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Patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) face increased risk of early stent thrombosis in the presence of high thrombus burden with certain pathological traits or suboptimal stenting, according to findings from an autopsy study published online April 23, 2014, ahead of print in the Journal of the American College of Cardiology. Refinements in procedural technique and stent design may help reduce the risk of early events, the authors suggest.

Researchers led by Renu Virmani, MD, of the CVPath Institute (Gaithersburg, MD), used light microscopy and morphometric analysis to evaluate 67 stented coronary lesions from 59 patients who presented with ACS and died within 30 days of implantation. All cases were derived from an autopsy stent registry obtained from medical examiners and hospital-based pathologists submitted for diagnostic consultation between 2004 and 2012.

Early stent thrombosis was identified in 37 lesions from 34 patients (58%), all of whom died of stent-related causes. Of 25 patients without stent thrombosis, cause of death was stent-related in 3 (distal dissection, coronary perforation, and side branch occlusion secondary to stenting). ECG readings at the time of diagnosis revealed STEMI in 16 patients and NSTEMI in 13 patients.

All 33 patients for whom pathological information on the myocardium was available had MI on histologic examination. 

Lesion Characteristics Implicated 

No differences emerged between lesions with (n = 37) or without (n = 30) stent thrombosis in terms of stent location in the coronary tree, duration of the implant, stent type (BMS vs DES or among DES types), number of stents or total stented length, or the underlying pathological findings (eg, plaque rupture, erosion, or calcified nodule).

However, in the stented segment, the maximum index thrombus thickness at the site of greatest thrombus burden was larger and necrotic core prolapse and occlusive thrombus in the side branch were more common in thrombotic lesions compared with patent lesions. Stenting in a false lumen secondary to medial dissection was numerically higher in thrombotic lesions (table 1).

Table 1. Lesion Characteristics: Thrombosis vs Patent

 
In nonstented segments proximal and distal to the stented segments, severe stenosis (> 75% cross-sectional narrowing), necrotic core prolapse, and medial dissection were more common in thrombotic than patent lesions, but the differences did not reach statistical significance.

Comparison of culprit and nonculprit sections within lesions showed that the extent of necrotic core prolapse, medial tear, and incomplete apposition was higher in sections with thrombus. In particular, independent predictors of stent thrombosis on multivariate analysis were:

• Maximum depth of strut penetration (OR 2.3; 95% CI 1.3-4.3; P = 0.006)
• Percentage of struts with medial tear (OR 1.8; 95% CI 1.3-2.4; P = 0.001)
• Percentage of struts with incomplete apposition (OR 1.8; 95% CI 1.4-2.4; P < 0.001)
  

In addition, plaque rupture was more common in arterial sections with vs without stent thrombosis (OR 2.2; 95% CI 1.5-3.2; P < 0.001).

In an accompanying editorial, Stephan Windecker, MD, and Crochan J. O’Sullivan, MD, both of Bern University Hospital (Bern, Switzerland), say the study “appropriately directs our focus to the pathophysiologic mechanisms of early (rather than late) [stent thrombosis] and reinforces the importance of procedural and lesion factors in mitigating… early [stent thrombosis] during ACS.”

Careful Technique, Improved Stent Designs May Help

The findings “emphasize the potential role of intracoronary imaging in describing the underlying plaque, quantifying the lesion extent, and assessing procedural results in terms of stent apposition,” Drs. Windecker and O’Sullivan write. They add that in the recent ADAPT-DES study, IVUS-guided PCI reduced the risk of definite/probable stent thrombosis compared with angiographic guidance, especially in ACS patients, with the benefit appearing early after PCI.

In addition, the editorial speculates that “necrotic core prolapse and medial tear may have been associated with high balloon inflation pressure, whereas incomplete apposition may have been more likely with low balloon inflation pressures during PCI.” Alternatively, they hypothesize, “the size and extent of the underlying ruptured plaque and necrotic core may incur a higher thrombogenicity.”

Improvements in stent design may help reduce stent thrombosis risk, the editorial says. For example, self-expanding stents may be less traumatic, lessening the chances of medial tear and deep penetration of stent struts into the necrotic core, while mesh-covered stents may help exclude thrombus and necrotic core prolapse. In fact, the thinner struts of newer-generation devices, which are less likely to cause arterial injury and promote more rapid endothelialization, may already have diminished the risk, Drs. Windecker and O’Sullivan add.

Finally, the contribution of thrombus burden to the development of stent thrombosis reinforces the importance of potent antiplatelet and anticoagulant strategies, they observe, adding that catheter-based thrombus aspiration “continues to deserve consideration in selected patients.”

Early Stent Thrombosis Especially Deadly

In a telephone interview with TCTMD, George D. Dangas, MD, PhD, of Mount Sinai Medical Center (New York, NY), said it is particularly important to explore the factors contributing to early stent thrombosis because events within the first 30 days after PCI are far more likely to be fatal than later cases. Thus, when it comes to taking steps to minimize stent thrombosis, “the biggest bang for your buck [is] in the subacute window,” he observed.

Dr. Dangas agreed that IVUS is a useful tool for mitigating stent thrombosis risk. The imaging method not only helps guide stent placement and confirm stent apposition but can also identify any dissections and assess the final lumen size. In addition, he advised careful attention to the degree of balloon pressure before stenting, but afterward, he said, higher pressures “are a good thing” because they help optimize implantation.

Another key to lowering stent thrombosis rates is giving optimal anticoagulant and antiplatelet agents, he posited, adding that that they should be administered as soon as possible after initial medical contact because any delay increases the risk.

Most studies of stent thrombosis are limited by the relative rarity of the event today, Dr. Dangas commented. Ongoing research is important to continue to uncover and evaluate the contributing factors, he concluded.

Study Details

Age, sex, indication for PCI, and past medical history were similar between subjects with and without stent thrombosis.

2. Windecker S, O’Sullivan CJ. Mitigating the risk of early stent thrombosis [editorial]. J Am Coll Cardiol. 2014;Epub ahead of print.

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