Stent Thrombosis – A Complication Best Avoided

Stent thrombosis (ST), while infrequent, is a serious complication of percutaneous coronary intervention (PCI) resulting in myocardial infarction (MI) or death.^1–4 While drug- eluting stents (DES) have reduced the rate of restenosis and target lesion revascularization by 50–70% as compared to baremetal stents (BMS), there have been some concerns regarding ST.^5,6,9–12 Systematic reviews of randomized trials revealed no overall differences relative to death with DES during longterm follow up to 5 years, but did show an increase in very late ST with DES.^7–9 A recent large multicenter registry reported the cumulative rate of ST following DES implantation of 2% at 3 years.10 The incidence of MI in patients with ST ranges from 66–100% with DES, and 60–87% with BMS.^1–4,11,12 Mortality after ST is also high, ranging from 11–45% depending on the definition of ST in the studies.^3,12,19 Primary PCI, preferably with the performance of intravascular ultrasound (IVUS) to evaluate possible causes of ST, is the treatment of choice for ST.¹³ Balloon angioplasty with possible thrombectomy is the preferred treatment, with implantation of a second stent reserved for residual dissections.¹³ Glycoprotein (GP) IIb/IIIa inhibitors should be strongly considered unless contraindications exist.^14–16 Platelet aggregation studies, though currently not standardized, should also be considered, and if insufficient platelet inhibition is detected with standard dual-antiplatelet therapy, an increased dose of clopidogrel at 150 mg per day can be recommended.¹⁷
In this issue of the Journal, DeVita et al have compared thrombus aspiration (TA) with standard PCI (SP) for the treatment of ST, and evaluated both immediate angiographic outcomes and inhospital major adverse cardiac events (MACE).¹⁸ The study enrolled 28 patients with ST over 2 years. Twelve patients underwent SP (15 procedures) and 16 patients underwent TA (18 procedures). Patients were enrolled regardless of stent type, date of implantation or clinical presentation, and the patients were treated either with SP or TA at the operator’s discretion. The angiographic analyses performed were antegrade coronary flow according to standard thrombolysis in myocardial infarction (TIMI) criteria, corrected TIMI frame count (cTFC), thrombus score (TS) according to the TIMI study group, angiographic features consistent with a high thrombus burden in the infarct-related artery, distal embolization and myocardial blush grade (MBG). Postprocedural adverse angiographic outcome was defined as the occurrence of TIMI 0–1 flow and/or angiographically- evident distal embolization. Evaluation of clinical outcomes was limited to inhospital clinical follow up only and recorded death, MI and target lesion revascularization.
All patients were treated with heparin, aspirin and clopidogrel (600 mg load followed by 75 mg/day). Abciximab was administered unless contraindicated. Balloon angioplasty alone was performed in the SP group. The Diver CE thrombus aspiration catheter (Invatec, Roncadelle, Italy) was mostly used in the TA group followed by balloon angioplasty. It should be noted that the Diver CE catheter is not available for sale in the United States. Additional stent implantation was used in both groups if there was residual stenosis or dissection.
Ninety-four percent of the procedures were performed for ST-elevation MI. Abciximab was used in 27% of the patients in the SP group and 39% of the patients in the TA group. DES led to stent thrombosis in 5 patients in each of the two groups, while BMS caused the stent thrombosis in 10 patients in the SP group and 13 patients in the TA group. Stent thrombosis was early (< 30 days) in 15 patients in the SP group, and 12 patients in the TA group and was late (> 30 days) in 6 patients in the TA group. There were no patients with late stent thrombosis in the SP group. The left anterior descending artery (LAD) was the culprit vessel in 33% of the patients in the SP group and 61% of the patients in the TA group. Baseline angiograms in the SP and TA groups showed TIMI 0–1 flow in 100% and 89% of patients (p = 0.28), and a cTFC of 100 ± 0 and 92.4 ± 22.6 (p = 0.19) in the two groups, respectively. Postprocedure adverse angiographic outcomes were noted in 5 (33%) patients in the SP group compared to 1 (5%) patient in the TA group (p = 0.04). There was a trend in favor of the TA group as compared to the SP group in post-PCI TIMI 3 flow (67% vs. 89%; p = 0.10), final cTFC (31 ± 35 vs. 17 ± 21; p = 0.10), and MBG 2–3 rate (40% vs. 67%; p = 0.12). The incidence of MACE was 33% in the SP group compared to 6% in the TA group, but this difference did not achieve statistical significance (p = 0.08). Two patients died in the SP group and there were no deaths in the TA group. It should be mentioned that 4 patients in the TA group, who had a TS > 3 after TA, were also treated with distal filter protection. However the postprocedural composite angiographic outcome, when the TA group (minus the 4 distal protection patients) was compared with the SP group, remained largely unchanged (7% in TA vs. 33% in SP; p = 0.05).
While the study separates out the patients in two groups receiving either SP or TA, a notable improvement on earlier studies, it is hampered by the small sample size, short clinical follow-up period and lack of randomization. None of the patients underwent IVUS to attempt to determine a possible cause for the ST.^22,26,27 The rate of GP IIb/IIIa inhibitor use is also low in this study. The study does not reveal if patient and/or procedural issues, e.g., compliance, aspirin or clopidogrel resistance, hypercoagulable states, stent malapposition, stent fracture, etc., led to the ST, which may be important in determining further therapy.^19–22 It is possible that postprocedural angiographic criteria including the cTFC, TIMI 3 flow rate and MBG may have achieved statistical significance with a larger sample size.
Future prospective studies, such as the PROTECT trial, which is a large randomized trial of 8800 patients comparing the frequency of ST between zotarolimus (Endeavor , Medtronic, Inc., Minneapolis, Minnesota) and sirolimus (Cypher^™, Cordis Corp., Miami, Lakes Florida) DES, will hopefully shed some light on the optimal management of these patients. Until then, our opinion is that ST is a complication that is best avoided, as best one can! We recommend caution against treating high-risk lesions and/or patients, specifically noncompliant patients at risk for premature antiplatelet therapy discontinuation, renal failure, diabetes and bifurcation lesions.^19–24 Until further trial data become available, if ST does occur, we recommend emergent PCI with TA and IVUS of the stent and use of GP IIb/IIIa inhibitors; evaluation for aspirin and clopidogrel resistance and consideration for higher-dose aspirin (325 mg rather than 81 mg daily) and clopidogrel (150 mg rather than 75 mg daily) and more prolonged dual-antiplatelet therapy.^25,26 It goes without saying that these patients will, of course, need close long-term clinical follow up.