title: Resistance to low-dose aspirin therapy among patients with acute coronary syndrome in relation to associated risk factors.
abstract: BACKGROUND
  A substantial proportion of patients have recurrence of vascular events despite daily intake of low-dose aspirin therapy. Therefore, different patients may require different aspirin dosages to achieve complete inhibition of platelet function.
  
  
  OBJECTIVE
  The aim of this work was to measure the response to low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non-ST-segment elevation myocardial infarction and to find out whether titrating aspirin dosage to 300 mg/day, would provide a better therapeutic response in the resistant cases. Moreover, we also aimed to study any association between aspirin non-responsiveness and atherothrombotic risk factors.
  
  
  METHODS
  The antiplatelet effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients with unstable angina or non-ST-segment elevation myocardial infarction. Platelet aggregation was measured using optical platelet aggregometry and serum thromboxane B(2) level. Aspirin resistance was defined as collagen (1 μg/mL) and adenosine diphosphate (ADP) (5 μmol/L)-induced platelet aggregation of ≥ 40% when compared with control values. Twenty healthy age- and sex-matched individuals were taken as a control group. All patients were subjected to complete medical history (risk factors, medications), thorough clinical examination, ECG, coronary angiography and laboratory investigations including: complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood glucose and glycated haemoglobin (HbA(1C) ).
  
  
  RESULTS
  Eleven of 50 patients (22%) were found to be aspirin resistant. A highly significant difference was found between the mean values of ADP, collagen-induced platelet aggregation percentage and thromboxane B(2) level after aspirin 150 mg/day when compared with the corresponding mean values after aspirin 300 mg/day among the resistant patients (66 ± 7.01%, 62 ± 4.34% and 620 ± 64.58 pg/mL, respectively, vs. 26.87 ± 2.85%, 16.5 ± 3.8% and 77 ± 11.3 pg/mL) indicating enhanced response to aspirin after escalating the dose. The presence of atherothrombotic risk factors (hypertension, smoking, family history of ischaemic heart disease and previous MI) were not statistically different between aspirin-resistant and aspirin-sensitive patients. However, there was a highly significant difference between the aspirin sensitive and the resistant patients regarding the other risk factors (diabetes mellitus and dyslipidaemia) (P < 0.01).
  
  
  CONCLUSIONS
  There is inter-individual variability in response to the antiplatelet effect of standard doses of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in resistant patients when compared to 150 mg/day. There was a significant association between aspirin resistance and atherothrombotic risk factors (diabetes, hyperlipidaemia and obesity).
authors.affiliation: Department of Clinical Pharmacy, Ain Shams University, Cairo, Egypt. miramiramira_5@yahoo.com
authors.forename: M M
authors.initials: MM
authors.lastname: Salama
authors.forename: A-R Mohamed
authors.initials: AR
authors.lastname: Morad
authors.forename: M A
authors.initials: MA
authors.lastname: Saleh
authors.forename: N A
authors.initials: NA
authors.lastname: Sabri
authors.forename: M M
authors.initials: MM
authors.lastname: Zaki
authors.forename: L A
authors.initials: LA
authors.lastname: ElSafady
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000244:Adenosine Diphosphate / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D011446:Prospective Studies; D012307:Risk Factors; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin