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Patients who develop stent thrombosis during the index hospital stay after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have higher mortality and bleeding rates than those whose events occur after discharge, according to an analysis of the HORIZONS-AMI trial published in the May 15, 2012, issue of the Journal of the American College of Cardiology.

For the multicenter HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in AMI) trial, 3,602 STEMI patients undergoing primary PCI were randomized to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Then 3,006 of the patients were randomly assigned in a 3:1 ratio to receive a Taxus paclitaxel-eluting stent (n = 2,257; Boston Scientific, Natick, MA) or an otherwise identical BMS (n = 749). Among them, 156 (4.9%) developed Academic Research Consortium-defined definite or probable stent thrombosis during 3 years of follow-up.

Earlier Events More Risky

For the current post-hoc analysis, researchers led by George D. Dangas, MD, PhD, of the Mount Sinai Medical Center (New York, NY), compared clinical outcomes according to whether the stent thrombosis occurred in-hospital (n = 54) or out-of-hospital (n = 102). The median times to stent thrombosis were 1 day (interquartile range [IQR], 0-5 days) and 360 days (IQR, 100 to 604 days), respectively.

Patients with in-hospital stent thrombosis had higher rates of both mortality and major bleeding at 1 year after their event but a lower rate of MI (table 1).

Table 1. Clinical Outcomes 1 Year After Stent Thrombosis

Multivariate analyses showed that in- vs. out-of-hospital stent thrombosis was a powerful predictor of 1-year mortality (HR 4.62; 95% CI 1.98-10.77; P = 0.0004). Current smoking, final post-PCI TIMI flow grade 3, and bivalirudin vs. heparin plus GPI use also significantly predicted mortality.

“Conceptually, the prognosis following [stent thrombosis] may depend on how rapidly reperfusion is restored. One might presume that out-of-hospital [events] would have a more dire prognosis than [those] occurring in-hospital due to the absence of readily available resuscitation or coronary angiography/PCI capabilities,” the investigators note. However, the findings do not bear out this hypothesis.

Unexplained Factors at Work

Morton J. Kern, MD, of the University of California, Irvine (Irvine, CA), told TCTMD in a telephone interview, “This is sort of a counterintuitive result.”

“You would think that people who have a stent thrombosis out of the hospital would drop dead more, because you couldn’t rescue them, or you couldn’t find them or get to them,” he commented. The mechanisms behind early and late thrombosis are totally different, Dr. Kern added, noting that the reason for the increased mortality with in-hospital thrombosis is likely multifactorial.

For in-hospital stent thrombosis, Dr. Kern said, the problem is likely to be either related to details of the PCI or to the degree of anticoagulation. “I don’t think there is anything to do except ensure that your technical aspects of stent implantation are well done,” he advised.

Similarly, the paper notes that early events are most likely related to technical and procedural factors, “whereas delayed neointimal coverage and ongoing vessel inflammation are associated with very late [stent thrombosis].”

Frailty Upsets the Balance

In an accompanying editorial, Lloyd W. Klein, MD, and Carlos Arrieta-Garcia, MD, both of the Advocate Illinois Medical Center (Chicago, IL), agree that the causes of early and late stent thrombosis are disparate. The fact that major bleeding was not a significant predictor of mortality in this analysis suggests a confounding variable that has not been measured, they say.

“There is some common systemic factor at play that is upsetting the fragile balance between clotting and bleeding, as that is the most apparent pathophysiologic connection among these conditions,” they write, suggesting patient frailty as the missing variable.

Frailty is difficult to assess objectively, but previous work has led to a 5-item combination of unintended weight loss, exhaustion, physical activity, time required to walk 15 feet, and hand grip strength. “Future pharmacologic studies, PCI clinical trials, and registries such as the National Cardiovascular Data Registry should be amended to include simple subjective clinical variables such as frailty that have not been collected traditionally due to the difficulty in their objective definition,” Drs. Klein and Arrieta-Garcia write.

Dr. Dangas and colleagues note several limitations to their analysis, especially its retrospective design and lack of information on antiplatelet hyporesponsiveness. The fact that PCI was performed during STEMI could also have raised stent thrombosis rates and worsened associated outcomes. “Further studies are required to determine whether an early in-hospital [stent thrombosis] event may be less catastrophic in patients undergoing elective stent implantation,” they suggest.

Study Details

Mean length of stay was 8.67 ± 6.63 days in the in-hospital group and 5.65 ± 5.86 days in the out-of-hospital group (P < 0.01). Patients with in-hospital stent thrombosis were more likely to have pre-PCI coronary TIMI flow grade 0 or 1 and thrombocytopenia, and they were less likely to have received heparin before randomization. Their peak creatinine phosphokinase levels during the original STEMI also were higher. In the out-of-hospital group, there were more current smokers as well as more patients with a history of diabetes.

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

2. Klein LW, Arrieta-Garcia C. Is patient frailty the unmeasured confounder that connects subacute stent thrombosis with increased periprocedural bleeding and increased mortality? J Am Coll Cardiol. 2012;59:1760-1762.

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