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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. There was no commercial support for this study.

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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