High Residual Platelet Reactivity Predicts Future Cardiovascular Events

With the increased use of platelet function testing, high residual platelet reactivity (HRPR) has been found to associate with a high risk of ischaemic events following percutaenous coronary intervention (PCI).  However, few data exist for patients with acute coronary syndromes (ACS).  To this end, the Responsiveness to Clopidogrel and Stent Thrombosis 2-ACS (RECLOSE 2-ACS) study investigated the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in ACS patients undergoing an invasive procedure, even when the long-term antithrombotic treatment was adjusted according to the results of the platelet function tests.

The study included 1789 consecutive ACS patients recruited over a four year period, 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 per day of aspirin and 75 mg per day of clopidogrel for at least 6 months. Patients with HRPR as assessed by an adenosine diphosphate test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg per day) or switched to ticlopidine (500-1000 mg per day) under adenosine diphosphate test guidance.  The primary end point was a composite of cardiac death,myocardial infarction, any urgent coronary revascularization, and stroke at 2-year followup. Secondary end points were stent thrombosis and each component of the primary end point.

The primary end point event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; P=.003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs 2.9% [44/1525]; P=.01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; P=.02) and with cardiac mortality (hazard ratio, 1.81; P=.006).
In patients undergoing invasive treatment for an acute coronary syndrome, HRPR status was associated with a significantly increased risk of ischaemic events both in the short- and long-term, even after adjustment of antithrombotic therapy.
  • Parodi G, Marcucci R, Valenti R, et al.  High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI.  JAMA 2011; 306: 1215-1223.