1. Radial versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome the RIFLE STEACS study Enrico Romagnoli, MD PhD Principal investigators: Enrico Romagnoli, MD PhD Giuseppe Biondi-Zoccai, MD Giuseppe Sangiorgi, MD F R

2. Disclosure Statement of Financial Interest I, Enrico Romagnoli DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. Bleeding complications in patients with acute coronary syndromes are a significant predictor of mortality. We aimed to test whether transradial access for ST elevation myocardial infarction (STEMI) treatment is associated with better outcome when compared to transfemoral approach. RIFLE STEACS - rationale

4. The sample size was computed exploiting the 30-day rate of NACE in STEMI patients in the heparin-treated arm of the HORIZONS-AMI study (12.1%), and retrieving absolute risk reductions from a systematic transradial approach averaging 4.5% stemming from meta-analyses*. RIFLE STEACS – sample size *Agostoni P. et al, J Am Coll Cardiol 2004;44:349-56. Jolly SS, et al. Am Heart J. 2009;157:132-40.

5. RIFLE STEACS – end-points  net adverse clinical events (NACE) at 30 days, defined as the composite of cardiac death, myocardial infarction (MI), target lesion revascularization, stroke, or non- coronary artery bypass graft (non- CABG)-related bleeding.  Non CABG-related bleeding at 30 days (corresponding to type 2, type 3 and type 5 of BARC classification).

6. RIFLE STEACS - flow chart Design DESIGN: Prospective, randomized (1:1), parallel group, multi-center trial. INCLUSION CRITERIA: all ST Elevation Myocardial infarction (STEMI) eligible for primary percutaneous coronary intervention. ESCLUSION CRITERIA: contraindication to any of both percutaneous arterial access. international normalized ratio (INR) > 2.0. 1001 patients enrolled between January 2009 and July 2011 in 4 clinical sites in Italy Clinical follow-up at 1 month in 100% Femoral arm (N=501) Radial arm (N=500) Femoral arm (N=534) Radial arm (N=467) Clinical follow-up at 1 month in 100% Intention-to-treat analysis 4.7% 1.4%

7. overall (1001) Femoral arm (n=501) Radial arm (n=500) p value Age (years) 65±1366±1365±130.344 Female gender 26.7%28.1%25.2%0.317 Body mass index 28±1027±529±140.074 CKD (GRF <60 ml/min/1.73 2 ) 23.8%25.3%22.2%0.156 Diabetes 23.7%24.4%23.0%0.656 LVEF 45±9%45±10%46±9%0.228 Prior MI 14.1%14.2%14.0%1.000 Prior stroke 4.1%4.4%3.8%0.750 Prior revascularization 11.7%10.4%13.0%0.202 Demographic characteristics RIFLE STEACS – population

8. overall (1001) Femoral arm (n=501) Radial arm (n=500) p value Severity of CAD Not significant Single vessel disease Double vessel disease Triple vessel disease 1.1% 54.5% 28.5% 15.9% 1.2% 53.1% 29.7% 16.0% 1.0% 56.0% 27.2% 15.8% 0.789 Killip class I II III IV 67.7% 21.0% 5.2% 6.1% 65.9% 21.5% 5.6% 7.0% 69.6% 20.4% 4.8% 5.2% 0.515 Procedural characteristics RIFLE STEACS – population

9. overall (1001) Femoral arm (n=501) Radial arm (n=500) p value Symptom-balloon time (min) 313±277322±292328±3010.752 SBP at admission (mmHg) 128±28126±28129±270.138 Prior failed thrombolysis 7.6%7.0%8.2%0.477 Heparin dose (U/Kg) 75.6±2175.2±2076.0±220.548 GP IIb/IIIa inhibitors 68.6%69.9%67.4%0.414 Bivalirudin 7.6%7.2%8.0%0.635 Thrombectomy 40.7%40.5%40.8%0.949 Intra aortic balloon pump 8.0%8.4%7.6%0.727 Procedural characteristics RIFLE STEACS – population

10. overall (1001) Femoral arm (n=501) Radial arm (n=500) p value Occlusive lesion (%)59.6%59.7%59.6%1.000 Direct stenting (%) 28.1%27.9%28.2% 0.944 Target Vessel (%) None LMT LAD Cx RCA Graft 1.1% 0.6% 46.8% 16.3% 34.2% 1% 1.2% 0.8% 46.7% 15.0% 35.3% 1.0% 0.4% 47.0% 17.6% 33.0% 1.0% 0.818 Final TIMI flow (%) 0-1 2-3 3.7% 96.3% 3.8% 96.2% 3.6% 96.4% 0.871 Procedural characteristics RIFLE STEACS – population

11. p = 0.003 Net Adverse Clinical Event (NACE) = MACCE + bleeding 30-day NACE rate RIFLE STEACS – results p = 0.029p = 0.026 21.0% 11.4% 7.2% 12.2% 7.8% 13.6%

12. p = 0.003 Net Adverse Clinical Event (NACE) = MACCE + bleeding Major Adverse Cardiac and Cerebrovascular event (MACCE) = composite of cardiac death, myocardial infarction, target lesion revascularization, stroke 30-day NACE rate RIFLE STEACS – results p = 0.029p = 0.026 21.0% 11.4% 7.2% 12.2% 7.8% 13.6%

13. p = 0.020 30-day MACCE rate RIFLE STEACS – results p = 1.000p = 0.604p = 0.725 9.2% 5.2% 1.4% 1.2% 1.8% 1.2% 0.6% 0.8%

14. 30-day bleeding rate RIFLE STEACS – results p = 1.000 12.2% 6.8% 2.6% 5.4% 5.2% p = 0.026 7.8% 47% p = 0.002

15. ORCI 95%p value Female gender 1.5(1.1-2.3)0.037 CKD 2.1(1.4-3.1)0.001 Radial access 0.6(0.4-0.9)0.012 Killip class 1.8(1.5-2.2)0.001 LAD culprit 1.7(1.2-2.6)0.006 TIMI 0 basal 1.4(1.0-2.1)0.073 LVEF <50% 1.6(1.1-2.5)0.025 TIMI 0-1 final 2.4(1.1-5.1)0.024 30-day NACE predictors RIFLE STEACS – results p= 0.002

16. Radial access in patients with STEMI is associated with significant clinical benefit, in terms of both bleeding and cardiac mortality. Radial approach should thus no more be considered a valid alternative to femoral one, but become the recommended access site for STEMI (international guideline). RIFLE STEACS - conclusions

17. Damn Femoral! Hi hi hi, mine was randomized to radial I guess, It’s just not my day

18. RIFLE STEACS – centres Policlinico Casilino Rome Ospedale S. Pertini Rome Policlinico di Modena Modena Università di Torino Turin