A randomised comparison of reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting stents in patients with diabetes mellitus: the RESERVOIR clinical trial

1. A randomised comparison of reservoir-based
polymer-free amphilimus-eluting stents versus
everolimus-eluting stents in patients with
diabetes mellitus: the RESERVOIR clinical trial
Rafael Romaguera, Luis Teruel, Joan A Gómez-Hospital, Josep Gomez-Lara,
Salvatore Brugaletta, Eduardo Pinar, Pilar Jiménez-Quevedo, Montserrat
Gracida, Gerard Roura, Jose L Ferreiro, Eduard Montanya, Antonio Fernandez-
Ortiz, Fernando Alfonso, Marco Valgimigli, Manel Sabate, Angel Cequier
Clinical trial info: NCT01710748

2. • Patients with DM remain at high risk for in-stent restenosis and
adverse cardiovascular events despite the use of DES.
• 2nd-gen DES provide superior safety and efficacy results as
compared with 1st-gen DES.
• EES is the DES with the most robust evidence of safety and
efficacy.
Background
81 µm Co Cr
Non-erodable flurocopolymer
Conformal configuration
Everolimus 100 μg/cm2
70-80 µm Co Cr
Polymer-free
Carbon coating
Sirolimus 90 μg/cm2
Amphiphilic carrier
EES AES
Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid

3. Methods
Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Primary endpoint: Neointimal volume obstruction by OCT
Secondary: Uncovered struts, LLL, TVR
Exclusion criteria
Life-style changes only
STEMI
Bifurcation>2.5mm
Left Main/ostial LAD
3V with CABG indication
GFR<30 ml/min
LVEF < 30%
Contraindication DAPT

4. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Results: Study flow-chart

5. Results: Baseline characteristics
Characteristic
AES
56 patients
EES
56 patients p value
Age 66.7 ± 9.8 67.2 ± 8.8 0.75
Hb1Ac 7.5 ±1.2 7.5 ± 1.2 0.80
LDL cholesterol 82.8 ± 39.2 80.7 ± 32.5 0.76
Creatinine 0.99 ± 0.26 0.95 ± 0.23 0.34
Diabetic nephropathy 9 (16.1) 13 (23.2) 0.34
Diabetes treatment
- Insulin 21 (37.5) 24 (42.9) 0.563
- Biguanides 48 (53.9) 41 (74.5) 0.14
Number of vessels diseased 1.61 ± 6.5 1.61 ± 7.3 1.0
Total stent length 21.5 ± 6.9 20.7 ± 7.6 0.53
Stent diameter 3.04 ± 0.35 2.93 ± 0.33 0.07
Number of stents per lesion 1.12 ± 0.33 1.05 ± 0.22 0.19
Angiographic success 58 (100) 58 (100) 1.0
Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid

6. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
AES
50 patients
/52 lesions
EES
49 patients
/50 lesions
p value
Before index procedure
RVD (mm) 2.69 ±0.54 2.55 ± 0.49 0.16
Diameter stenosis (% ± SD) 66.12 ± 14.88 64.72 ±12.28 0.61
After index procedure
RVD (mm) 2.70 ± 0.47 2.64 ±0.48 0.50
MLD (mm)
In-stent
In-segment
2.51 ± 0.37
2.15 ± 0.50
2.43 ± 0.36
2.06 ± 0.53
0.24
0.37
Acute gain (mm)
In-stent
In-segment
1.59 ± 0.40
1.22 ± 0.46
1.54 ± 0.43
1.17 ± 0.60
0.52
0.59
Results: Baseline characteristics (QCA)

7. Δ -10 -5 0 +5.3 +10
Superiority Non-inferiority Inferiority
Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Primary endpoint: Neointimal Volume Obstr.
-4.1 +2.6
p for non-inferiority = 0.0003 p for superiority = 0.22

8. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Secondary endpoints
0
0.5
1
1.5
2
2.5
3
3.5
Uncovered Uncovered &
malapposed
AES
EES
2.2
3.4
0.6
0.9
all p > 0.40

9. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Pre specified subgroup analysis

10. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Interaction between glycaemic control
and stent effect
dHb1
12,010,08,06,0
NVO(%)
,5000
,4000
,3000
,2000
,1000
,0000
Hb1Ac
7.3%
Cre8 better
p = 0.025

11. AES EES p value
MLD (mm)
In-stent
In-segment
2.38 ± 0.44
2.09 ± 0.45
2.19 ± 0.59
1.84 ± 0.61
0.07
0.02
Late lumen loss
0.14 ± 0.24 0.24 ± 0.57

12. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Secondary endpoints:
Clinical events at 12 months
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
1.8%
0.0% 0.0%
5.2% 5.2%
6.9%
10.7%
0.0%
1.8% 1.7%
8.6%
12.1%
12.1%
10.7%
AES EES

13. Hospital Clínico San Carlos
Madrid
Hospital Clínico San CarlosHospital Clínico San Carlos
Madrid
Conclusions
• First study to show non inferiority of a PF-DES compared to EES
in DM.
(Formulation of the antiproliferative drug with an amphiphilic
carrier results in non-inferior efficacy than the classic elution from
durable polymers for the coronary revascularization of patients
with DM)
• This trial suggests a high efficacy of AES in DM, but it must be
confirmed in a large RCT (warranted).