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Intra-Procedural Stent Thrombosis Rare, Associated with Adverse Events
Researchers have found that intra-procedural stent thrombosis during PCI occurs in 0.7% of patients, but is strongly associated with subsequent out-of-lab stent thrombosis and mortality.
In the study, researchers conducted a frame-by-frame review of angiograms from the ACUITY and HORIZONS-AMI trials for intra-procedural stent thrombosis and evaluated its relationship with events at 30 days and 1 year.
Intra-procedural stent thrombosis occurred in 47 (0.7%) of 6,591 patients, and was associated with STEMI, higher white blood cell count, treatment of thrombotic and bifurcation lesions, bivalirudin monotherapy, bail-out glycoprotein IIb/IIIa inhibitor use and implantation of bare-metal (rather than drug-eluting) stents.
Major adverse ischemic events were higher in patients with vs. without intra-procedural stent thrombosis, specifically for mortality at 30 days (12.9% vs. 1.4%; P<.0001) and 1 year (12.9% vs. 3.1%; P<.0001).
Out-of-lab stent thrombosis also occurred more often among patients who had intra-procedural stent thrombosis at 30 days (17.4% vs. 1.8%; P<.0001) and 1 year (19.9% vs. 2.7%; P<.0001). It was also independently associated with 1-year mortality (HR=3.86; 95% CI, 1.66-9.00).
Although intra-procedural stent thrombosis is recognized and can be treated immediately in the cath lab, its occurrence portends nearly the same adverse prognosis in terms of early and late mortality as out-of-lab stent thrombosis, researchers noted.
“These observations are further justification as to why [intra-procedural stent thrombosis] should be considered a new classification of [stent thrombosis] ([Academic Research Consortium] or otherwise) and reported in all cases,” they concluded.
Perspective
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This interesting study is in line with previous observations by the same group and others. In a 2012 paper in the Journal of the American College of Cardiology, the same group reported intra-procedural thrombotic events (IPTE), including no-reflow, slow reflow or distal embolization as part of the definition from ACUITY and linked it to poor outcomes. They now report on intra-procedural stent thrombosis (IPST) from ACUITY and HORIZONS-AMI identified by an independent core laboratory using frame-by-frame analysis and its relation to outcomes. Earlier work by Biondi and colleagues (Biondi-Zoccai GG. Am J Cardiol. 2005;95:1466-1468) supports their same observations that the patient who develops an intraprocedural thrombotic event is an ultra-high-risk patient who has poor outcomes.
Several variables may influence the prothrombotic state of these patients. One obvious factor is a lack of antiplatelet effect at the time of PCI since stent thrombosis is a “platelet-centric” problem. The other variable is existing thrombus burden, which is greatest in STEMI. In the setting of massive thrombus, bivalirudin alone may not provide sufficient antiplatelet effects to prevent IPTE and IPST. In HORIZONS-AMI, 30-day stent thrombosis was associated with lack of heparin upstream and a low clopidogrel loading dose (Dangas G. J Am Coll Cardiol. 2009;54:1438-1446). The detection of these prothrombotic patients may be enhanced by objective testing of platelet function and procoagulant properties. The elevated white blood cell count cited as a risk factor for IPST may also contribute to a protrombotic state, since leukocytes are an important source of tissue factor and mediators that influence platelet function. Interestingly, the randomization to glycoprotein IIb/IIIa inhibitors (GPI) appeared protective against IPST. GPI are the most potent inhibitors of platelet function and have anti-inflammatory effects as demonstrated in the CLEAR PLATELETS Study (Gurbel PA. J Am Coll Cardiol. 2006;48:2186-2191). Importantly, GPIs provide immediate and profound platelet inhibition to all agonists — there is no pharmacodynamic “resistance” to these agents. However, it takes at least 6 hours for a 600 mg clopidogrel load to reach its zenith effect and that effect remains far less potent and much more variable than a GPI.
Also important is the authors’ observation that “bailout” GPI really only “bails out” less than 50% of patients in whom IPST develops. If one uses restoration of TIMI 3 flow as a criterion for successful “bailout,” only 44.7% with IPST had TIMI 3 flow restored. Therefore, even though GPIs produce predictably potent platelet inhibition, once the thrombus occurs and is massive enough to be identified by angiography, the ‘horse has left the barn’ and is already out of the pasture. The interventionalist should never believe that using a GPI only when a catastrophe (eg, IPST) occurs is the optimal way to use these agents. The authors clearly show that mortality is increased in patients with IPST. One major goal of interventional cardiology is to prevent IPST before it ever becomes evident. Based on the authors’ large body of data, administration of a GPI only after the catastrophe appears to be a suboptimal therapeutic approach.
The authors assert that, “Thus, future studies are warranted to determine whether combining a more potent adenosine diphosphate antagonist with bivalirudin might reduce IPST as well as acute ST and thereby further improve outcomes in patients with ACS.” However, the data they present suggest a protective effect of GPI. A strategy of using short course GPI (to minimize bleeding) until the full pharmacodynamic effect of an oral antiplatelet regimen occurs appears equally warranted for future study, particularly given the emerging data showing a delayed pharmacodynamic effect of the potent new oral P2Y12 inhibitors in the ACS patient (Alexopoulos D. Circ Cardiovasc Interv. 2012;5:797-804). In the STEMI patient taken directly for PCI, there is not enough time for any oral P2Y12 inhibitor to achieve its maximal pharmacodynamic effect before the stent is implanted.