Thomas Engstrøm, MD, DMSci, PhD Rigshospitalet, University of Copenhagen, Denmark

1. The Third DANishStudy of Optimal AcuteTreatment of Patients with ST-segment Elevation MyocardialInfarctionPRImaryPCI in MULTIvesselDisease - DANAMI3-PRIMULTI Thomas Engstrøm, MD, DMSci, PhD Rigshospitalet, University of Copenhagen, Denmark

2. Participating sites and investigators Rigshospitalet University Hospital Henning Kelbæk Steffen Helqvist Lars Køber Dan Eik Høfsten Lene Kløvgaard Lene Holmvang Erik Jørgensen Kari Saunamäki Frants Pedersen Peter Clemmensen Thomas Engstrøm Aalborg University Hospital Hans-Henrik Tilsted Hansen Jan Ravkilde Svend Eggert Jensen Anton Boel Villadsen Jens Aarøe Bent Raungaard Clinical Event Comité (CEC) Kristian Thygesen Anders Galløe Jørgen Jeppesen Data Safety and Monitoring Board (DSMB) Gorm Bøje Jensen Gunnar Gislasson David Erlinge ClinicalTrials.gov number NCT01960933 DANAMI3-PRIMULTI

3. Disclosures No disclosures with regard to the present trial DANAMI3-PRIMULTI

4. Background IRA 30-50% of STEMI patients have additional stenoses other than the infarct related artery1,2 Current guidelines support culprit vessel PCI only Contemporary studies have, however, suggested preventive revascularisation3,4 Non culprit 1 Jong JA al. Coronary Artery disease 2006 2 Muller DW et al. Am Heart J 1991 3 Wald et al. NEJM 2013 4 Gershlick et al. ESC 2014 DANAMI3-PRIMULTI

5. European guidelines (ESC) Windecker S et al. Eur Heart J 2014 DANAMI3-PRIMULTI

6. I IIa IIb III I IIa IIb III I IIa IIb III American guidelines (ACC/AHA) • PCI of a non-infarct artery at the time of primary PCI in patients without hemodynamic compromise is not indicated B • PCI is indicated in a non-infarct artery at a time separate from primary PCI in patients who have spontaneous symptoms of myocardial ischemia. B • PCI is reasonable in a non-infarct artery at a time separate from primary PCI in patients with intermediate- or high-risk findings on noninvasive testing O´Gara PT S et al. JACC 2013 DANAMI3-PRIMULTI

7. PRAMI – cardiac death, non fatal MI, refractory angina HR 0.35, p<0.001 (95% CI 0.21-0.58) 65% riskreduction 53 N=234 N=231 Wald et al. NEJM 2013 DANAMI3-PRIMULTI

8. Cvlprit – total mortality, recurrent MI, heart failure, revascularisation Gershlick et al. ESC 2014 DANAMI3-PRIMULTI

9. Power calculation One year repeat revascularisation of non-culprit lesions occured in 5-6%1 One year all-cause mortality or nonfatal MI occurred in 12-13%2 Estimated rate of primary endpoint in IRA arm: 18% A relative reduction in the primary endpoint of 30% can be detected with a two-sided alpha level of 0∙05 and a power of 80% by enrolling 618 patients. 1Glaser et al. Circulation 2005 2Lønborg et al. EUR H J 2014 DANAMI3-PRIMULTI

10. DANAMI3-TRIAL PROGRAM • 2239 STEMI < 12 hours Randomise conventional PPCI, iPOST, defer stenting 2212 Successful infarct related artery PCI 627 Multivessel disease (>50% stenosis in non IRA > 2 mm suitable for PCI) Randomise 313 IRA PCI only 314 FFR guided complete revascularisation DANAMI3-PRIMULTI

11. DANAMI3-TRIAL PROGRAM 627 Multivessel disease (>50% stenosis in non IRA > 2 mm suitable for PCI) 313 IRA PCI only 314 FFR guided complete revascularisation 313 Received allocated intervention 0 Did not receive allocated intervention 294 Received allocated intervention 15 PCI failed or not feasible 1 Died before PCI 2 Refused subsequently 2 Other reasons 313 Analysed on intention to treat basis 0 Lost to follow up 314 Analysed on intention to treat basis 1 Lost to follow up (emigration) DANAMI3-PRIMULTI

12. DANAMI3-TRIAL PROGRAM 627 Multivessel disease (>50% stenosis in non IRA > 2 mm suitable for PCI) 313 IRA PCI only 314 FFR guided complete revascularisation 313 Received allocated intervention 0 Did not receive allocated intervention 294 Received allocated intervention 15 PCI failed or not feasible 1 Ded before PCI 2 Refused subsequently 2 Oher reasons 313 Analysed on intention to treat basis 0 Lost to follow up 314 Analysed on intention to treat basis 1 Lost to follow up (emigration) DANAMI3-PRIMULTI

13. Primary endpoint Composite All-cause mortality Nonfatal myocardial infarction Ischemia driven revascularisation of non IRA lesions Assessed when the last included patient had been followed for 1 year DANAMI3-PRIMULTI

14. Baseline characteristics DANAMI3-PRIMULTI

15. Procedural data DANAMI3-PRIMULTI

16. Clinical characteristics DANAMI3-PRIMULTI

17. Medical theraphy at discharge DANAMI3-PRIMULTI

18. Complications DANAMI3-PRIMULTI

19. Primary endpoint DANAMI3-PRIMULTI

20. Individual components of primary endpoint Composite Revascularisation Non fatal MI All cause death DANAMI3-PRIMULTI

21. DANAMI3-PRIMULTI * PCI or CABG DANAMI3-PRIMULTI

22. Endpoints p=0.004 68 p<0.001 52 Event rate (%) p=0.002 p=0.47 40 p=0.03 27 p=0.87 25 p=0.43 p=0.29 18 20 16 15 17 15 11 8 9 7 5 DANAMI3-PRIMULTI

23. Subgroup analysis * there were no events in patients with prior myocardial infarction randomized to complete revascularization DANAMI3-PRIMULTI

24. Contemporary randomised trials DANAMI3-PRIMULTI

25. Contemporary randomised trials DANAMI3-PRIMULTI

26. Conclusions Complete FFR guided revascularisation of multivessel disease in STEMI patients, staged within the index admission, reduced the primary endpoint of all cause death, reinfarction and repeat revascularisation 40% of repeat revascularisations were urgent However, the reduction in the primary endpoint was driven by repeat revascularisations and not by hard endpoints Therefore, although complete revascularisation should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategi of IRA PCI only DANAMI3-PRIMULTI