Antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting.

PURPOSE: Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and stenting are reviewed. SUMMARY: Up to 8% of patients undergoing PCI have AF and thus require both antiplatelet and anticoagulation therapies, which put them at increased risk for bleeding. Current literature suggests that using a single antiplatelet agent in combination with oral anticoagulation with a direct-acting oral anticoagulant (i.e., dual therapy) is effective and associated with less bleeding risk than triple therapy (dual antiplatelet therapy plus an oral anticoagulant) in patients with AF undergoing PCI with stent placement. The most recently studied dual therapy regimens consist of clopidogrel in combination with apixaban, rivaroxaban, or dabigatran. Guidelines recommend use of an oral anticoagulant plus clopidogrel and aspirin for a short period of time. In general, aspirin should be discontinued in most patients at discharge. In patients with a high risk of thrombosis, aspirin can be continued for up to 1 month. Dual therapy should be continued for 12 months, with oral anticoagulant monotherapy continued thereafter. CONCLUSION: A review of current literature on antithrombotic therapy in patients with AF undergoing PCI and subsequent coronary artery stenting indicates that the favored regimen is dual therapy consisting of clopidogrel with rivaroxaban, apixaban, dabigatran, or a vitamin K antagonist. Aspirin may be used in the periprocedural period but should be discontinued thereafter to reduce the risk of bleeding. Decisions regarding specific agents and duration of treatment should be based on thrombotic risk, bleeding risk, and patient preference.

How well can a T-cell epitope replace its parent carrier protein? A dose-response study.

PURPOSE: This work examines the effectiveness of synthetic peptide immunogens derived from immunodominant T-cell epitopes as replacements for their intact parent protein in vaccines. METHODS: Fluorescein was conjugated to hen egg lysozyme (FL-HEL, positive control) and three synthetic peptide immunogens: (a) murine B10.A (H-2a) immunodominant T-cell epitope of HEL [FL-(T-cell epitope)]; (b) multiple antigenic peptide (MAP) multimer of this epitope ([FL-(T epitope)]n-MAP, n = 2-4); and (c) negative control MAP with T-cell epitope residues replaced with glycine [(FL-Gly18)4-MAP]. The dose response of each immunogen was examined over a 300-fold range in B10.A mice. The immune response was monitored using antifluorescein ELISA assays. RESULTS: FL-(T epitope)'s immune response correlated positively with dose, with maximum response comparable to that of [FL-(T epitope)]n-MAP, or FL-HEL. This trend was consistent across 1 degrees, 2 degrees, and 3 degrees responses, although interanimal variability was higher in the latter two because of an all-or-none response in mice immunized with this peptide. [FL-(T epitope)]n-MAP's immune response was consistently high and nearly dose independent, a trend observed across 1 degrees, 2 degrees, and 3 degrees responses. FL-HEL's immune response correlated negatively to dose in the 1 degrees response but was nearly dose independent in the 2 degrees and 3 degrees responses. The magnitude of these latter responses was comparable to that observed for [FL-(T epitope)]n-MAP. (FL-Gly18)4-MAP did not elicit an immune response except at the highest dose. This trend was consistent across 1 degrees, 2 degrees, and 3 degrees responses. CONCLUSIONS: The monomeric epitope was 300-fold less potent than its parent carrier protein, but increasing immunogen valency using MAP technology compensated totally for reduced potency. (FL-Gly18)4-MAP's lack of response at all but the highest dose strongly suggests that a specific immunodominant T-cell epitope sequence for HEL is necessary for successful peptide mimicry of HEL. This work also demonstrates the importance of quality assessment of commercial MAP core resins.