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In 1979, Andreas Gruentzig reported his experience with the first 50 coronary angioplasty procedures. In those first 50 patients, antiplatelet therapy was empiric and consisted of 1.0 g of aspirin (approximately 65 mg) for 3 days and dextran during the procedure. In the 36 years since that publication, the scientific understanding of arterial thrombus formation in response to arterial injury and clinical experience with pharmacologic means to mitigate this process have grown by immeasurable proportions. Specifically, the understanding of surface receptors and ligands necessary for the transformation of platelets to their active state, as well as the surface proteins responsible for adherence to fibrin, leukocytes, and other platelets, has facilitated the development of therapies targeted to specific steps in the activation sequence. Clinical investigation and experience continually refine the circumstances under which specific therapies are best applied in order to maximize benefit and minimize risk. In contemporary coronary angioplasty, the interplay between arterial wall, platelets, plaque components, clinical presentation, stent design, stent components, and concomitant medications has resulted in a complex and fluid therapeutic algorithm for antiplatelet therapy before, during, and after percutaneous coronary interventions.
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HISTORICAL PERSPECTIVE
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From the initial angioplasty procedure in 1977 through the introduction of coronary stents in the early 1990s, thrombosis at the site of angioplasty was recognized as a primary mediator of acute vessel closure during and immediately after the procedure. Heparin was empirically used successfully during and in the immediate periprocedural period, but only aspirin was administered at patient discharge. In the earliest experience with intracoronary stents in the early 1990s, stent thrombosis rates approached 20% and became a focus of postprocedure care. The empiric approach of universal oral anticoagulation with warfarin following stent implantation reduced the incidence of stent thrombosis to 3% to 5%, but at a significant cost of access site–related and non–access site–related bleeding complications. Some operators even suggested that the thrombotic risk of stents was too excessive to justify routine use.
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In 1995, a landmark study changed stent practice and shifted pharmacologic strategy from antithrombotic to antiplatelet following percutaneous coronary intervention (PCI). After initial observations that 80% of stents were inadequately expanded when examined by intravascular ultrasound (IVUS), Colombo and colleagues elegantly demonstrated that full stent expansion with apposition to the artery wall was both necessary and sufficient for patients to be safely treated with 2 antiplatelet medications (aspirin and ticlopidine) rather than warfarin. The calculus again changed substantially with the introduction of drug-eluting stents. Although the benefits of a durable revascularization result have been well documented, the combination of delayed healing and polymer hypersensitivity made these stents more susceptible to late thrombosis and lengthened the duration of antiplatelet therapy after PCI.
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Twenty years of clinical studies of coronary stent procedures have resulted in the following principles of contemporary PCI with regard to antiplatelet therapy: (1) stent thrombosis is platelet mediated and carries a high morbidity and ...