High Residual Platelet Reactivity After Clopidogrel Loading and Long-Term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI
Is high residual platelet reactivity (HRPR) an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure?
This was a prospective, observational, referral center cohort study of 1,789 consecutive patients with ACS undergoing percutaneous coronary intervention (PCI) from April 2005 to April 2009, at the Division of Cardiology of Careggi Hospital, Florence, Italy, in whom platelet reactivity was prospectively assessed by light transmittance aggregometry. All patients received 325 mg of aspirin and a loading dose of 600 mg of clopidogrel, followed by a maintenance dosage of 325 mg/d of aspirin and 75 mg/d of clopidogrel for at least 6 months. Patients with HRPR, as assessed by adenosine diphosphate (ADP) test (≥70% platelet aggregation), received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under ADP test guidance. The primary endpoint was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary endpoints were stent thrombosis and each component of the primary endpoint.
The primary endpoint event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1,525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; 95% confidence interval [CI], 1.6%-11.1%; p = 0.003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs. 2.9% [44/1,525]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; p = 0.01). By multivariable analysis, HRPR was independently associated with the primary endpoint (hazard ratio, 1.49; 95% CI, 1.08-2.05; p = 0.02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; p = 0.006).
The authors concluded that among patients receiving platelet reactivity–guided antithrombotic medication after PCI, HRPR status was significantly associated with increased risk of ischemic events at short- and long-term follow-up.
This study suggests that HRPR after clopidogrel loading is associated with increased risk of short- and long-term ischemic events, including stent thrombosis. Furthermore, normalization of the ADP test result after treatment adjustment is not associated with better outcome versus a persistent abnormal ADP test result. It remains to be seen if HRPR after 600 mg clopidogrel loading in patients undergoing PCI for ACS is a nonmodifiable risk factor for thrombotic events or if tailored therapy with use of newer, more potent antithrombotic agents such as prasugrel or ticagrelor may have a beneficial effect on clinical outcome in these patients.
Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Platelet Aggregation Inhibitors, Platelet Function Tests, Italy, Percutaneous Coronary Intervention
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