1. ClinicalTrials.gov Identifier NCT00262054
ISAR
REACT 3
ClinicalTrials.gov Identifier NCT
Bivalirudin Versus Unfractionated Heparin in Biomarker Negative Patients With Stable and Unstable Angina Undergoing PCI
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
LBCT
March 29, 08

2. ISAR
REACT 3
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.
LBCT
March 29, 08

3. ISAR
REACT 3
Aim
To compare bivalirudin alone to unfractionated heparin alone in biomarker negative pts undergoing PCI pretreated with clopidogrel 600 mg for >2 hours
Hypothesis
Bivalirudin is superior to UFH for biomarker negative patients undergoing PCI after optimal pretreatment with clopidogrel
LBCT
March 29, 08

4. ISAR
REACT 3
Exclusion Criteria
Acute coronary syndromes with positive biomarkers or ST-segment elevation on ECG
Cardiogenic shock
Active bleeding, bleeding diathesis
Impaired renal function (creatinine >3 mg/dl)
LBCT
March 29, 08

5. Primary (Quadruple) Endpoint at 30 Days
ISAR
REACT 3
Primary (Quadruple) Endpoint at 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 Hb>3 g/dL, or
Any decrease in Hb>4 g/dL, or
Transfusion of >2 units of packed red blood cells or whole blood
LBCT
March 29, 08

6. Secondary (Triple) Endpoint at 30 Days
ISAR
REACT 3
Secondary (Triple) Endpoint at 30 Days
Composite rate of:
Death
Myocardial infarction
Urgent target vessel revascularization
LBCT
March 29, 08

7. Study Population 2,289 Pts 2,281 Pts
ISAR
REACT 3
Study Population
Double-blind randomization; double-dummy administration
4,570 Patients (600 mg clopidogrel)
Bivalirudin
UFH
2,289 Pts
2,281 Pts
PCI
30-day Follow-up
LBCT
March 29, 08

8. Type of PCI Bivalirudin UFH ISAR REACT 3 6% BMS 7% DES 84% DES 82% 10%
PTCA
11%
LBCT
March 29, 08

9. Secondary (Triple) Endpoint Death, MI, UTVR
ISAR
REACT 3
Secondary (Triple) Endpoint Death, MI, UTVR
Cumulative incidence (%) 10 8
Bivalirudin 6
5.9%
5.0%
UFH 4
RR=1.16 [95% CI, ], P=0.23 2 5 10 15 20 25 30
Days after randomization
LBCT
March 29, 08

10. Bleeding Events ISAR REACT 3 Bivalirudin Incidence (%) UFH P=0.008
LBCT
March 29, 08

11. Primary (Quadruple) Endpoint Death, MI, UTVR, Major Bleeding
ISAR
REACT 3
Primary (Quadruple) Endpoint Death, MI, UTVR, Major Bleeding
Cumulative incidence (%) 10
UFH
8.7%
8.3% 8
Bivalirudin 6 4
RR=0.94 [95% CI, ], P=0.57 2 5 10 15 20 25 30
Days after randomization
LBCT
March 29, 08

12. ISAR
REACT 3
Conclusion
In biomarker negative patients with stable and unstable angina undergoing PCI pretreated with clopidogrel 600 mg for >2 hours, bivalirudin does not improve “net clinical benefit” – the quadruple endpoint – at 30 days compared to UFH, although it significantly reduces bleeding
LBCT
March 29, 08