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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Elevated Plasma Fibrinogen Level Predicts Suboptimal Response to Therapy With Both Single- and Double-Bolus Eptifibatide During Percutaneous Coronary Intervention

Division of Cardiology, University of California at San Diego, San Diego, California.

Manuscript received March 7, 2006; revised manuscript received February 6, 2007, accepted March 6, 2007.

^_* Reprint requests and correspondence: Dr. Ehtisham Mahmud, Cardiovascular Catheterization Laboratories, UCSD Medical Center, 200 West Arbor Drive, San Diego, California 92103-8784. (Email: emahmud{at}ucsd.edu).

Objectives: This study sought to determine the factors associated with suboptimal platelet inhibition (PI) with single- and double-bolus eptifibatide during percutaneous coronary intervention (PCI).

Background: Although PI 95% measured 10 min after glycoprotein IIb/IIIa inhibitor therapy is associated with improved outcomes following PCI, this level of PI often is not achieved.

Methods: We prospectively studied 150 patients undergoing PCI with single-bolus eptifibatide (180 µg/kg) (n = 100) and double-bolus eptifibatide (180 µg/kg administered 10 min apart) (n = 50) followed by standard infusion (2 µg/kg/min). Measuring platelet aggregation at baseline and at 10 min and 30 to 45 min after eptifibatide bolus, patients were classified as optimal responders (OPT) (95% PI) or suboptimal responders (sub-OPT) (<95% PI) based on 10-min PI after final bolus.

Results: Suboptimal PI was achieved in 61% of patients with single-bolus eptifibatide and in 36% with double-bolus eptifibatide. In the single-bolus group, sub-OPT had higher fibrinogen levels (324 ± 85 mg/dl vs. 259 ± 49 mg/dl, p = 0.0002), platelet counts (221 ± 70 vs. 186 ± 47, p = 0.008), and white blood cell counts (7.7 ± 2.3 vs. 6.6 ± 1.9, p = 0.02). In the double-bolus group, sub-OPT also had higher fibrinogen levels (324 ± 68 mg/dl vs. 278 ± 53 mg/dl, p = 0.01) and were more likely to be smokers (38.9% vs. 9.4%, p = 0.01). Multivariable analysis showed that fibrinogen level was the only independent predictor of suboptimal PI, with fibrinogen cutoffs at 375 and 325 mg/dl predicting suboptimal PI (single-bolus: 100% and 90.0%, respectively; double-bolus: 100% and 60%, respectively) with both doses.

Conclusions: During PCI, both single- and double-bolus eptifibatide provide suboptimal PI in a substantial proportion of patients. A fibrinogen level >375 mg/dl is a strong predictor of suboptimal PI.

Abbreviations and Acronyms   CK = creatine kinase   CRP = C-reactive protein   GP = glycoprotein   MACE = major adverse cardiac events   OPT = optimal responders   PCI = percutaneous coronary intervention   PI = platelet inhibition   ROC = receiver-operator characteristic   sub-OPT = suboptimal responders

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