Impact of renal function on argatroban therapy during percutaneous coronary intervention

Abstract

Argatroban, a hepatically metabolized direct thrombin inhibitor, is approved for anticoagulation in patients with or at risk of heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). We investigated the effect of renal function on argatroban therapy during PCI. From previous argatroban studies in PCI, we evaluated relationships between estimated creatinine clearance (CrCl) and activated clotting times (ACTs), dosage, and outcomes in 219 patients with or at risk of HIT (HIT group, n = 67) or administered glycoprotein IIb/IIIa inhibition (non-HIT group, n = 152). Patients received an argatroban bolus (350 mcg/kg, HIT group; 250 or 300 mcg/kg, non-HIT group) then 25-30 mcg/kg/min (adjusted to achieve ACTs 300-450 s, HIT group) or 15 mcg/kg/min (target ACTs 275-325 s, non-HIT group), with additional 150-mcg/kg boluses if needed. Of 219 patients, 55 (25%) had CrCl <or= 60 ml/min (8 with CrCl <or= 30 ml/min). Regression analyses detected no association between CrCl (range 7-231 ml/min) and initial ACT (by bolus) or mean infusion dose. Multi-bolus usage was similar in patients with, versus without, CrCl <or= 60 ml/min. In the non-HIT group, CrCl was associated (P = 0.01) with the time to ACT <or= 160 s after argatroban cessation (approximately 17 min slower per 30-ml/min CrCl decrease). Eight patients (none with CrCl <or= 60 ml/min) had ischemic complications. Three patients (1 with CrCl 40 ml/min) experienced major bleeding. Argatroban dose adjustment for renal function appears unnecessary during PCI. Renal dysfunction may be associated with slower (by minutes) ACT effect decay after argatroban cessation. Argatroban is well tolerated in PCI patients with renal impairment.

Heparin-Induced Thrombocytopenia in Cardiovascular Patients

“…75 Due to its metabolism by the liver, argatroban (initial or maintenance) dose adjustments for renal function are not needed during PCI. Hursting and Jang 97 reported in a retrospective analysis that ACT has no association to creatinine clearance with the use of argatroban during PCI for HIT patients.…”

“…95,96 For patients with renal insufficiency, argatroban shows reliable dose-related anticoagulation activity in both non-PCI and PCI-treated patients. 90,97 Argatroban, as well as other DTIs, increases the INR, especially when it is bridged to warfarin therapy. When warfarin is given concomitantly with argatroban, the prothrombin time is excessively prolonged, and an INR of 4.0 can be regarded as equivalent to an INR 2.0 to 3.0 on warfarin only.…”

Role of argatroban during neurointerventional procedures in patients with heparin induced thrombocytopenia

“…For HIT treatment, therapeutic levels of argatroban are achieved when the activated partial thromboplastin time is 1.5–3.0 times baseline 14. For PCI, therapeutic levels of argatroban are achieved when ACT is 300–450 s 14 16 17…”

Pharmacology of argatroban

“…In a retrospective Pharmacology of argatroban Drug Profile analysis of case records collected as part of prospective clinical studies of argatroban therapy in HIT patients, altered renal function did not significantly impact the aPTT response or the rates of thrombosis or bleeding associated with argatroban therapy [21]. A retrospective analysis of data obtained from prospective studies of argatroban therapy during percutaneous intervention indicated that renal dysfunction did not impact the initial activated clotting time (ACT) following bolus administration, the mean peri-procedural infusion dose or the need for multiple bolus doses [22]. However, there was the suggestion that the time required for the ACT to return to a level of 160 s or less was increased with renal dysfunction.…”