Gert Richardt, MD, PhD Herzzentrum Segeberger Kliniken Bad Segeberg, Germany

1. ROTAXUSA Prospective, Randomized Trial of High-Speed Rotational Atherectomy Prior to Paclitaxel-Eluting Stent Implantation in Complex Calcified Coronary Lesions Gert Richardt, MD, PhD Herzzentrum Segeberger Kliniken Bad Segeberg, Germany

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 Boston Scientific Boston Scientific, Cordis J&J, Abbott Vascular, Medtronic None None None None 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 Relationship Company

3. Background (I) DES have shown favourable results when implanted in complex lesions and patients. Calcified coronary lesions can pose special problems, and may prevent stent delivery or expansion and increase the likelihood of stent thrombosis and/or restenosis. Calcified lesions may form a particular threat to DES, as damage to the polymer/drug coating and inadequate diffusion of the drug may decrease DES effectiveness.

4. Background (II) • Rotational atherectomy can effectively modify calcified plaques and facilitate stent delivery and expansion. • However, rotablation causes additional vessel injury with increased neointimal formation when used as a stand-alone therapy or combined with bare-metal stents. • Elective rotablation followed by DES implantation can be a rational complementary concept in complex calcified lesions, but this is not supported by randomized controlled studies.

5. Objective of the ROTAXUS trial .. to evaluate whether routine rotablation prior to PES implantation is more effective than the standard of care (stenting without rotablation) in the setting of complex calcified coronary artery disease.

6. ROTAXUS: Study Details • Design • Prospective, randomized, active-controlled clinical trial • Participating Centers • Heart Center, Segeberger Kliniken, Bad Segeberg, Germany • Heart Center Bad Krozingen, Bad Krozingen, Germany • University Hospital Hamburg-Eppendorf, Hamburg, Germany • Study Chair • Gert Richardt • Heart Center • Bad Segeberg, Germany • Principal Investigators • Mohamed Abdel-Wahab • Ahmed A. Khattab • Independent Data Safety and Monitoring Board • Independent QCA Core Lab (ISAR Research Center, Munich, Germany) • Independent Statistical Core Lab (Derek Robinson, Sussex, UK)

7. Inclusion Criteria • Clinical inclusion criteria • Age above 18 years • Angina and/or reproducible ischemia • Informed written consent • Angiographic inclusion criteria • First degree criteria (all) • De-novo lesion in a native coronary artery • Moderate to severe calcification • Second degree criteria (at least one) • Ostial location • Bifurcational lesion • Long lesion (≥ 15mm)

8. Exclusion Criteria • Clinical exclusion criteria • Myocardial infarction within 4 weeks • Left ventricular ejection fraction < 30% • Limited long term prognosis • Angiographic exclusion criteria • Unprotected left main lesions • Coronary artery bypass graft stenoses • In-stent restenoses • Chronic total occlusions • Target vessel thrombus • Target vessel dissection

9. Endpoints • Primary endpoint • In-stent late lumen loss at 9 months • Secondary endpoints • Major adverse cardiac events (MACE) • Definite stent thrombosis • In-segment late lumen loss • In-segment binary restenosis • Angiographic success • Strategy success (angiogr. success without crossover or stent loss) • Procedural duration • Contrast amount

10. Sample Size Calculation • Hypothesis • Rotablation prior to paclitaxel-eluting stent treatment will be superior to stenting without rotablation in reducing the late lumen loss at 9 months • Assumption • Late loss (primary endpoint) will be reduced from 0.5 ± 0.5 mm in the control group to 0.3 mm in the rotablation group • Power of 80% • One-sided alpha-level of 0.05 • Random sequence 1:1 • Needed total number of patients/lesions: 198 • Analysis by intention-to-treat

11. ROTAXUS 240 patients enrolled between August 2006 and March 2010 at 3 clinical sites in Germany 1:1 randomization Rota + PES (N=120) PTCA + PES (N=120) 240 patients analyzed with complete in-hospital follow-up • 2 patients died in-hospital • 6 patients withdrew consent • 5 patients lost at follow-up Clinical follow-up at 9 months in 96.2% (N=227) Angiographic follow-up at 9 months in 80.5% (N=190)

12. Baseline Characteristics (I)

13. Baseline Characteristics (II)

14. Angiographic Characteristics

15. Procedural Characteristics

16. Procedural Outcome (I)

17. Procedural Outcome (II) p = 1.0 p = 0.03 p = 0.02 p = 0.08 * Defined as <20% residual stenosis + TIMI 3 flow ** Defined as angiographic success with no crossover or stent loss

18. In-Hospital Outcome p = 0.17 * Defined as death, MI and TVR

19. QCA data: Index procedure

20. Primary Endpoint In-Stent Late Lumen Loss at 9 Months

21. Primary Endpoint p = 0.01 In-Stent Late Lumen Loss at 9 Months

22. QCA data: 9-month reangiography

23. Events at Follow-Up p = 0.46 p = 0.73 p = 0.84 p = 0.79 p = 0.78 p = 1.0 * Defined as death, MI and TVR

24. Summary (I) • Rotablation + PES implantation was not superior to balloon dilatation + PES implantation in reducing the primary endpoint of late lumen loss at 9 months in patients with complex calcified coronary artery disease. • Rotablation (probably due to additional vessel trauma) rather decreased the efficacy of PES in reducing neointimal growth.

25. Summary (II) • The superior acute gain obtained by rotablation was counterbalanced by an increased late loss resulting in a neutral effect on restenosis. • Rotablation remains an important bail-out device for uncrossable or undilatable coronary lesions and can improve overall success of DES implantation.

26. Thank You ROTAXUSHeart Center, Bad Segeberg, Germany