide Imaging JACC 2010;3:315-7.
What's in the Pipeline ISCHEMIA STUDY