Department of Internal Medicine, Division of Cardiology, University of Heidelberg, Heidelberg, Germany
Correspondence and offprint requests to: Priv. Doz. Dr C. Haller, Department of Internal Medicine III, University of Heidelberg, Bergheimerstr. 58, 69115 Heidelberg, Germany.
Introduction
Patients with renal failure, especially patients with end-stage renal disease, have high cardiovascular morbidity and mortality, to a large extent due to coronary artery disease. As a result uraemic patients frequently undergo coronary intervention, but the long-term outcome of percutaneous transluminal coronary angioplasty (PTCA) has been disappointing, mainly because of accelerated re-stenosis. A re-stenosis rate of up to 81% after initially successful PTCA has been reported, and even higher rates for repeat angioplasties [1]. In another study the 5-year cardiac-event-free rate was 70% in dialysis patients treated with coronary artery bypass grafting compared with only 18% in patients who had received PTCA [2]. Some authors concluded that PTCA may not be justified in patients with uraemic coronary artery disease because of an unacceptably high re-stenosis and cardiac-event rate [3].
Recently the placement of intracoronary stents during PTCA has become the procedure of choice for many types of coronary artery lesions, especially in proximal segments of the major coronary conduit vessels [4]. The implantation of stents has greatly reduced the need for emergency coronary artery surgery. The angiographic and clinical success rate of coronary stenting is superior compared with `simple' angioplasty [4,5], although diffuse in-stent-re-stenosis due to a proliferative response of the vascular wall remains a problem. Re-stenosis rates after stenting are mostly between 20 and 30%, but may exceed 50% in small vessels and complex lesions in patients with diabetes [6].
Role of antiplatelet therapy
The success of coronary artery stenting can be attributed to technical advances in stent deployment and most importantly to effective antithrombotic therapy. The latter is a precondition for successful stenting, since acute stent thrombosis is a recognized complication of intracoronary stents. In the early days of coronary stenting all patients received full therapeutic anticoagulation with heparin, starting immediately after stent implantation followed by oral anticoagulation with vitamin K antagonists. In addition to systemic anticoagulation platelet function was inhibited by aspirin. However, even full anticoagulation and aspirin did not completely prevent stent thrombosis. In the meantime we have learned that platelet-dependent mechanisms are more important than plasmatic coagulation in the pathogenesis of acute stent thrombosis. Therefore current stent regimens focus on the inhibition of platelet function.
The central event in platelet-induced thrombus formation is the binding of fibrinogen to the activated platelet surface via the membrane glycoprotein IIb/IIIa. This interaction of platelets and fibrinogen can be selectively inhibited by the monoclonal anti-gpIIb/IIIa antibody abciximab or by a variety of non-antibody drugs. Gp IIb/IIIa antagonists play an important role in the management of acute coronary syndromes and/or complications of angioplasty/stenting [7,8]. For routine stenting orally active drugs are generally preferred. The time-honoured antiplatelet drug is aspirin. It inhibits platelet function by irreversibly blocking cyclo-oxygenase, thereby inactivating the thromboxane pathway of platelets. Recently a new group of antiplatelet drugs, the thienopyridines, have been introduced into clinical practice. These compounds inhibit platelet function by interfering with the ADP-mediated activation of platelets. Like aspirin, the thienopyridines inhibit platelet function irreversibly, i.e. platelet inhibition persists until new platelets are released from the bone marrow. Unlike aspirin the thienopyridines are not active in vitro, since they have to undergo biotransformation into their active form in vivo. The first generation thienopyridine ticlopidine requires twice daily administration and may (rarely) cause bone marrow suppression; therefore monitoring the blood count is necessary during therapy with this substance. The newer thienopyridine clopidogrel does not induce this complication and may be given once daily. In coronary stenting it is current practice to prescribe aspirin and one of the thienopyridines. The dual inhibition of platelet function with aspirin and ticlopidine induces less bleeding complications than vitamin K antagonists [9] and effectively lowers the risk of coronary stent thrombosis [10]; more recently this benefit has also been shown for the combination of aspirin and clopidogrel [11].
Can stents improve the outcome of PTCA in uraemic patients?
Coronary artery stenting has clearly improved the immediate and long-term success rate of coronary angioplasty, although in-stent-re-stenosis remains a problem. Currently it is not clear whether the benefits of stenting also apply to the uraemic patient. Stents improve the immediate procedural results of PTCA by several mechanisms including diminished elastic recoil of the vascular wall and effective management of angioplasty-related coronary artery dissections. While these benefits should also apply to uraemic patients, other anatomic and/or pathophysiological factors which may be unique to uraemic coronary artery disease could be less amenable to stenting. Since the stenotic coronary lesions in patients with ESRD are often heavily calcified, `rota-stenting', i.e. a combination of rotational arterectomy and coronary artery stenting [12] may be a particularly useful interventional treatment option which warrants further evaluation in these patients.
In the overall patient population the single most important factor for stent success has been the improved management of thrombotic complications. Therefore one could argue that patients with renal failure derive only marginal benefit from the newer antiplatelet regimens, since platelet function is already impaired in uraemia. On the other hand, uraemic patients could be ideal stent recipients benefiting from the procedural success of stenting with a lower risk of stent thrombosis because of their compromised platelet function. It may even turn out that patients with chronic renal failure require less antithrombotic therapy for the prevention of stent thrombosis than other patients with arteriosclerosis, which could reduce drug-related complications and cost. One trial in non-uraemic patients has shown a similar short-term outcome in patients treated with aspirin alone compared to combined aspirin/ticlopidine therapy after optimized stent implantation [13].
Currently no data from prospective controlled trials are available on the long-term outcome of coronary artery stenting in uraemic stent recipients. Similarly no controlled evidence is available concerning the need for or risk of antiplatelet therapy in patients with renal failure. One retrospective analysis has shown that percutaneous coronary revascularization with new devices, e.g. stents, rotational arterectomy, is technically more successful than standard PTCA in patients with renal failure, but the significant comorbidity of these patients is reflected by the incidence of adverse cardiac events [14]. Other authors have reported a better outcome of coronary revascularization by stent implantation in uraemic patients [15]. The current clinical experience with coronary artery stenting in patients with renal failure is encouraging and should stimulate the further evaluation of interventional treatment options, in particular `rota-stenting', in uraemic coronary artery disease.
References