New Pharmacological Adjuncts for Coronary Stenting: Can New Anticoagulants Improve Outcomes?

The purpose of this review is to discuss the use of new adjunctive pharmacological agents to improve the outcome of patients with obstructive coronary disease treated with stents. The goal of any form of adjunctive therapy is to improve procedural, in-hospital, and long-term outcome. In terms of stenting, this goal may be accomplished by developing strategies to prevent procedural and postprocedural thrombosis and to prevent postprocedural intimai hyperplasia. Recent studies suggest that more potent anticoagulant agents, particularly the new antiplatelet agents, may have an important role in this regard. High risk subsets in whom benefits may be more striking, including both clinical risk factors (acute MI, unstable angina, vein graft disease, and diabetes) and procedural risk factors (visible thrombus, uncovered persistent dissections, overlapping stents, suboptimal deployment, poor distal run-off, and “bail-out” use). Current “standard” anticoagulant therapy for stent placement would include aspirin, heparin, ticlopidine, and possibly (though much less popular now than previously) coumadin. More recent newer adjuncts include low molecular weight heparin, platelet IIb/IIIa antagonists (such as ReoPro), and thrombolylic agents. A number of other potential agents may find their way into clinked usage in the not-too-distant future. Adjunctive therapy can be considered not only for use “prophylactically”, prior to the procedure in high risk cases, but intraprocedurally for clinical situations or complications that may arise. There is increasing experience and an increasing comfort level with ReoPro usage in stent cases. Platelet GP IIb/IIIa-targeted therapy appears to be a useful adjunct to high risk stent procedures, Intraprocedural versus prophylactic administration of IIb/IIIa-targeted therapy in this setting continues to be highly controversial. Its utility in low risk settings is unknown, but will be clarified by ongoing clinical trials. A large number of additional exciting new pharmacological agents will be entering clinical trials in the very near future. Summary Obviously, we are working at the fringes of our knowledge as we “push the envelope” of stenting and as we begin to incorporate new forms of adjunctive therapy. In the absence of hard data from randomized controlled trials, we make clinical decisions on the best information we have available at the time. What do we know at present? 1. Platelet GP IIb/IIIa-targeted therapy does appear to be a useful adjunct for certain high risk stent procedures. 2. Intraprocedural versus prophylactic administration of IIb/IIIa-targeted therapy as an adjunct to stent procedures continues to be highly controversial. 3. The utility of IIb/IIIa-targeted therapy for low-risk stent procedures is unknown at present, but will be clarified by ongoing clinical trials. 4. A large number of exciting new pharmacological agents, including oral and IV thrombin inhibitors, oral and IV IIb/IIIa blockers, tissue factor pathway inhibitor, adhesion molecule blockers, and other new anti-platelet agents will be undergoing clinical trials with stents in the very near future. With this information in hand, we can hopefully apply adjunctive therapy (regardless of the specific agent used) in a rational, efficacious, and cost-effective manner. We have learned a lot in recent years, especially about how much more we need to learn. Empiricism and controlled clinical trials only go so far on their own. By judiciously and critically evaluating the information in hand, we can continue to advance the safety and efficacy of intracoronary stents.