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Unstable Plaque in Stents Spells Danger Over Time

— The causes of very late stent thrombosis are intensely debated, but new research leans toward a rupture in plaque buildup inside the stent.

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The causes of very late stent thrombosis are intensely debated, but new research leans toward a rupture in plaque buildup inside the stent.

Of the 27 patients who received drug-eluting stents (DES) and experienced very late stent thrombosis, 63% (17) were associated with in-stent neointimal rupture, a rate much higher than in previous studies, according to Seung-Jung Park, MD, of the University of Ulsan College of Medicine in Seoul, South Korea, and colleagues.

Action Points

  • Optical coherence tomography imaging indicated that advanced neoatherosclerosis with neointimal rupture and thrombosis was found to be a common mechanism of definite very late stent thrombosis.
  • Lesions with neointimal rupture showed a high frequency of ST-segment elevation myocardial infarction.

In addition, two-thirds of the patients with ruptured lesions presented with ST-segment elevation myocardial infarction (STEMI), suggesting "that advanced neoatherosclerosis was a common and aggressive mechanism of very late stent thrombosis," they wrote in the June issue of JACC: Cardiovascular Imaging.

The researchers suggested two possibilities for the discrepancy in the rate of neointimal rupture.

First, it could be due to the longer follow-up time between DES implantation and the thrombotic event (median 5 versus 2.5 years for other studies), as the "formation of in-stent neoatherosclerosis is time dependent."

The second reason could be that, unlike previous studies, Park and colleagues imaged stents before thrombus aspiration, potentially capturing more cases of neointimal rupture compared with those who aspirate first.

They noted that aspirates from very late stent thrombosis lesions have been shown to "frequently contain fragments of atherosclerotic intima and thin fibrous cap."

Park and colleagues therefore suggested that "the simple protocol decision to perform thrombectomy first or [imaging] first would affect the diagnosis of the cause of very late stent thrombosis and the published findings," giving credence to their higher rate of rupture.

In this study, as in others examining properties of stents associated with stent thrombosis, the intra-arterial imaging technique employed was optical coherence tomography (OCT).

The 33 patients in the study constitute the largest patient cohort with definite very late stent thrombosis reported so far, the researchers said.

Of the total cohort, 27 received DES and six received bare metal stents (BMS). All of the BMS-treated lesions showed neointimal rupture compared with two-thirds of DES.

Park and colleagues noted in their previous work using intravascular ultrasound they found that "stent malapposition was unique to DES-related very late stent thrombosis, while in-stent neointimal rupture was found in both BMS and DES in cases of very late stent thrombosis."

In the current study, the researchers found 52% (14) of DES-treated lesions that ruptured also were malapposed to the arterial wall. A total of 22% (six) showed both neointimal rupture and malapposition.

However, thrombus was more associated with rupture than malapposition, they pointed out. None of the lesions fortified with BMS were malapposed.

Three DES exhibited fractures and they were associated more with neointimal rupture than malapposition.

"This suggests an interrelationship among neoatherosclerosis, restenosis, very late stent thrombosis, and stent fracture in some patients," they wrote.

The median follow-up was about 5 years for DES-treated lesions and approximately 9 years for patients with BMS. The median age for DES patients was 57 and 70 for BMS. Most of the patients in both groups were men.

Another significant finding was that a TIMI flow grade of 3 was associated with a less frequent rate of neointimal rupture (22% versus 63%).

The stents examined in the study included 22 Cypher, three Taxus, and one Xience.

Limitations of the study included its cross-sectional observational nature, absence of a control group, and small sample size that precluded any subgroup analysis. In addition, potential interference from imaging artifacts might under- or overestimate findings and there was a lack of proximal or distal reference segments.

From the American Heart Association:

Disclosures

The study was supported by Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, and by the Cardiovascular Research Foundation, Seoul, Republic of Korea.

Kang had no conflicts of interest to report. One co-author reported relationships with Boston Scientific, Volcano, InfraReDx, and St. Jude. All other authors reported they have no relationships relevant to the contents of this paper.

Primary Source

JACC: Cardiovascular Imaging

Kang SJ, et al "OCT analysis in patients with very late stent thrombosis" J Am Coll Cardiol Img 2013; 6: 695-703.