LBCT

1
Bivalirudin Versus Unfractionated Heparin in
Biomarker Negative Patients With Stable and
Unstable Angina Undergoing PCI
ClinicalTrials.gov Identifier NCT00262054
ISAR-REACT 3
(Intracoronary Stenting and Antithrombotic
Regimen-Rapid Early Action for Coronary
Treatment 3)

• A. Kastrati, F.-J. Neumann, J. Mehilli,
  S. Schulz, G. Richardt, R. Iijima, R.A. Byrne,
  P.B. Berger, A. Schömig

2
Background

• Bivalirudin has not been compared with
  unfractionated heparin during PCI in the modern
  era, or in patients who have received optimal
  pretreatment with clopidogrel.

3

• Aim
• To compare bivalirudin alone to unfractionated
  heparin alone in biomarker negative pts
  undergoing PCI pretreated with clopidogrel 600 mg
  for gt2 hours
• Hypothesis
• Bivalirudin is superior to UFH for biomarker
  negative patients undergoing PCI after optimal
  pretreatment with clopidogrel

4
Exclusion Criteria

• Acute coronary syndromes with positive biomarkers
  or ST-segment elevation on ECG
• Cardiogenic shock
• Active bleeding, bleeding diathesis
• Impaired renal function (creatinine gt3 mg/dl)

5
Primary (Quadruple) Endpointat 30 Days

• Composite rate of
• Death
• Myocardial infarction (defined as CK-MB 2x
  upper limit normal)
• Urgent target vessel revascularization
• Major bleeding (according to the REPLACE-2
  criteria, JAMA '03)

• Intracranial, intraocular, or retroperitoneal
  bleeding, or
• Clinically overt bleeding resulting in a decrease
  in Hbgt3 g/dL, or
• Any decrease in Hbgt4 g/dL, or
• Transfusion of gt2 units of packed red blood cells
  or whole blood

6
Secondary (Triple) Endpointat 30 Days

• Composite rate of
• Death
• Myocardial infarction
• Urgent target vessel revascularization

7
Study Population
Double-blind randomization double-dummy
administration
4,570 Patients(600 mg clopidogrel)
UFH
Bivalirudin
2,289 Pts
2,281 Pts
PCI
30-day Follow-up
8
Type of PCI
Bivalirudin
UFH
BMS
6
7
DES 84
DES 82
PTCA
10
11
9
Secondary (Triple) EndpointDeath, MI, UTVR
Cumulative incidence ()
10
8
Bivalirudin
5.9
6
5.0
UFH
4
RR1.16 95 CI, 0.91-1.49, P0.23
2
0
0
5
10
15
20
25
30
Days after randomization
10
Bleeding Events
Bivalirudin
UFH
Incidence ()
P0.008
P0.0001
P0.15
11
Primary (Quadruple) EndpointDeath, MI, UTVR,
Major Bleeding
Cumulative incidence ()
10
UFH
8.7
8.3
8
Bivalirudin
6
4
RR0.94 95 CI, 0.77-1.15, P0.57
2
0
0
5
10
15
20
25
30
Days after randomization
12
Conclusion

• In biomarker negative patients with stable and
  unstable angina undergoing PCI pretreated with
  clopidogrel 600 mg for gt2 hours, bivalirudin
  does not improve net clinical benefit the
  quadruple endpoint at 30 days compared to UFH,
  although it significantly reduces bleeding