1. Treatment of Calcified Coronary Lesions: Insights from Randomized Trials
David J. Cohen, M.D., M.Sc.
Director of Cardiovascular Research
Saint Luke’s Mid America Heart Institute
Professor of Medicine, University of Missouri-Kansas City
CRT mins

2. Disclosures Grant Support/Drugs Grant Support/Devices
Daiichi-Sankyo - Merck
Astra-Zeneca
Grant Support/Devices
Edwards Lifesciences - Abbott Vascular
Medtronic - Boston Scientific
Biomet - CSI
Consulting/Advisory Boards
Medtronic - Astra-Zeneca
Edwards Lifesciences - Cardinal Health
DJC: 2/17

3. Calcified Lesions
Background
Calcified lesions are common among patients undergoing PCI prevalence ranges from 10-30% depending on the definition and patient population (ACS vs. chronic CAD)
PCI in pts with calcified lesions is associated with…
Reduced rates of procedural success
Worse long-term outcomes, mainly related to more frequent repeat revascularization (? ‘d mortality)
PCI in pts with calcified lesions is also associated with higher short- and long-term costs

4. Medicare Calcified Lesion Study
Patient population derived from Medicare data and includes all pts aged > 65 who underwent attempted PCI in
Patients with “severely calcified” lesions identified by specific ICD-9 code (414.4)
Propensity-matching (4:1) used to balance baseline characteristics
Calcified: 2,276
Non-Calcified: 9,104
Clinical outcomes (death, MI, repeat revasc, hospitalization) and costs assessed through 1-year f/u
Baron SJ, et al. CRT 2016

5. Clinical Outcomes at 1 year Count per 100 patients
Calcified
(n=2,276)
Non-Calcified
(n=9,104)
P value
Death
9.4
9.7
0.657
Myocardial Infarction
27.2
24.9
0.415
Repeat Revascularization PCI CABG
Repeat Hospitalization
Cardiovascular
Non-Cardiovascular
66.1
43.2
68.4
47.4
0.595
0.214
Outpatient Visit
827.9
829.4
0.939
Baron SJ, et al. CRT 2016

6. Medicare Costs Calcified Non-Calcified Difference (95% C.I.) P value
Index Hosp.
$25,236
$22,668
2568 (1881 to 3256)
< 0.001
Repeat CV Hosp.
With Revasc.
Without Revasc.
Total
$3,551
$6,211
$9,763
$2,577
$7,226
$9,803
974 (175 to 1774)
-1015 (-2520 to 490)
-40 (-1810 to 1729)
0.016
0.186
0.964
Non-CV Hosp.
$5,842
$5,291
893 (-1198 to 2301)
0.536
Outpatient Care
$13,737
$12,071
1666 (-681 to 4014)
0.164
Total 1-year Cost
$54,579
$49,833
4746 (790 to 8702)
0.018
* Propensity matched analysis
Baron SJ, et al. CRT 2016

7. Unresolved Question Does plaque modification/lesion preparation in patients with calcified lesions lead to improved long-term outcomes?

8. ROTAXUS Trial
240 patients undergoing PCI for moderate or severely calcified lesion
Moderate Ca++  radioopacity noted only during cardiac motion
Severe CA++  radioopacity noted without motion and including both sides of vessel
Randomized to rota/stenting vs. standard PTCA/stenting (TAXUS stent)
Rotablator performed with burr:artery ratio
Primary endpoint = angiographic late loss

9. Baseline Characteristics
ROTAXUS
Baseline Characteristics
RA + PES (n=120)
Std. PES (n=120)
Age
70.5
71.8
Male
72.3%
81.7%
Diabetes
27.7%
26.8%
Current smoker
20.2%
13.5%
Renal Failure
4.2%
6.7%
Prior CABG
7.6%
12.6%
Multilesion PCI
19.3%
27.1%
Presentation
Stable CAD
85.7%
86.4%
Unstable Angina
14.3%
13.6%
P= NS for all comparisons
Abdel-Wahab M, et al. JACC Intv 2013;6:10-19

10. Angiographic Characteristics
ROTAXUS
Angiographic Characteristics
RA + PES (n=146)
Std. PES (n=176)
Vessel Treated LM
2.1
1.1
LAD
69.2
63.1
LCx
4.8
12.5
RCA
24.0
23.3
Severe Calcification
44.5%
49.1%
Lesion Length
19.5 mm
18.0 mm
Ref Vessel Diameter
2.7 mm
2.8 mm
RA + PES (n=146)
Std. PES (n=176)
Vessel Treated LM
2.1
1.1
LAD
69.2
63.1
LCx
4.8
12.5
RCA
24.0
23.3
Severe Calcification
44.5%
49.1%
Lesion Length
19.5 mm
18.0 mm
Ref Vessel Diameter
2.7 mm
2.8 mm
Lesion based analysis
Abdel-Wahab M, et al. JACC Intv 2013;6:10-19

11. Procedural Outcomes ROTAXUS RA + PES Std. PES P-Value
Procedure duration
66.4 mins
57.4 mins
0.05
Crossover to alt. strategy
4.2%
12.5%
0.02
Stents per lesion
1.3 NS
Procedural Outcomes
Perforation
1.7%
0.8%
Stent Loss
0.0%
2.5%
0.08
Strategy Success
92.5%
83.3%
0.03
Angiographic Success
96.7%
* Strategy success = angiographic success without crossover or stent loss
Abdel-Wahab M, et al. JACC Intv 2013;6:10-19

12. Angiographic Outcomes
ROTAXUS
Angiographic Outcomes
RA + PES
Std. PES
P-Value
Post Procedure (in-stent)
Acute gain, mm
1.56 ± 0.43
1.44 ± 0.49
0.01
MLD, mm
2.57 ± 0.38
2.55 ± 0.45 NS
Diameter stenosis, %
10.8 ± 5.6
12.3 ± 7.9
0.04
9-Month Follow-up (in stent)
Late Loss, mm*
0.44 ± 0.58
0.31 ± 0.52
2.14 ± 0.63
2.25 ± 0.62
22.0 ± 19.9
19.9 ± 19.6
Binary Restenosis
11.4%
10.6%
RA + PES
Std. PES
P-Value
Post Procedure (in-stent)
Acute gain, mm
1.56 ± 0.43
1.44 ± 0.49
0.01
MLD, mm
2.57 ± 0.38
2.55 ± 0.45 NS
Diameter stenosis, %
10.8 ± 5.6
12.3 ± 7.9
0.04
9-Month Follow-up (in stent)
Late Loss, mm*
0.44 ± 0.58
0.31 ± 0.52
2.14 ± 0.63
2.25 ± 0.62
22.0 ± 19.9
19.9 ± 19.6
Binary Restenosis
11.4%
10.6%
Abdel-Wahab M, et al. JACC Intv 2013;6:10-19

13. 9-Month Clinical Outcomes
ROTAXUS
9-Month Clinical Outcomes
Rota/Stent
Std. Stent
P=NS for all comparisons
Death MI
TLR
TVR
Abdel-Wahab M, et al. JACC Intv 2013;6:10-19

14. Why Was ROTAXUS Negative?
Calcified Lesions
Why Was ROTAXUS Negative?
Inclusion of moderately calcified lesions?
Not enough ablation? (mean burr 1.5 mm)
Crossovers are refractory lesions the ones that really benefit?
Wrong endpoint? f/u MLD probably more appropriate as an angiographic surrogate
Underpowered for clinical endpoints
No true benefit?

15. Design Considerations for a Contemporary Trial
Calcified Lesions
Design Considerations for a Contemporary Trial
Parameter
Considerations
Patient population
Severe calcification vs. moderate/severe

16. Design Considerations for a Contemporary Trial
Calcified Lesions
Design Considerations for a Contemporary Trial
Parameter
Considerations
Patient population
Severe calcification vs. moderate/severe
Comparator strategy
PTCA/Stent or Rota/Stent

17. Design Considerations for a Contemporary Trial
Calcified Lesions
Design Considerations for a Contemporary Trial
Parameter
Considerations
Patient population
Severe calcification vs. moderate/severe
Comparator strategy
PTCA/Stent or Rota/Stent
Primary endpoint
Angiographic vs. Clinical

18. Design Considerations for a Contemporary Trial
Calcified Lesions
Design Considerations for a Contemporary Trial
Parameter
Considerations
Patient population
Severe calcification vs. moderate/severe
Comparator strategy
PTCA/Stent or Rota/Stent
Primary endpoint
Angiographic vs. Clinical
Crossover permitted
If not, may be challenging to enroll

19. Design Considerations for a Contemporary Trial
Calcified Lesions
Design Considerations for a Contemporary Trial
Parameter
Considerations
Patient population
Severe calcification vs. moderate/severe
Comparator strategy
PTCA/Stent or Rota/Stent
Primary endpoint
Angiographic vs. Clinical
Crossover permitted
If not, may be challenging to enroll
Stent type
2nd gen DES vs. BVS

20. Calcified Lesions
Summary/Conclusions
Ablative techniques are an important adjunct to standard PTCA/stenting for treatment of refractory lesions and heavily calcified lesions
Whether these approaches provide meaningful benefit compared with standard PTCA/stenting except for truly refractory lesions is unknown
High quality clinical trials (most likely with clinically relevant endpoints) will ultimately be necessary to make the case for routine use of orbital atherectomy (or any other ablative techniques) in contemporary practice