Glycoprotein IIb/IIIa receptor inhibitors: Putting the EPIC, IMPACT II, RESTORE, and EPILOG trials into perspective
Clinical evaluation of the antiplatelet glycoprotein (GP) IIb/IIIa receptor antagonists has now extended over nearly a decade. The largest experience to date with this new class of agents has been in the prevention and management of complications of percutaneous coronary intervention. Four trials involving 3 different agents in the setting of coronary intervention are discussed: the Evaluation of c7E3 in Preventing Ischemic Complications (EPIC) and the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GPIIB/IIIA Receptor Blockade (EPILOG) trials of the antibody fragment abciximab (ReoPro); the Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II (IMPACT II) trial evaluating the peptide Integrilin; and the Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial studying the nonpeptide mimetic tirofiban (Aggrastat). All 3 agents reduced the incidence of clinically relevant endpoint events but to differing degrees and for varying durations. The increased rates of bleeding complications seen in the EPIC trial appear to be lessened by the use of competitive GP IIb/IIIa inhibitors and by studious titration of heparin and careful groin management. The findings in IMPACT II and EPILOG suggest that the entire spectrum of patients who undergo coronary intervention benefit from GP IIb/IIIa blockade. Based on the results of these trials, platelet GP IIb/IIIa integrin blockade appears to be instrumental in improving clinical outcomes following percutaneous intervention, with clinical benefit extending to all patient categories. Bleeding risks can be minimized by minor changes in standard patient care algorithms. Dosing strategies and treatment duration still need to be refined, especially for the competitive antagonists. The role of these agents as adjuncts in stenting and rotational atherectomy and as adjunctive therapy in other disease settings requires further study.