ROTAXUSA Prospective, Randomized Trial of

High-Speed Rotational Atherectomy Prior to Paclitaxel-Eluting Stent Implantation in Complex Calcified Coronary Lesions

Gert Richardt, MD, PhDHerzzentrum

Segeberger KlinikenBad Segeberg, Germany

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 Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

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.

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.

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.

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)

Inclusion Criteria• Clinical inclusion criteria

1. Age above 18 years2. Angina and/or reproducible ischemia 3. Informed written consent

• Angiographic inclusion criteria First degree criteria (all)

1. De-novo lesion in a native coronary artery2. Moderate to severe calcification

Second degree criteria (at least one)1. Ostial location

2. Bifurcational lesion3. Long lesion (≥ 15mm)

Exclusion Criteria

• Clinical exclusion criteria1. Myocardial infarction within 4 weeks

2. Left ventricular ejection fraction < 30%

3. Limited long term prognosis

• Angiographic exclusion criteria1. Unprotected left main lesions

2. Coronary artery bypass graft stenoses

3. In-stent restenoses

4. Chronic total occlusions

5. Target vessel thrombus

6. Target vessel dissection

Endpoints

• Primary endpointIn-stent late lumen loss at 9 months

• Secondary endpoints1. Major adverse cardiac events (MACE)

2. Definite stent thrombosis

3. In-segment late lumen loss

4. In-segment binary restenosis

5. Angiographic success6. Strategy success (angiogr. success without crossover or stent loss)

7. Procedural duration

8. Contrast amount

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

ROTAXUS240 patients enrolled between August 2006 and March 2010 at 3

clinical sites in Germany

240 patients analyzed with complete in-hospital follow-up

Angiographic follow-up at 9 months in 80.5% (N=190)

Clinical follow-up at 9 months in 96.2% (N=227)

1:1 randomization

PTCA + PES(N=120)

Rota + PES(N=120)

- 2 patients died in-hospital- 6 patients withdrew consent- 5 patients lost at follow-up

Baseline Characteristics (I)

Rota + PES n = 120

PTCA + PES

n = 120

P Value

Age (years) 70.5±8.2 71.8±7.2 0.20Males 86 (72.3%) 96 (81.7%) 0.13BMI (kg/m2) 27.9±4.3 27.8±4.0 0.68Diabetes mellitus 33 (27.7%) 32 (26.8%) 0.88Hypertension 106 (89.1%) 95 (79.8%) 0.05Dyslipidemia 91 (76.5%) 87 (73.1%) 0.55Current smokers 24 (20.2%) 16 (13.5%) 0.17Family history of CAD 39 (32.8%) 44 (37.0%) 0.50Chronic renal failure 5 (4.2%) 8 (6.7%) 0.40Previous MI 38 (31.9%) 29 (24.4%) 0.20Previous PCI 44 (37.0%) 39 (32.8%) 0.50Previous CABG 9 (7.6%) 15 (12.6%) 0.20

Baseline Characteristics (II)

Rota + PES n = 120

PTCA + PES

n = 120

P Value

Unstable angina 17 (14.3%) 16 (13.4%) 0.85Left main disease 11 (9.2%) 8 (6.7%) 0.47Multivessel disease 88 (74.0%) 88 (74.0%) 1.0LV ejection fraction (%) 55.5±10.6 53.0±11.5 0.10Ad-hoc PCI 11 (9.3%) 9 (7.6%) 0.64Multilesion PCI 23 (19.3%) 32 (27.1%) 0.16Unfractionated heparin 49 (41.2%) 70 (50.4%) 0.15Bivalirudin 70 (58.8%) 59 (49.6%) 0.15GP IIb/IIIa antagonists 4 (3.4%) 0 0.12

Angiographic Characteristics

Rota + PES n = 146

PTCA + PES

n = 176

P Value

Location 0.06 Left main (protected) 3 (2.1%) 2 (1.1%) Left anterior descending 101 (69.2%) 111 (63.1%) Left circumflex 7 (4.8%) 22 (12.5%) Right coronary artery 35 (24.0%) 41 (23.3%)Reference vessel diameter (mm) 3.1±0.4 3.1±0.3 0.54Lesion length (mm) 20.6±9.3 18.5±9.2 0.04Diameter stenosis %) 81.5±10.2 80.0±10.8 0.23Ostial location 27 (18.5%) 31 (17.6%) 0.84Bifurcation 72 (49.3%) 82 (46.6%) 0.63Moderate/severe tortuosity 67 (46.2%) 83 (47.2%) 0.82Severe calcification 65 (44.5%) 86 (49.1%) 0.38B2/C lesion 137 (93.8%) 152 (86.3%) 0.03

Procedural Characteristics

Rota + PES n = 146

PTCA + PES

n = 176

P Value

7 Fr guiding catheter 122 (83.6%) 50 (28.4%) <0.001Balloon predilatation 130 (89.0%) 160 (90.9%) 0.58Max. predil. balloon size (mm) 2.5±0.3 2.6±0.4 0.37Max. predil. balloon pressure (atm) 13.6±5.1 15.8±4.9 0.04Starting burr size (mm) 1.5±0.2 -- --Max. burr size (mm) 1.5±0.2 -- --Use of > 1 burr 8 (5.5%) -- --Rotational speed (RPM) 165,947±8,919 -- --No. of stents / lesion 1.3±0.6 1.3±0.6 0.25Total stent length / lesion (mm) 27.7±12.2 25.2±11.5 0.06Balloon postdilatation 92 (63.0%) 116 (65.9%) 0.86Max. postdil. balloon size (mm) 3.3±0.5 3.3±0.4 0.88Max. postdil. balloon pressure (atm) 21.7±5.8 21.5±5.8 0.76

Procedural Outcome (I)

Rota + PES n = 120

PTCA + PES

n = 120

P Value

Procedural duration (min) 66.4±44.5 57.4±34.5 0.05Fluoroscorpy time (min) 22.8±21.9 18.1±16.7 0.04Contrast amount (ml) 201.0±113.6 181.8±93.6 0.11Dissections 4 (3.3%) 4 (3.3%) 1.0Perforations 2 (1.7%) 1 (0.8%) 0.56No/slow flow 0 1 (0.8%) 0.32

96.7%

0 4.2%

92.5%96.7%

2.5%12.3%

83.3%

0%

20%

40%

60%

80%

100%

Angiographicsuccess*

Stent loss Crossover Strategysuccess**

Rota+PES PTCA+PES

Procedural Outcome (II)

p = 0.03

p = 0.08

p = 1.0

* Defined as <20% residual stenosis + TIMI 3 flow** Defined as angiographic success with no crossover or stent loss

p = 0.02

5.9%

0

4.2%

0.8%0.8%1.7%1.7% 1.7%

0

4.2%

00.8%

3.4%

00%

2%

4%

6%

8%

10%

Death MI TV Re-PCI CABG MACE* ST Accesssite

compl.

Rota+PES PTCA+PES

In-Hospital Outcome

p = 0.17

* Defined as death, MI and TVR

QCA data: Index procedureRota + PES

n = 123

PTCA + PES

n = 132

P Value

Before procedure Lesion length (mm) 19.56±9.64 18.63±9.70 0.44 Refernce vessel diameter (mm) 2.67±0.41 2.77±0.37 0.04 Minimal lumen diameter (mm) 1.01±0.36 1.10±0.39 0.05 Diameter stenosis (%) 62.05±11.92 60.18±12.74 0.17

Immediately after procedure Minimal lumen diameter (mm) In-stent 2.58±0.37 2.56±0.40 0.61 In-segment 2.27±0.50 2.27±0.49 0.98 Diameter stenosis (%) In-stent 10.43±5.25 11.82±5.21 0.03 In-segment 17.68±8.98 19.38±16.67 0.18 Acute gain (mm) In-stent 1.57±0.43 1.46±0.46 0.03 In-segment 1.26±0.54 1.17±0.53 0.18

Primary Endpoint

0.44 mm

0.31 mm

0,0

0,1

0,2

0,3

0,4

0,5

Rota+PES PTCA+PES

In-Stent Late Lumen Loss at 9 Months

Primary Endpoint

0.44 mm

0.31 mm

0,0

0,1

0,2

0,3

0,4

0,5

Rota+PES PTCA+PES

p = 0.01

In-Stent Late Lumen Loss at 9 Months

QCA data: 9-month reangiography

Rota + PES n = 123

PTCA + PES

n = 132

P Value

Minimal lumen diameter (mm) In-stent 2.14±0.63 2.25±0.62 0.15

In-segment 1.91±0.57 2.02±0.65 0.16

Diameter stenosis (%) In-stent 22.01±19.92 19.86±19.64 0.26

In-segment 27.92±18.97 26.99±1.73 0.44

Late lumen loss (mm) In-stent 0.44±0.58 0.31±0.52 0.01

In-segment 0.36±0.57 0.25±0.57 0.04

Binary restenosis (%) In-stent 14 (11.4%) 14 (10.6%) 0.84

In-segment 15 (12.2%) 17 (12.9%) 0.87

0.8%

24.2%

11.7%16.7%

6.7%5.0%0

28.3%

12.5%18.3%

5.8%5.8%

0%

10%

20%

30%

40%

50%

Death MI TVR TLR MACE* Definite ST

Rota+PES PTCA+PES

Events at Follow-Up

p = 1.0

* Defined as death, MI and TVR

p = 0.78p = 0.79

p = 0.73p = 0.84

p = 0.46

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.

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.

Thank You

ROTAXUS Heart Center, Bad Segeberg, Germany