High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI

JAMA. 2011 Sep 21;306(11):1215-23. doi: 10.1001/jama.2011.1332.


Context: High residual platelet reactivity (HRPR) in patients receiving clopidogrel has been associated with high risk of ischemic events after percutaneous coronary intervention (PCI).

Objective: To test the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure and antithrombotic treatment adjusted according to the results of platelet function tests.

Design, setting, and patients: Prospective, observational, referral center cohort study of 1789 consecutive patients with ACS undergoing 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.

Interventions: 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 test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under adenosine diphosphate test guidance.

Main outcome measures: The primary end point was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary end points were stent thrombosis and each component of the primary end point.

Results: 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%; 95% CI, 1.6%-11.1%; 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]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; P = .01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; 95% CI, 1.08-2.05; P = .02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; P = .006).

Conclusion: 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.

Trial registration: clinicaltrials.gov Identifier: NCT01231035.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Adenosine Diphosphate / analysis
  • Aged
  • Angioplasty
  • Aspirin / administration & dosage
  • Clopidogrel
  • Death
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Revascularization
  • Platelet Adhesiveness / drug effects*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Prognosis
  • Prospective Studies
  • Risk
  • Stents
  • Stroke / epidemiology*
  • Thrombosis / epidemiology
  • Thrombosis / prevention & control
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*


  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT01231035