Preventing Subacute Thrombosis

Gordon Pate, MB and John G. Webb, MD
Gordon Pate, MB and John G. Webb, MD
Since the advent of percutaneous coronary intervention (PCI), the possibility of sudden and unexpected coronary thrombosis has been a concern. Initially, these concerns were largely related to acute closure occurring during the initial 24 hours following balloon angioplasty; the consequence of inadequate dilation, recoil and dissection. The introduction of stents, while substantially reducing acute closure, gave rise to a new concern, subacute thrombosis (SAT). SAT is defined as occlusion at the stented site beyond 24 hours up to the now generally accepted period of 30 days. Reynolds et al. in this issue of the Journal of Invasive Cardiology identified a 1% rate of angiographically See Reynolds et al. on pages 364–368 documented SAT among 3295 interventions.1 This incidence is similar to data from other angiographic studies.2 Symptom-driven angiography tends to underestimate the true incidence of SAT. Patient follow-up in registries is often incomplete, occlusion may be silent and sudden death usually precludes angiography. Subacute thrombosis may alternatively be diagnosed clinically on the basis of sudden unexplained death or an unstable coronary syndrome, which may not always result in repeat angiography. A review of pooled data in 1996 suggested a clinical incidence of 4.3% following elective PCI.3 Intravascular ultrasound has clarified the potential role of sub-optimal stent deployment as a contributor to SAT and this has, to some degree, been addressed by more careful and aggressive stent deployment strategies.4 A more recent analysis of controlled trials suggests that the incidence of clinical stent thrombosis before 30 days has fallen to 0.9% since the advent of second-generation stents, high-pressure deployment and current anti-thrombotic regimens, with an incidence of 0.3% after 24 hours.5 The incidence is likely higher outside the setting of clinical trials. Stent thrombosis is a costly business. Substantial resources are already spent in prevention; on stents, which have reduced the incidence of both acute and subacute closure, and anticoagulation regimens, which have become more effective but are more expensive. Reynolds et al. estimated the cost of treating a patient with subacute thrombosis to be ~ $11,000, a figure not dissimilar to that of the treatment of acute myocardial infarction with primary PCI.6 How, then, can we improve matters? The risk factors identified for SAT are predictable and include longer stent length, smaller final minimum luminal diameter, extensive dissection, elevated platelet count, pre-procedural thrombus and presentation with acute coronary syndrome. Optimal stent deployment must be assured and patients with any of these risk factors should receive special attention with regard to anticoagulation. Optimal anticoagulation at the time of coronary stenting continues to be clarified. Aspirin and clopidogrel are routinely administered. That some individuals are resistant to low doses of aspirin is well established, but whether this places them at risk of subacute thrombosis is not known.7 Thienopyridine therapy is best initiated prior to stent implantation, although this is often not achieved.8 Heparin remains standard therapy, although concerns remain with regards to dose, monitoring and the potential for a rebound thrombotic tendency after discontinuation.9,10 Alternatives such as low molecular weight heparin and direct thrombin inhibitors, such as argatroban, are gaining interest. Glycoprotein antagonists reduce the risk of acute stent thrombosis.11–13 While these agents may reduce rebound thrombosis following heparin discontinuation, whether they themselves are also associated with a rebound thrombotic tendency is unclear.14 Abciximab binds permanently to platelet receptors so that restoration of platelet effect is largely dependent on the release of fresh platelets. This process may take several days. Platelet activity may be restored more rapidly due to upregulation of internalized glycoprotein receptors.15,16 There is some clinical evidence to suggest that abciximab reduces the risk of SAT.17 However, there are few data to allow comparison with other agents. Current aggressive anticoagulation regimens, while reducing SAT, are also associated with increased bleeding complications and, for this reason, it may not be possible to eliminate SAT entirely. For the moment, physicians must ensure that patients receive appropriate pre-medication, have optimal stent deployment and continue to receive evidence-based medications for an appropriate period despite the costs or inconvenience of therapy. In the absence of these assurances, the necessity and advisability of coronary intervention may be questioned.
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