Safety, efficiency and cost effectiveness of Bivalirudin: A systematic review

Table 1 Dose information

Dose	0.75 mg/kg IV bolus then 1.75 mg/kg per hour if no prior antithrombotic therapy is administered For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV bolus, then 1.75 mg/kg per hour IV infusion
Half life	Healthy patients: 25 min. The half-life is Increased in patients with CKD, and is estimated to 3.5 h in dialysis-dependent patients
Mechanism of action	Reversible direct thrombin inhibitor. Thus, inhibits thrombin by directly binding to it
Theoretical advantages over heparin-	Directly inhibits thrombin
	Binds to clot-bound thrombin also
	Lab monitoring of efficacy is not required
	Does not cause HIT
	Short half life
	Almost nil thrombin induced platelet aggregation
Antidote and toxicity	No known antidote
	Should be discontinued 3 h before CABG
	In cases of toxicity, hemodialysis should be considered
CKD	Dose is reduced in patients with renal failure
Recommendations from the American College of Cardiology/American Heart Association and European Society of Cardiology for the use of bivalirudin in patients undergoing PCI	Class of recommendation - I, level of Evidence-B
	For patients undergoing PCI: Bivalirudin is useful as an anticoagulant with or without prior treatment with UFH
	Class of recommendation - I, level of Evidence-C
	With HIT: It is recommended that bivalirudin or argatroban be used to replace UFH
	Class of recommendation - I, level of Evidence-B
	Either discontinue bivalirudin or continue at 0.25 mg/kg per hour for up to 72 h at the physician’s discretion if given before diagnostic angiography and no PCI or CABG

PCI: Percutaneous coronary intervention; CKD: Chronic kidney disease; HIT: Heparin-induced thrombocytopenia; UFH: Unfractionated heparin.

Table 2 Major studies comparing bivalirudin and heparin

Trial name	Type of trial	Number of patients	Bleeding risk	Thrombosis risk	Mortality benefit	Comments
REPLACE-2	Randomized, double blind	6010	Favors bivalirudin	Bivalirudin noninferior	Bivalirudin noninferior
ACUITY	Randomized, open-label	13819	Favors bivalirudin	Comparable	Comparable
ARMYDA-7 BIVALVE	Randomized, open-label	401	Favors bivalirudin	Comparable	Comparable	Primarily decrease in access site bleeding in bivalirudin group
HORIZONS-AMI	Randomized, open-label, multicenter	3602	Favors bivalirudin	Comparable	Favors bivalirudin	Heparin group was given glycoprotein IIb/IIIa inhibitors
NAPLES	Randomized, open-label	355	Favors bivalirudin	Comparable	No deaths in study period	All patients with diabetes mellitus. Heparin group was given tirofiban
ISAR-REACT 4	Randomized, double-blind	1721	Favors bivalirudin	Comparable	Comparable	Heparin group was given abciximab
NAPLES III	Randomized, double-blind	837	Comparable	Not studied	Not studied	Femoral approach access in PCI
EUROMAX	Randomized, open-label	2218	Favors bivalirudin	Favors heparin	Comparable	GP IIb/IIIa inhibitor was optional in heparin group
HEAT-PPCI	Randomized, open-label	1829	Comparable	Favors heparin	Favors heparin	Use of GP IIb/IIIa was option in both groups
BRIGHT	Randomized, open-label	2194	Favors bivalirudin	Comparable	Comparable
MATRIX	Randomized, open-label	7213	Favors bivalirudin	Favors heparin	Favors bivalirudin	Post-PCI infusion of bivalirudin didn’t affect the outcome

PCI: Percutaneous coronary intervention.