Effect of body mass index on Argatroban therapy during percutaneous coronary intervention

Abstract

Obesity is common in patients undergoing percutaneous coronary intervention (PCI). Argatroban, a direct thrombin inhibitor, is used during PCI in patients with or at risk of heparin-induced thrombocytopenia (HIT) and also has been evaluated in conjunction with glycoprotein IIb/IIIa inhibition in nonHIT patients. We investigated the effect of body mass index (BMI), and specifically obesity (BMI>30 kg/m2), on argatroban therapy during PCI. From previously reported studies of argatroban therapy during PCI in patients with or at risk of HIT (ie, HIT group) or in conjunction with glycoprotein IIb/IIIa inhibition (ie, nonHIT group), we identified patients with sufficient data to determine BMI. After an initial bolus of 350 microg/kg (HIT group) or 300 or 250 microg/kg (nonHIT group), patients received continuous argatroban 25-30 microg/kg/min (adjusted to achieve ACTs of 300-450 s, HIT group) or 15 microg/kg/min (target ACTs of 275-325 s, nonHIT group) during PCI, with additional 150 microg/kg boluses allowed if needed. Regression analyses evaluated relationships between patient BMI and ACT response to initial bolus administration, mean infusion dose (HIT group only), and rate of ACT decline after PCI. Frequencies of additional bolus usage and clinical outcomes were compared between obese and nonobese patients. Our analysis population included 225 patients (85 obese) in total: 73 in the HIT group and 152 in the nonHIT group (300 microg/kg bolus, n=101; 250 microg/kg bolus, n=51), with BMIs of 16.3-50.9 kg/m2. No association was detected between BMI and the first ACT after bolus administration (median ACTs of 361, 298, and 289 s, respectively, following 350, 300, and 250 microg/kg bolus), mean infusion dose (24.2+/-4.9 microg/kg/min overall in HIT group), or time to ACTs<or=160 s after argatroban cessation (median 4.4 h in HIT group and 1.7-2.1 h in nonHIT group). Fifteen (5 obese) patients in the HIT group and 36 (13 obese) in the nonHIT group required additional boluses, without differences by obesity versus nonobesity (P>or=0.35). Clinical outcomes did not differ (P>or=0.09) between obese and nonobese individuals: 4 (3 obese) patients in the HIT group and 4 (2 obese) in the nonHIT group had ischemic complications; 1 nonobese patient in the HIT group and 2 (1 obese) in the nonHIT group experienced major bleeding. These findings support the use of actual body weight-adjusted (and ACT-targeted) argatroban therapy during PCI and suggest that dose adjustment for obesity (BMI up to 50.9 kg/m2) is unnecessary.