Risk Stratification Using Platelet Aggregation in Stable CAD

High platelet aggregation levels did not predict cardiovascular events in patients with stable coronary artery disease (CAD), according to a study published in the Journal of the American Heart Association.

Researchers from Aarhus University Hospital in Denmark included 900 patients with stable CAD who had either previous myocardial infarction (MI), type 2 diabetes, or both. Patients received single antithrombotic therapy with aspirin (75 mg/d). The VerifyNow® Aspirin Assay (Accriva Diagnostics; San Diego, California) and Multiplate® Analyzer (Roche Diagnostics International; Rotkreuz, Switzerland; agonists: arachidonic acid and collagen) measured platelet aggregation 1 hour after aspirin intake. Serum thromboxane B₂ levels confirmed aspirin adherence.

The primary end point was a composite of nonfatal MI, ischemic stroke, and cardiovascular death. Secondary end points included a composite of nonfatal MI, ischemic stroke, stent thrombosis, and all-cause death and the single end points. Patients were followed for a median of 3.1 years. Platelet aggregation results were divided into quartiles: highest aggregation (first) to lowest aggregation (fourth).

Patients with high platelet aggregation levels did not experience the primary end point more frequently as assessed by VerifyNow (hazard ratio [HR], 0.5; 95% CI, 0.3-1.1; P =.08) or Multiplate using arachidonic acid (HR, 1.0; 95% CI, 0.5-2.1; P =.92) or collagen (HR, 1.4; 95% CI, 0.7-2.8; P =.38). The total number of primary end point events recorded was 78 (8.7%).

Single secondary end points also did not occur more frequently in the fourth vs first aggregation quartile according to any of the platelet aggregation tests. However, renal insufficiency did independently predict all-cause death (HR, 3.0; 95% CI, 1.7-5.2; P <.0001) and cardiovascular death (HR, 2.6; 95% Ci, 1.1-6.0; P =.03). Stent thrombosis, ischemic stroke, and MI were not predicted by renal insufficiency. In addition, thromboxane B2 levels did not predict any of the end points, regardless of quartile.

The researchers noted that age, sex, type 2 diabetes, prior MI, smoking status, and body mass index did not have an effect on any of the end points. “This result conflicts with recent articles showing the influence of clinical risk factors on major adverse cardiovascular events in patients on dual antiplatelet therapy with aspirin and clopidogrel,” they pointed out.

Based on their findings, the researchers concluded that routine risk stratification based on platelet aggregation in patients with stable CAD treated with aspirin only is unnecessary.

Study Limitations

• The platelet aggregation levels were not assessed over time because platelet function was measured only once. 
• Platelet function may have been affected by circadian variation as the measurements were taken between 8 AM and 3 PM.
• Absorption and aspirin efficacy can vary depending on food intake, and not all patients fasted prior to blood sampling.

Reference

Larsen SB, Grove EL, Neergaard-Petersen S, Würtz M, Hvas A-M, Kristensen SD. Reduced antiplatelet effect of aspirin does not predict cardiovascular events in patients with stable coronary artery disease [published online August 5, 2017]. J Am Heart Assoc. doi:10.1161/JAHA.117.006050