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Patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) are far more likely to suffer stent thrombosis during the first year after implantation than elective patients, and the event is fatal about one-third of the time, according to data published online October 25, 2011, ahead of print in Circulation: Cardiovascular Interventions.

The ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial was a multicenter study that randomized more than 13,819 moderate- and high-risk NSTE ACS patients managed with an early invasive strategy to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy. Patients in the first 2 groups were then randomized to routine up-front treatment with a GPI or bailout GPI use. Among patients who underwent PCI, the stent type—DES or BMS—was chosen at the operator’s discretion.

For this post hoc analysis, investigators led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), assessed the incidence, predictors, and clinical implications of stent thrombosis in the cohort of 7,162 patients who received at least 1 stent.

At 1 year follow-up, the Kaplan-Meier estimated rate of definite/probable stent thrombosis was 2.2%. Of that, 1.4% occurred early (within 30 days of implantation) and 0.8% occurred late (between 30 days and 1 year). Similar rates were seen in 3,405 patients included in a formal angiographic substudy (2.0% incidence overall, with 1.4% early and 0.6% late).

Dire Prognosis

Patients who experienced definite/probable stent thrombosis within 1 year had markedly higher rates of all-cause and cardiac mortality, MI, and TVR compared with those who remained free of stent thrombosis (table 1).

Table 1. One-Year Outcomes: Stent Thrombosis vs. No Stent Thrombosis

 
Similar results were seen when only definite stent thrombosis was considered. Increased risk of death, MI, and TVR was observed for both early and late episodes of stent thrombosis (all P < 0.001).

Factors That Do—or Do Not—Predict Stent Thrombosis

Rates of early, late, and cumulative 1-year definite/probable stent thrombosis were similar regardless of whether patients received DES (n = 4,633) or BMS (n = 2,529; 1-year rates, 2.2% and 2.3%, respectively; P = 0.38). Nor did the type of procedural antithrombotic therapy used affect the 1-year risk (2.3% for heparin plus a GPI, 2.4% for bivalirudin plus a GPI, 1.9% for bivalirudin alone; P = 0.39).

On multivariable analysis, insulin-treated diabetes, the number of diseased vessels, and ST-segment deviation of at least 1 mm were independent predictors of definite/probable stent thrombosis at 30 days and the cumulative incidence through 1 year, while insulin-treated diabetes was the only predictor of late stent thrombosis.

When angiographic variables were added to the model, patients with stent thrombosis at 1 year had more lesions and diseased vessels, and a greater extent of CAD. In addition, lesions that resulted in stent thrombosis were more likely to have:

• Coronary thrombus
• Abrupt closure during the procedure
• No reflow
• A smaller final minimal luminal diameter by QCA

When multivariable analysis was restricted to patients in the angiographic substudy, the extent of CAD per patient was the only independent predictor of cumulative 1-year definite stent thrombosis.

The authors acknowledge several limitations including the fact that the study is post hoc and the angiographic cohort may not have been large enough to detect some significant clinical correlates of stent thrombosis.

High NSTE ACS Risk Intuitive, and Now Proven

In a telephone interview with TCTMD, Dr. Stone said that although it is intuitive that stent thrombosis risk would increase on a sliding scale from stable disease through NSTE ACS and STEMI, it had not been previously documented for NSTE ACS.

“The gradient suggests that stent implantation in ACS is one of the highest risk factors for stent thrombosis,” he observed

Moreover, the incidence of stent thrombosis in this population is quite high, he noted. “It’s quite striking to see in this large trial with hundreds of international sites,” Dr. Stone said. “Were you to ask [the individual investigators] how frequently they see stent thrombosis, they would probably say, ‘Never or almost never.’ But here you see it’s 2.2% at the end of 1 year—that’s more than 1 out of 50 patients.”

The current findings underline the importance of atherosclerotic burden in estimating the risk of stent thrombosis, the investigators say, and suggest that the association of other clinical risk factors identified in previous studies may be explained by their correlation with more extensive coronary disease.

But according to Dr. Stone, the factors the study did not link to stent thrombosis may be as important as the predictors it did identify. For example, contrary to some earlier studies, there was no association between DES and increased stent thrombosis. Also, the choice of procedural anticoagulation regimen—in particular bivalirudin alone—did not affect stent thrombosis risk.

Furthermore, although it did not emerge from multivariable analysis, “we do believe that technique matters,” Dr. Stone observed. “We didn’t look at use of IVUS to guide optimal stent implantation, but numerous observational studies have suggested that achieving a minimal stent area—which is easier with IVUS—is important to avoiding stent thrombosis. We also think that high-pressure implantation and covering significant areas of reference vessel disease are important, because [some data] suggest that inflow and outflow stenosis is related to stent thrombosis.”

How to Minimize the Risk

Dr. Stone summed up the implications of the study for clinicians: First, recognize that NSTE ACS patients are at high risk for stent thrombosis and that its occurrence often has dire consequences; and second, take all steps to prevent it. These steps include:

• Meticulous technique
• Recognition that since bivalirudin does not increase stent thrombosis but does reduce major hemorrhage, its use should be preferred, especially in patients at moderate to high bleeding risk
• Use of DES that have been shown to minimize stent thrombosis, such as everolimus-eluting stents
• Use of more potent ADP antagonists such as prasugrel and ticagrelor in patients who are not at high bleeding risk

Such measures are unlikely ever to eliminate stent thrombosis altogether, Dr. Stone said, but that should be the goal.

Study Details

Per protocol, definite stent thrombosis was defined as angiographic thrombus or total occlusion within the stented vessel at the time of clinically driven angiography for ischemia. Probable stent thrombosis was defined as any death not attributed to a noncardiac cause or any Q-wave MI in the target-vessel area in the absence of documented angiographic stent patency. 

Note: Dr. Stone and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

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