1. Determination of the RAdial versus GrOiN coronary angioplasty The Result of DRAGON Trial Shigeru Saito, MD Department of Cardiology and Catheterization Laboratory Shonan Kamakura General Hospital, Kamakura, Japan on behalf of Dragon Trial investigators

2. Disclosure Statement of Financial Interest Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit None TERUMO, Boston Scientific None Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany

3. Background this study TRI is getting more popular all around the world. However, it is not yet clear whether ad-hoc TRI strategy can provide clinical outcomes similar to TFI strategy. Thus, we initiated DRAGON trial to show the effectiveness of ad-hoc TRI strategy in the real world.

4. Objective of this study To determine the clinical benefit of the transradial approach compared to the transfemoral approach in patients, who receive percutaneous coronary intervention in the real world practice. The benefit is shown based on the non-inferiority of TRI in terms of clinical effectiveness at 1 year and on the superiority of TRI to reduce the major bleeding complications at 7 days compared to TFI.

5. Primary Investigators Shigeru SAITO, MD Yong HUO, MD Honorary Primary Investigator Runlin GAO, MD Ferdinard KIEMENEIJ, MD Steering CommitteeShigeru SAITO Junbo GE Yujie ZHOU Guosheng FU Jian’an WANG Bo XU Yong HUO Shubin QIAO Yaling HAN Jiyan CHEN Haichang WANG Wei LI Biostatistic AnalysisMedical Research & Biometrics Center National Center for Cardiovascular Diseases Cardiovascular Institute & Fuwai Hospital SponsorTERUMO CRO/DM/CLCCRF Study Organization

6. Endpoints  Primary Endpoint  Major Adverse Cardiac or Cerebrovascular Event (MACCE) free rate at 12 months  Major Secondary Endpoint  Major bleeding complication (BARC definition type 3 or 5) free rate at 7 days

7. Statistical considerations This study had 80% statistical powered to demonstrate the non-inferiority (NI margin=5%) of TRI on primary endpoint (MACCE-free rate at 1 year) comparing to TFI And also powered (>85%) to demonstrate the superiority of TRI on major secondary endpoint (bleeding-free rate at 7 days) comparing to TFI Intention-To-Treat (ITT) principle had been used for the primary analysis

8. Enrollments Patients who had PCI were the target population

9. TRI (N=1,212) TFI (N=527) P-value Male (%)72.5%64.7%0.001 Age (yrs)61.1±10.862.9±10.90.001 Height (cm)168.6±6.9166.9±7.5<0.001 Weight (Kg)71.2±10.669.0±10.8<0.001 BMI (Kg/m2)25.0±3.124.6±3.10.049 Heart Rate (Beats/m)72.1±11.872.4±13.00.626 Current Smoker (%)37.8%31.3%0.033 Baseline characteristics (PCI population before adjustment)

10. Disease history (PCI population before adjustment) TRI (N=1,212) TFI (N=527) P-value Hypertension (%)58.7%60.9%0.380 Hyperlipidemia (%)15.2%11.8%0.043 Diabetes (%)25.0%24.9%0.950 Prior MI (%)11.4%13.7%0.185 Prior PCI (%)12.1%14.2%0.231 Prior CABG (%)0.2%3.2%<0.001 Cerebrovascular Disease (%)11.0%12.3%0.415 Peripheral vascular Disease(%)1.4%0.9%0.424 Family history of CAD (%)8.8%8.3%0.744

11. Baseline diagnosis (PCI population before adjustment) TRI (N=1,212) TFI (N=527) P-value Silent Myocardial Ischemia (%)1.7%1.5%0.746 Angina (%)64.0%55.6%0.001 MI (%)34.2%42.9%0.001 LVEF (%)59.1±9.258.5±9.60.329 NYHA class (%) Ⅰ 63.2%56.9%0.049 Ⅱ 33.3%36.9% Ⅲ 3.4%6.3% Ⅳ 0.2%0.0% Killip class (%) Ⅰ 83.4%78.3%0.345 Ⅱ 12.6%16.9% Ⅲ 3.4% Ⅳ 0.6%1.4%

12. Kaplan-Meier curve MACCE-free rate at 12 months (PCI population before adjustment) TRI 1212 1168 1147 1143 1133 1125 1114 TFI 527 494 483 475 467 462 459 HR = 0.707 (95% CI: 0.443-1.129) P-value (log-rank test): 0.144 Pts. at risk TRI TFI

13. Primary Endpoint MACCE-free rate at 12 months The non-inferiority was met as the upper 95% confidence bound is less than the non- inferiority margin (5%) Difference [95% CI] TRI (N=1,212) TFI (N=527) Difference [95% CI] TFI-TRI P-value (non- inferiority) 96.1%94.4% -1.7% [-4.0%; 0.6%] <0.001 TRI is betterTFI is better Non-inferiority -5% 0% 5% (PCI population before adjustment)

14. Major bleeding complication-free rate at 7 days (major 2 nd endpoint) There was no significant difference between the TRI and TFI group on the 2 nd endpoint among the unadjusted observed data Difference [95% CI] TRI (N=1212) TFI (N=527) Difference [95% CI] TFI-TRI P-value (superiority) 99.8%99.4% -0.4% [-1.1%; 0.3%] 0.131 TRI is better TFI is better -3% 0% 3% (PCI population before adjustment)

15. The 23 baseline covariates had been included in the PS model were pre-specified without any knowledge of clinical outcomes (both efficacy & safety) HL test had a P=0.857 IPW (inverse probability weighting) had been carried out Since we unexpectedly found imbalanced randomized allocation, we did propensity score analysis based on 23 baseline covariates.

16. TRI (N=1,212) TFI (N=527) P-value Male (%)70.4%70.5%0.928 Age (yrs)61.54 ±12.8561.15 ±20.620.467 Height (cm)168.09 ±8.34167.71 ±13.650.349 Weight (Kg)70.74 ±12.8270.39 ±21.400.573 BMI (Kg/m2)24.99 ±3.7824.97 ±5.830.926 Heart Rate (Beats/m) 72.12 ±13.9772.65 ±24.250.378 Current Smoker (%) 37.1%33.3%0.012 Baseline characteristics (After IPW adjustment)

17. TRI (N=1,212) TFI (N=527) P-value Hypertension (%)59.0%56.1%0.084 Hyperlipidemia (%)13.9%13.1%0.458 Diabetes (%)25.4%24.4%0.492 Prior MI (%)12.2%11.1%0.301 Prior PCI (%)12.3%13.4%0.319 Prior CABG (%)0.8%1.1%0.323 Cerebrovascular Disease (%)10.7%12.9%0.039 Peripheral vascular Disease(%)1.2% 0.894 Family history of CAD (%)7.9%7.2%0.482 Disease history (After IPW adjustment)

18. TRI (N=1,212) TFI (N=527) P-value Silent Myocardial Ischemia (%) 1.7%1.8%0.797 Angina (%) 61.0%62.7%0.283 MI (%) 37.4%35.5%0.248 LVEF (%)58.63 ±11.2458.61 ±16.920.973 NYHA class (%) Ⅰ 63.3%64.5%0.010 Ⅱ 33.0% 29.7% Ⅲ 3.6%5.8% Ⅳ 0.2%0.0% Baseline diagnosis (After IPW adjustment)

19. TRI (N=1,212) TFI (N=527) P-value Killip class (%) Ⅰ 82.7%76.8%0.007 Ⅱ 13.4%18.2% Ⅲ 3.5%2.9% Ⅳ 0.4% 2.0% Baseline diagnosis (cont.) (After IPW adjustment)

20. TRI (N=1,212) TFI (N=527) P-value Lesion number 1.3±0.71.4±1.20.054 Procedural success (%) 99.6%98.7%0.007 Operative complication (%) 1.6%3.3%0.001 Procedure time (min) 59.1±35.360.1±62.30.516 Procedural information (After IPW adjustment)

21. TRI (N=1,611) TFI (N=729) P-value TYPE (%) A1.8%2.0%0.939 B125.2%25.6% B27.7%7.4% C 65.3%65.0% Bifurcation lesion (%) 9.4%9.6%0.864 CTO (%) 6.1% 6.3%0.754 Pre-op TIMI 0&1 (%)23.9%30.9% Number of stents/lesion 1.2±0.71.2±1.10.515 Lesion characteristics (PCI population before adjustment)

22. HR = 0.928 (95% CI: 0.672-1.280) P-value (log-rank test): 0.822 Kaplan-Meier curve MACCE-free rate at 12 months (After IPW adjustment) TRI 1212 1168 1147 1143 1133 1125 1114 TFI 527 494 483 475 467 462 459 Pts. at risk TRI TFI

23. Difference [95% CI] TRI is better TFI is better Non-inferiority -5% 0% 5% TRI (N=1,212) TFI (N=527) Difference [95% CI] TFI-TRI P-value (non- inferiority) 95.8%95.5% -0.3% [-1.7%; 1.0%] <0.001 Primary Endpoint MACCE-free rate at 12 months (After IPW adjustment) The non-inferiority was met as the upper 95% confidence bound is less than the non- inferiority margin (5%)

24. The superiority is met (after propensity score- IPW adjustment) as the upper 95% confidence bound is less than 0% Difference [95% CI] TRI (N=1212) TFI (N=527) Difference [95% CI] TFI-TRI P-value (superiority) 99.9%99.0% -0.9% [-1.4%; -0.4%] <0.001 TRI is better TFI is better -3% 0% 3% Major bleeding complication-free rate at 7 days (major 2 nd endpoint) (After IPW adjustment)

25. Limitation Since randomization between TRI and TFI was made before assessing the feasibility of CABG or medical therapy, there might be some bias favoring for TFI.

26. Conclusion In real world PCI situation with ad-hoc PCI strategy, TRI is as effective as TFI in terms of 12 months’ MACCE, and TRI brings less incidence of bleeding complications at 1 week after PCI.