Does Therapeutic Hypothermia Cause Stent Thrombosis?

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco.

Source: Penela D, et al. Hypothermia in acute coronary syndrome: Brain salvage versus stent thrombosis? J Am Coll Cardiol 2013;61:686-687.

Therapeutic hypothermia (THT) in survivors of cardiac arrest due to shockable rhythm is associated with improved neurological outcomes. Acute coronary syndromes (ACS) are frequently the cause of cardiac arrest, and these patients often undergo percutaneous coronary intervention (PCI) during the index hospitalization. THT may be associated with alterations in the coagulation system, which poses a risk to patients following PCI. In this study, Penela and colleagues present retrospective data on patients surviving cardiac arrest treated with THT at their hospital.

Over a 2-year period, 28 patients surviving out-of-hospital cardiac arrest with initial ventricular fibrillation were treated with THT. They administered saline at 4° Celsius, 30 mL/kg over 30 minutes starting in the emergency room. Once in the intensive care unit, they used the Arctic Sun device to maintain body temperature at 33° for 24 hours, followed by slow rewarming. Coronary angiography was performed in 18 patients (65%), of whom 15 had a final diagnosis of ACS. Ten of these patients had ST elevation myocardial infarction (STEMI) and PCI was performed in 11 patients, with a mean door-to-balloon time of 78 ± 39 minutes. All patients undergoing PCI received intravenous heparin and guideline-based antiplatelet therapy: clopidogrel 600 mg loading dose and aspirin 300-500 mg loading dose followed by standard maintenance regimens. Definite stent thrombosis occurred in five patients (31.2%); acute in one patient and subacute in four patients. Four of these occurred in bare-metal stents, and all occurred in patients who had originally presented with ST elevation. Four were diagnosed angiographically and one at autopsy. The mean time from primary PCI to thrombotic event was 174 ± 146 hours (range, 8-376 hours). In addition, two patients had a thrombotic complication that was not related to PCI: one patient had a pulmonary embolism and another patient had a deep vein thrombosis, both occurring before discharge. There were no bleeding complications. During the same period, the authors’ institution performed 2737 PCI procedures, of which 42% were primary PCI. The rate of definite stent thrombosis during that period was 0.44% in patients without THT and 0.7% in patients undergoing primary PCI. The authors conclude that THT is associated with a disturbingly high number of cases of stent thrombosis, despite guideline-based antithrombotic therapy, and that new research is needed to determine the cause of these episodes, as well as the optimal antithrombotic therapy in these patients.

Commentary

Patients suffering out-of-hospital cardiac arrest have a poor prognosis. THT has been shown to improve their neurologic prognosis, but a definite effect on the heart has not been shown. In this study, Penela and colleagues present a single-center, retrospective experience of patients who present after surviving out-of-hospital cardiac arrest and an initial shockable rhythm. Despite being a high-volume PCI center, the numbers are small. The actual number of patients having definite stent thrombosis was only five. We are not told how many patients fulfilled criteria for probable or possible stent thrombosis. However, despite the small absolute numbers, the proportion of patients after THT suffering stent thrombosis compared to primary PCI patients not treated with THT is alarming (31% vs 0.7%). The stent thrombosis cases occurred from 8 hours to 16 days post PCI. The cause is not likely to be a mechanical or technical problem in such a high-volume center whose stent thrombosis rates in other cases are consistent with prior published data. The authors suggest that this could be due to an effect of hypothermia on platelet aggregation, which may explain the early stent thrombosis. Why, then, would stent thrombosis occur up to 16 days later when all the platelets exposed to THT are likely to have been replaced by normal turnover (circulating life of platelets is around 1 week)? That is not so easily explained. Perhaps there is an effect on the fibrinolytic or thrombosis pathways independent of the platelet. This may also explain the occurrence of deep venous thrombosis and pulmonary embolism in two patients. Regardless of the cause, the signal from this study suggests that these patients are at very high risk of stent thrombosis. These data should be validated in larger cohorts. Until that time, we should be vigilant for stent thrombosis and make every attempt to use meticulous procedural technique and optimal anticoagulant and anti-platelet therapy in these patients.