Advanced age and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

J Thromb Haemost. 2016 Jan;14(1):57-64. doi: 10.1111/jth.13177. Epub 2015 Dec 29.

Abstract

ESSENTIALS: Dual antiplatelet therapy (DAPT) in elderly patients requires balancing bleedings and thrombosis. Impact of age on high residual on-treatment platelet reactivity (HRPR) on DAPT was studied. A reduced effectiveness of adenosine diphosphate antagonists was observed over 70 years of age. The occurrence of HRPR was increased among elderly patients with both clopidogrel and ticagrelor.

Background: The aim of the present study was to evaluate the impact of age on platelet function and the occurrence of high residual on-treatment platelet reactivity (HRPR) in patients treated with dual antiplatelet therapy (DAPT) using acetylsalicilic acid (ASA) and clopidogrel or ticagrelor.

Methods: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values > 417 AU*min (for ADP antagonists). Elderly patients were defined as those aged ≥ 70 years.

Results: Among 494 patients on DAPT, 224 (45.3%) were ≥ 70 years old. ADP-mediated platelet aggregation increased with decades of age (279.3 ± 148.6 vs. 319.6 ± 171.1 vs. 347.3 ± 190.1 vs. 345.7 ± 169.2), whereas no difference was observed for ASA response. A reduced effectiveness of ADP antagonists was observed among elderly patients; in fact, among the 117 patients displaying HRPR (23.7%), a higher prevalence was observed among patients over 70 years old (30.4% vs. 18.1%; adjusted odds ratio (OR) [95% confidence interval (CI)] = 2.19 [1.29-3.71]). Similar results were obtained among the 266 clopidogrel-treated patients (38.5% vs. 27.9%; adjusted OR [95% CI] = 2.91 [1.46-5.8]) and in the 228 patients receiving ticagrelor (19.1% vs. 8.1%; adjusted OR [95% CI] = 2.55 [1.02-8.59]).

Conclusion: In patients receiving dual antiplatelet therapy, advanced age is independently associated with a reduced effectiveness of ADP antagonists and a higher rate of HRPR with both clopidogrel and ticagrelor.

Keywords: aging; antithrombotic agents; coronary artery disease; pharmacology; platelet aggregation inhibitors.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Adenosine Diphosphate / metabolism
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aspirin / blood
  • Blood Platelets / drug effects
  • Clopidogrel
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Patient Discharge
  • Percutaneous Coronary Intervention
  • Platelet Activation
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prevalence
  • Thrombosis / drug therapy
  • Ticagrelor
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors

Substances

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