1. Bernardo Cortese, MD Ospedale della Misericordia Grosseto Italy
PROlonged Bivalirudin Infusion Versus Intraprocedural only RandomIzed study. The PROBI VIRI study.
Bernardo Cortese, MD
Ospedale della Misericordia
Grosseto Italy

2. Disclosures
Consultant (TMC, 2008).

3. BACKGROUND
Why do we use Bivalirudin? Short and long term follow up data from recent RCT.

4. Acuity trial HD White et Al., JACC 52;807
GW Stone et Al., NEJM 2006;355:2203

5. Horizons-AMI trial 3.1% 30 day Death (%) 2.1% P=0.048 HR [95%CI] =
Heparin + GPIIb/IIIa inhibitor (n=1802)
Bivalirudin monotherapy (n=1800)
3.1%
30 day Death (%)
2.1%
HR [95%CI] =
0.66 [0.44, 1.00]
P=0.048
Time in Days
GW Stone, oral communication, TCT ‘07

7. Bivalirudin’s shadows – I The Albion study

8. Clopidogrel pretreatment in Acuity (composite ischemia)
GW Stone et Al., NEJM 2006;355:2203

9. Bivalirudin’s shadows – II Isar React-3 trial
A Kastrati et Al., NEJM 2008;359:688

10. Bivalirudin’s shadows – III Horizons-AMI trial
GW Stone et Al., NEJM 2008;358:2218

11. Hypothesis: a prolonged infusion of bivalirudin after PCI would overcome these flaws??

12. “Antithrombotic protection”
Prolonged B
GPI
-Plt activation
-Distal embolization
-Small vess closure
-Stent thrombosis
B stop end of PCI
PCI
4 hrs
12 hrs
24 hrs
end of PCI
TIME

13. PROBI VIRI study- design
178 pts with SA or UA, complex PCI
Cath lab Biv bolus and infusion (1.75 mg/Kg/h)
Randomization (post angio)
Stop infusion (n=90)
4-hrs infusion at 0.25 mg/Kg/h (n=88)
Primary endpoint

14. Inclusion/Exclusion criteria
Stable or unstable angina and at least one of the following:
at least one B2/C lesion (ACC/AHA classification) or
planned MV PCI
any elevation of pre-procedural CK-MB or Tn,
creatinine clearance <30 ml/min,
previous use of heparin (2 hrs) or GPI,
INR>1.5

15. Study endpoints
Primary: incidence of procedural-related MI (CK-MB ≥ 3 ULN).
Secondary: in-hospital bleedings;
30-days and 6 months MACEs.

16. Statistical Methodology
randomization after angiography;
analysis by intention-to-treat;
superiority for P.E.
non-inferiority for S.E.
power analysis: to reduce post PCI MI incidence from 12% (control group) to 6% (prol biv group), a sample size of 160 pts would provide study 80% power to meet P.E.. Planned population: 175 pts.

17. Cr Clear <50 ml/min/m2, %
CONTROL
GROUP
(n=90)
PROL BIV
(n=88)
p value
Age, mean (SD), y
67,9 (±9,5)
66,7 (±9,8)
0.5
Males, % 80
80,7
0.9
Diabetes, %
27,7
29,5
Cr Clear <50 ml/min/m2, %
8,9
8,0
0.82
Unstable Angina, %
44,4
40,9
0.67
Aspirin use, before PCI, %
93.3
97.7 1
Correct clop. loading dose, %
86,7
86,4
0.7

18. Complex cor. lesions, B2/C type, %
CONTROL
GROUP
(n=90)
PROL
BIV (n=88)
p value
Complex cor. lesions, B2/C type, %
77,1
83,3
0.44
Direct stenting, %
77,8
73,9
0.5
Mean stent length (SD), mm
33,5 (±18)
32,2 (±18)
0.71
Radial access site, %
82,9
86,6
0.67
≥2 vessel PCI, %
28,3
33,3
0.79
Drug eluting stent use, %
44,4
54,6
0.4
In-cath lab GPI use, %
5,5
3,4
0.78
Procedural success, %
98,9
0.98

19. Results- P.E.
16,7%
p=0.041
6,8%

20. 30-days MACE, % Death, % Q-wave MI, % TVR, % 6-months MACE, %
CONTROL
GROUP
(n=90)
PROL BIV
(n=88)
p value
30-days MACE, %
3,3
1,1
0.43
Death, %
0.37
Q-wave MI, %
2,2
0.7
TVR, %
6-months MACE, %
16,7
10,2
0.18
4,4
3,4
0.76
12,2
8,0
0.33
Stent thrombosis, % 1

21. In-hospital Major Bleedings, %
CONTROL
GROUP
(n=90)
PROL BIV
(n=88)
p value
86,6% radial
access!
In-hospital Major Bleedings, %
1,1
0.87
In-hospital Minor Bleedings, %
3,3
3,4
0.96

22. Limitations of the study
post PCI bivalirudin infusion rate.
the last word about safety (radial access)?

23. CK MB increase after PCI
IS. REACT 3
ARMYDA 2
Briguori et Al.
(EHJ 04;25:1822)
Periproc MI
5.4%
15%
(>2 ULN)
16.4%
Any CK MB incr. above ULN
n.a.
26%
Preproc. CK MB increase 0%
Correct clop loading
100%
Complex lesions (B2/C)
67.5%
81%
64%
Stent length, mm
22.8 (±11)
20.8 (±10)
21 (±10)
MV PCI 9%
10%
PROBI VIRI
(stop Biv arm)
16.7%
28.9% 0%
86.7%
77.1%
33,5 (±18)
28.3%

24. Conclusions
In a complex PCI setting, bivalirudin prolonged infusion after PCI seems a promising choice to reduce
myocardial injury.
Urgent or Emergent PCI

25. Bivalirudin’s “Appendix”