Glycoprotein IIb/IIIa inhibitors in patients with renal insufficiency undergoing percutaneous coronary intervention

Glycoprotein IIb/IIIa receptor antagonists (GPRAs) are agents that block the final common pathway in platelet aggregation by inhibiting the binding of fibrinogen to the GPR on the surface of activated platelets, which then decreases crosslinking of platelets and thus platelet aggregation. Treatment guidelines recommend that patients undergoing percutaneous coronary intervention (PCI) be treated with a regimen of antithrombotic therapy that includes a GPRA to decrease the risk of ischemic events. Three GPRAs are currently available for use in the United States: abciximab (ReoPro), tirofiban (Aggrastat), and eptifibatide (Integrilin). Tirofiban and eptifibatide are renally cleared and thus must have dosage adjustment if used in patients with renal insufficiency (RI). Abciximab is not renally eliminated and does not require dosage adjustment in RI. Bleeding has been associated with worse outcomes after PCI and is the major risk associated with the use of GPRAs. Approximately 30% of PCI patients have RI, and RI increases the risk of bleeding. Unfortunately, clinical trials of GPRAs in PCI have excluded patients with moderate to severe RI. Several subgroup analyses and single center cohort analyses have analyzed the safety of GPRAs in patients with RI. These analyses have confirmed that bleeding is increased in patients with RI and in patients receiving GPRAs; however, the risk does not seem to be magnified by the combination of RI and GPRA therapy. These results are limited by the small study sample sizes and the varying definitions of RI and bleeding. An important finding of recent studies is that doses of eptifibatide and tirofiban are not always adjusted for RI, resulting in an increased risk of bleeding. The presence of RI in patients undergoing PCI should not preclude the use of GPRAs; however, the dose should be adjusted (eptifibatide and tirofiban) if pertinent and bleeding should be closely monitored.