Current guidelines recommend dual antiplatelet therapy—a P2Y ₁₂ inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin—for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y ₁₂ inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.

Background: Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss‐of‐function (LOF) variant carriers versus non‐carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real‐world outcomes with the clinical implementation of CYP2C19 ‐guided antiplatelet therapy after PCI. Methods and Results: Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all‐cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life‐threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39–0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71–1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions: Real‐world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.

Background Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to α _v β ₃ integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds α _IIb β ₃ on platelets and α _v β ₃ on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly specific for α _IIb β ₃ . The conclusion that eptifibatide does not bind vascular α _v β ₃ integrins may be premature, however, because recent studies have demonstrated that the affinity of α _v β ₃ for various ligands, including antagonists, is subject to modulation. Methods and Results Abciximab and 7E3, the anti–β ₃ integrin monoclonal antibody from which abciximab was derived, bound α _v β ₃ on HASMCs in a specific and saturable manner and with an affinity similar to binding to α _IIb β ₃ on platelets. 7E3 and eptifibatide inhibited α _v β ₃ -mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on α _v β ₅ - or β ₁ -mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited α _v β ₃ -mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited α _v β ₃ -mediated responses to soluble TSP by HASMCs and β ₃ integrin–expressing HEK cells. Conclusions Eptifibatide and 7E3, but not tirofiban, specifically inhibit α _v β ₃ -mediated binding of human smooth muscle and endothelial cells.

Early reperfusion with percutaneous coronary intervention (PCI) or thrombolytic therapy remains the primary goal in the initial treatment of eligible patients presenting to a hospital with ST-elevation myocardial infarction (STEMI). Over the last decade, recognition that this strategy is of critical importance has prompted the development of a number of regional and national initiatives to facilitate and improve systems of care for STEMI. These initiatives, including the Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments initiative,¹ the American College of Cardiology (ACC) D2B Alliance,² and the American Heart Association (AHA) Mission: Lifeline initiative,³ have enhanced recognition, reduced time to treatment, improved systems of care, and facilitated access of patients to PCI-capable facilities. Consequently, national median door-to-balloon times improved by more than 30 minutes between 2005 and 2010.⁴