Rising Like the Phoenix?

Depending on one’s perspective, αIIbβ3 antagonists can be viewed as a great success story or as an exasperating disappointment.1 Certainly, millions of patients have been treated with the 3 Food and Drug Administration–approved αIIbβ3 antagonists, abciximab, eptifibatide, tirofiban; based on their reduction in mortality in clinical trials, one can calculate that many lives have been saved by these drugs2 and they continue to be administered to prevent thrombotic events, primarily in the setting of percutaneous coronary interventions.3 However, the vision that αIIbβ3 antagonists would be broadly administered as safe, orally active agents to patients at risk for acute coronary syndromes, and other cardiovascular diseases not only failed to materialize but also were abandoned as being unsafe.4,5 Indeed, the perceived side effects of existing αIIbβ3 antagonists, bleeding,6,7 and thrombocytopenia,8–10 in combination with the emergence of alternative and inexpensive antiplatelet and antithrombotic drugs have led to waning use of αIIbβ3 antagonists during the past decade. Thus, the story of αIIbβ3 antagonists seems to be heading toward its closing chapter. To rewrite or extend the ending of this story would require development of a new class of αIIbβ3 antagonists, one with a distinct mechanism of action that would distinguish it …