Bivalirudin

Bivalirudin

1. Bivalirudin Dr. Sayeedur Rahman Khan Rumi [email protected] MD (Cardiology) Final Part Student National Heart Foundation Hospital and Research

2. Bivalirudin Bivalirudin is a 20–amino acid polypeptide. A synthetic version of hirudin . In contrast to hirudin , bivalirudin is not immunogenic.

3. Pharmacokinetics Bivalirudin is easy to use, has linear kinetics. It is not protein-bound so few drug interactions. Mechanism of action: It inhibits both soluble and clot-bound thrombin and blocks thrombin mediated platelet activation and aggregation. Half-life: 25 minutes.

4. Pharmacokinetics Elimination: Predominantly achieved by proteolytic cleavage. To a lesser extent, by renal excretion. Clearance is reduced by only approximately 20% in moderate and severe renal impairment. This may be particularly advantageous in CKD as the risk of bleeding is approximately doubled. Coagulation tests (APTT and ACT) correlate well with plasma concentrations.

5. Dose I/V bolus 0.75 mg/kg prior to the intervention Followed by an infusion of 1.75 mg/kg/hour for the duration of the procedure. Chronic kidney disease: The ESC recommends an infusion rate of 1.75 mg/kg/hour for moderate renal impairment ( CrCl , 30-59 mL/min) If the clearance is less than 30 mL/min, reduce to 1mg/kg/hour

6. ACS with planned PCI In ACS with planned PCI, the ACUITY trial showed that bivalirudin alone gave similar outcome rates to heparin plus GpIIb / IIIa inhibition with less bleeding.

7. Urgent PCI in high-risk non–STE ACS For urgent PCI in non-STE ACS, bivalirudin is a cost-effective alternative to UFH plus GpIIb / IIIa blockade and gives less bleeding. In ACUITY trial, GpIIb / IIIa antagonists added to bivalirudin increased bleeding but gave no outcome benefit. Despite absence of firm data, the AHA-ACC guidelines suggest that bivalirudin should be combined with clopidogrel to optimize outcomes. Given the adverse relationship of bleeding,to long-term mortality, bivalirudin is a reasonable alternative to UFH or LMWH with added GpIIb / IIIa antagonists. The current preferred approach for non-STE ACS is to use bivalirudin in patients at high risk of bleeding

8. Primary PCI in STEMI For primary PCI in STEMI, in the HORIZONS study on 3602 patients bivalirudin reduced major bleeding by 40% and also reduced 30-day mortality as compared with UFH and a GpIIb / IIIa receptor antagonist. Thus this agent is an attractive antithrombotic option for primary PCI compared with UFH plus GpIIb / IIIa antagonists and can be given to all those with ACS. Long-term final 3-year results of the primary PCI trial HORIZONS-AMI show continued mortality benefit of bivalirudin and also suggest possible late benefits on stent thrombosis and repeat MI.

9. Less bleeding vs. heparin At similar ACTs in patients undergoing PCI, bivalirudin had consistently less bleeding than did heparin or heparin plus a Gp inhibitor

10. HEPARIN & GPI versus BIVALIRUDIN Effects of bivalirudin in decreasing deaths in acute myocardial infarction

11. Take home message Bivalirudin is a valuable agent to replace heparin or UFH during PCI. An important outcome study shows mortality reduction versus heparin and a GpIIb / IIIa antagonist when used for acute STEMI. It causes relatively less bleeding than does heparin in unselected patients undergoing PCI. Bivalirudin is also licensed for patients with or at risk of HIT or HITTS who are undergoing PCI.

12. Thank you