Journal : Evidence Review PCI : Role of FFR

1. Journal : Evidence Review PCI : Role of FFR Dr Binjo J Vazhappilly SR Cardiology MCH Calicut

2. FFR is defined as the ratio of flow in stenoticartery to flow in same artery in the absence of stenosis. • FFR is calculated as the ratio of mean pressure distal (Pd) to stenosisto Aortic pressure (Pa ) , during maximal hyperemia.

3. Validation studies of FFR JACC Vol. 55, No. 3, 2010

4. 2011 ACC/AHA/SCAI Guideline for PCI Class II a FFR is reasonable to assess angiographic intermediate coronary lesions (50% to 70% diameter stenosis) and can be useful for guiding revascularization decisions in patients with Stable IHD.

5. FFR in SCAD : 2013 ESC guidelines

6. DEFER study • Aim :To investigate whether FFR discriminates pts in whom PTCA is appropriate among pts referred for PTCA , without documented ischemia. • Primary end point: Absence of adverse cardiac events ( all-cause mortality, MI , CABG, coronary angioplasty), during 24 months of follow-up. • Study done in multiple centers in Netherlands , Spain , Belgium , Germany, South korea , Japan. • 5 year follow-up also done. G. Jan Willem Bech, MD; Bernard De Bruyne, MD, PhD; Nico H.J. Pijls MD et al Circulation 2001;103:2928-2934

7. Deferral of PTCA (167) FFR < 0.75 (68) PTCA DEFERStudy: Flow Chart Patients scheduled for PCI without Proof of Ischemia (n=325) Randomization Performance of PTCA (158) FFR  0.75 (91) FFR  0.75 (90) FFR < 0.75 (76) PTCA No PTCA PTCA PERFORM Group DEFER Group REFERENCE Group

8. Event Free survival : 2Yrs Circulation 2001;103

9. Free from angina Circulation 2001;103

10. Event free survival (%) : 5 Yrs 100 75 78.8 72.7 64.4 Defer 50 p=0.52 p=0.03 Perform p=0.17 25 Reference (FFR < 0.75) 0 0 1 2 3 4 5 Years of Follow-up JACC Vol. 49, No. 21, 2007

11. Defer group Perform group Reference group Freedom from chest pain 100% *p 0.028 **p <0.001 ***p 0.021 * * * * * 80% * * *** 60% 40% 20% 0% baseline 1month 1 year 2 year 5 year FFR > 0.75 FFR > 0.75 FFR < 0.75 JACC Vol. 49, No. 21, 2007

12. Cumulative Events After 5 Yrs

13. DEFER study conclusions • Compared with medical treatment, PTCA in pts with FFR > 0.75 did not reduce adverse cardiac events or improvement in functional class. • In pts with FFR < 0.75 , PTCA resulted in significant improvement in functional class. • Lesions at greatest risk of causing cardiac death or AMI are those that are functionally significant ( FFR < 0.75) and risk persists even after PCI.

14. Outcomes after FFR based deferral of coronary intervention in intermediate coronary lesions

15. FAME (FFR Vs Angiography for Multivessel Evaluation) Study • In the FAME Study, 1005 patients with multivessel CAD were randomly assigned to FFR-guided PCI or angiography-guided PCI with DES and followed for one year. • Primary end point was rate of major adverse cardiac events at 1 yr : composite of death, MI and repeat revascularization. • Randomised multicenter study in 20 US and European centers. n engl j med 360;3 january 15, 2009

16. FAME Study Design Patient with lesions ≥ 50% in at least 2 of the 3 major epicardial vessels Indicate all lesions ≥ 50% amenable for stenting Randomization Angiography-guided PCI FFR-guided PCI Stent only those stenoses with FFR ≤ 0.80 Stent all indicated stenoses 1-year follow-up Exclusion criteria: LM disease, Previous CABG MI < 5 days Pregnancy, Life expectancy < 2 years n engl j med 360;3 january 15, 2009

17. FAME study: Procedural Results

18. FAME study: Adverse Events at 1 year

19. FFR-guided FAME study: Event-free Survival absolute difference in MACE-free survival Angio-guided 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.3%

20. End points at 2 years JACC :Vol. 56, No. 3, 2010

21. FAME 2 • Aim: To compare clinical outcomes of FFR- guided contemporary PCI plus best available medical therapy (MT) versus MT alone in patients with stable CAD. • Primary end points : Composite of all cause death ,MI, unplanned hospitalization with urgent revascularization. • The trial was conducted at 28 sites in Europe and North America.

22. Patient recruitment was stopped on January 15, 2012, owing to a highly significant difference in incidence rates of primary end point between the PCI and medical- therapy groups. • Between May 15, 2010 and January 15, 2012, a total of 1220 patients were enrolled in the study.

23. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Flow Chart 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 (n=332) At least 1 stenosis with FFR ≤ 0.80 (n=888) Randomization 1:1 PCI + MT MT MT 27% 73% 50% randomly assigned to FU Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

24. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Primary Outcomes PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001 30 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 Cumulative incidence (%) 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

25. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Death from any Cause PCI+MT vs. MT: HR 0.33 (0.03-3.17); p=0.31 30 PCI+MT vs. Registry: HR 1.12 (0.05-27.33); p=0.54 25 MT vs. Registry: HR 2.66 (0.14-51.18); p=0.30 20 Cumulative incidence (%) 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization No. at risk MT 441 423 390 350 312 281 247 219 188 154 122 90 54 PCI+MT 447 423 396 359 318 288 250 220 183 163 122 95 54 Registry 166 156 145 134 118 107 96 76 67 55 43 27 13

26. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Myocardial Infarction 30 PCI+MT vs. MT: HR 1.05 (0.51-2.19); p=0.89 PCI+MT vs. Registry: HR 1.61 (0.48-5.37); p=0.41 25 MT vs. Registry: HR 1.65 (0.50-5.47); p=0.41 20 Cumulative incidence (%) 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization No. at risk MT 441 421 386 341 304 273 239 212 182 148 117 85 48 PCI+MT 447 414 388 352 309 278 244 214 177 157 119 94 54 Registry 166 156 145 134 118 107 95 75 65 53 42 26 13

27. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Urgent Revascularization 30 PCI+MT vs. MT: HR 0.13 (0.06-0.30); p<0.001 PCI+MT vs. Registry: HR 0.63 (0.19-2.03); p=0.43 25 MT vs. Registry: HR 4.65 (1.72-12.62); p=0.009 20 Cumulative incidence (%) 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization No. at risk MT 441 414 371 325 286 256 223 195 164 129 101 71 38 PCI+MT 447 421 395 356 315 285 248 217 180 160 119 93 53 Registry 166 156 145 133 117 106 94 75 65 53 42 26 13

28. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Patients with urgent revascularization Myocardial Infarction 21.4% 51.8% 26.8% Unstable angina +evidence of ischemia on ECG

29. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Patients with Angina Class II to IV PCI+MT PCI+MT PCI+MT PCI+MT MT MT MT MT Baseline Registry Registry Registry Registry P<0.001 30 days P=0.002 P=0.002 6 months P=0.073 12 months 0 20 40 60 80 Percentage of patients with CCS II to IV, %

30. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Conclusions • In patients with stable coronary artery disease, FFR-guided PCI, improve patient outcome as compared with medical therapy alone. • This improvement is driven by a dramatic decrease in the need for urgent revascularization for ACS. • In patients with functionally non-significant stenosesmedical therapy alone resulted in an excellent outcome, regardless of the angiographic appearance of the stenoses.

31. Value of FFR in making decisions about bypass surgery for equivocal LMCA disease . • Was a 2 centre prospective , single cohort follow up study. • FFR of LMCA was determined in 54 consecutive pts with angiographically equivocal disease. • If FFR was > 0.75, medical treatment was chosen and if FFR was < 0.75, surgical treatment was chosen. Heart 2001; 86:547–552 G J W Bech, H Droste, N H J Pijls et al

32. In 24 pts (44%), FFR was > 0.75 and medical treatment was chosen & in 30 pts (56%), FFR was < 0.75 and bypass surgery was performed. • Survival among pts at 3 yrs of follow up was 100% in medical group and 97% in surgical gp. • Event-free survival was 76% in medical gp and 83% in surgical gp. Heart 2001; 86:547–552 G J W Bech, H Droste, N H J Pijls et al

33. Long-Term Outcome After FFR Guided Treatment in Patients With Angiographically Equivocal LMCA Stenosis • 213 pts with an angiographically equivocal LMCA stenosis, FFR measurements were performed. • If FFR was ≥ 0.80, patients were treated medically or another stenosis was treated by coronary angioplasty ( n 138). • When FFR was < 0.80, CABG was performed (n 75). • 5-year survival estimates were 89.8% in nonsurgical gp and 85.4% in surgical gp (P = 0.48). • The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P = 0.50) Circulation. 2009;120:1505-1512 , MichalisHamilos, Olivier Muller et al

34. FFR for assessment of Nonculprit coronary artery stenoses in patients with Acute MI. • Aim : To investigate reliability of FFR of nonculprit coronary stenoses during PCI in acute MI. • 101 pts undergoing PCI for acute MI were prospectively recruited. • The FFR measurements in 112 nonculpritstenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. • The FFR value of nonculpritstenoses did not change between the acute and follow-up (0.77 ± 0.13 vs 0.77 ± 0.13, respectively, p NS). JACC : V O L . 3 , N O . 1 2 , 2 0 1 0 ArgyriosNtalianis, Jan-Willem Sels et al

35. Physiological evaluation of provisional side-branch intervention for bifurcation lesions using FFR • Aim : To evaluate functional outcomes of FFR -guided jailed sidebranch (SB) intervention strategy. • 110 pts were consecutively enrolled and SB FFR was measured in 91 pts. • SB intervention was allowed when FFR was < 0.75. • FFR measurement was repeated after SB intervention and at 6-month follow-up angiography European Heart Journal (2008) 29, 726–732Koo , Park et al

36. In 26 of 28 SB lesions with FFR < 0.75, balloon angioplasty was performed and FFR 0.75 was achieved in 92% of the lesions. • During follow-up, there were no changes in SB FFR in lesions with (0.86 ± 0.05 to 0.84 ± 0.01, P = 0.4) and without SB angioplasty (0.87±0.06 to 0.89 ± 0.07, P = 0.1). • Functional restenosis (FFR ,0.75) rate was only 8% (5/65). European Heart Journal (2008) 29, 726–732Koo , Park et al

37. Clinical outcomes of were compared with 110 pts with similar bifurcation lesions treated without FFR-guidance, there was no difference in 9-month cardiac event rates (4.6 vs. 3.7%, P = 0.7) between two gps. • Cardiac events were defined as cardiac death, myocardial infarction, or target vessel revascularization European Heart Journal (2008) 29, 726–732Koo , Park et al

38. Summary • FFR is useful to assess angiographic intermediate coronary lesions and can guide revascularization decisions in pts with stable IHD. • Medical therapy is appropriate when FFR ≥ 0.8. • Revascularization is recommended in lesions where FFR < 0.8 and patient having evidence for ischemia. • FFR is helpful in making decision in intermediate LMCA disease . • FFR can assess nonculprit lesions during ACS. • FFR is useful in intervention of bifurcation lesions .