Impaired endogenous thrombolysis in acute coronary syndrome patients predicts cardiovascular death and nonfatal myocardial infarction

Abstract

Objectives: Our objective was to assess endogenous thrombolytic activity in acute coronary syndrome (ACS) patients and relate this to their likelihood of future adverse cardiovascular events. Background: Spontaneous lysis of platelet-rich thrombi is an important defense mechanism against lasting occlusion. Despite convincing evidence for the role of endogenous fibrinolysis in ACS, the prognostic value of plasma fibrinolytic markers in assessing risk is limited. We employed a novel global test which, in addition to platelet reactivity, allows assessment of endogenous thrombolytic activity to identify ACS patients who remain at risk of cardiovascular events. Methods: We used the global thrombosis test (GTT) to assess thrombotic and thrombolytic status in 300 ACS patients receiving dual-antiplatelet therapy. The test assesses the time required to form an occlusive thrombus, the occlusion time (OT), and the time to lyse this, the lysis time (LT). The end point of the study at 12 months' follow-up was the composite of death, nonfatal myocardial infarction, or stroke. Results: The OT and LT were both prolonged in ACS patients compared with normal volunteers (p < 0.001). LT ≥3,000 s occurred in 23% of ACS patients versus none of the normal subjects and was a significant and independent predictor of cardiovascular death and nonfatal myocardial infarction in a multivariate model adjusted for cardiovascular risk factors. LT ≥3,000 s was the optimal cutoff value for predicting 12-month major adverse cardiovascular events (hazard ratio [HR]: 2.52, 95% confidence interval: 1.34 to 4.71, p = 0.004) and cardiovascular death (HR: 4.2, 95% confidence interval: 1.13 to 15.62, p = 0.033). HR increased further as LT increased. No association was found between OT and the risk of major adverse cardiovascular events. Conclusions: Assessment of endogenous thrombolytic status based on the lysis of platelet-rich thrombi from native blood using the point-of-care GTT can identify ACS patients at risk of future cardiac events.