Eliano Pio Navarese, MD, PhD Nicolaus Copernicus University, Poland SIRIO MEDICINE network

1. Stable Angina: The best timing of coronary angiography and the role of further investigations onmyocardial ischemia still need to be defined Eliano Pio Navarese, MD, PhD Nicolaus Copernicus University, Poland SIRIO MEDICINE network

2. Very Early vs delayed PCI in NSTE-ACS Background • In NSTE-ACS the superiority of coronary angiography/PCI vsa conservative medical treatment has been shown. • In NSTE-ACS avery early invasive approach (≤ 24 hours) is not proven to be superior to an delayed approach (>24 hour). • Trials showed no advantage of coronary angiography/PCI vs • medical therapy in stable coronary artery disease (CAD). • Which is the best timing of angiography in stable CAD? Navarese, Ann Intern Med 2013

3. PCI vs medical therapy Stepwise diagnostic approach to CAD

4. Guidelines require a Bayesian approach to diagnosis, which uses the results of diagnostic tests along with clinicians’ initial estimates of the disease, termed pre-test probability (PTP). ESC guidelines, EHJ 2013

5. ESC guidelines, EHJ 2013

6. ESC guidelines, EHJ 2013

7. COURAGE trial: Survival Free of Death from Any Cause and Myocardial Infarction Optimal Medical Therapy (OMT) 1.0 0.9 0.8 PCI +OMT 0.7 Hazard ratio: 1.05 95% CI (0.87-1.27) P = 0.62 0.6 0.5 0.0 0 1 2 3 4 5 6 7 Years Number at Risk Medical Therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35 Boden, et al. N Engl J Med 2007

8. Bangalore, Circulation 2012

9. Issues of the Courage trial • Selection bias (randomization after cardiac catheterization) • No sufficient threshold for ischemia (lower risk) 3) No use of contemporary techniques such as FFR and minimal use of DES Rossini, Am J Cardiovasc Dis. 2013

10. * § Cardiac Death Rate (%) 0% 1-5% 5-10% 11-20% >20% *p < 0.0001 % Total Myocardium Ischemic †10,627 Consecutive patients followed 1.9 + 0.6 years. Hachamovitch et al. Circ 1998;

11. Primary endpoint: % with ischemia reduction ≥ 5% myocardium (N=314) COURAGE nuclear substudy II 33.3% p=0.004 Ischemia reduction ≥ 5% 19.8%

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

13. FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD 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 30 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 Primary Outcomes

14. PCI and Relief of Angina Weintraub N Engl J Med 2008.

15. Event risk stratification

16. ESC guidelines, EHJ 2013

17. Granillo, EHJ 2013

18. ClinicalTrials.gov Identifier: NCT01471522

19. Optimal Timing = Optimal Patient Navarese et al. unpublished

20. “Unicuique suum”? Grazie!