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Thromb Haemost 2011; 105(02): 336-344
DOI: 10.1160/TH10-02-0082
Platelets and Blood Cells
Schattauer GmbH

24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease

Patrick Henry
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Adeline Vermillet
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Bernadette Boval
2   Angio-hematology, Lariboisiere hospital, AP-HP and University Paris VIIDiderot, Paris, France
,
Carine Guyetand
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Thibaut Petroni
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Jean-Guillaume Dillinger
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Georgios Sideris
1   Cardiology & INSERM U942, Lariboisiere hospital, AP-HP and University Paris VII-Diderot, Paris, France
,
Claire Bal dit Sollier
2   Angio-hematology, Lariboisiere hospital, AP-HP and University Paris VIIDiderot, Paris, France
,
Ludovic Drouet
2   Angio-hematology, Lariboisiere hospital, AP-HP and University Paris VIIDiderot, Paris, France
› Author Affiliations Financial support: This work was supported by the Institute of Blood and Vessels (account n°LTA/003).
Further Information

Publication History

Received: 01 February 2010

Accepted after major revision: 22 October 2010

Publication Date:
25 November 2017 (online)

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Summary

Aspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h –24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h – 4% of patients, 6 h – 4%, 12 h – 11%, 16 h – 16%, 20 h – 19% and 24 h – 28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75–100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance» at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.

Keywords

Platelet aggregation - aspirin - aspirin resistance - coronary artery disease
 

  • References

  • 1 Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
    CrossrefPubMedGoogle Scholar
  • 2 Campbell CL, Smyth S, Montalescot G. et al. Aspirin dose for the prevention of cardiovascular disease: a systematic review. J Am Med Assoc 2007; 297: 2018-2024.
    CrossrefPubMedGoogle Scholar
  • 3 Patrono C, Baigent C, Hirsh J. et al. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 199S-233S.
    CrossrefPubMedGoogle Scholar
  • 4 Cipollone F, Ciabattoni G, Patrignani P. et al. Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina. Circulation 2000; 102: 1007-1013.
    CrossrefPubMedGoogle Scholar
  • 5 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
    CrossrefPubMedGoogle Scholar
  • 6 Snoep JD, Hovens MM, Eikenboom JC. et al. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J 2007; 154: 221-231.
    CrossrefPubMedGoogle Scholar
  • 7 Krasopoulos G, Brister SJ, Beattie WS. et al. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. Br Med J 2008; 336: 195-198.
    CrossrefPubMedGoogle Scholar
  • 8 McKee SA, Sane DC, Deliargyris EN. Aspirin resistance in cardiovascular disease: a review of prevalence, mechanisms, and clinical significance. Thromb Haemost 2002; 88: 711-715.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Mason PJ, Jacobs AK, Freedman JE. Aspirin resistance and atherothrombotic disease. J Am Coll Cardiol 2005; 46: 986-993.
    CrossrefPubMedGoogle Scholar
  • 10 Lordkipanidze M, Pharand C, Schampaert E. et al. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007; 28: 1702-1708.
    CrossrefPubMedGoogle Scholar
  • 11 Topol EJ, Easton D, Harrington RA. et al. Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation 2003; 108: 399-406.
    CrossrefPubMedGoogle Scholar
  • 12 Quinn MJ, Aronow HD, Califf RM. et al. Aspirin dose and six-month outcome after an acute coronary syndrome. J Am Coll Cardiol 2004; 43: 972-978.
    CrossrefPubMedGoogle Scholar
  • 13 Lee PY, Chen WH, Ng W. et al. Low-dose aspirin increases aspirin resistance in patients with coronary artery disease. Am J Med 2005; 118: 723-727.
    CrossrefPubMedGoogle Scholar
  • 14 Patrono C, Ciabattoni G, Patrignani P. et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 1985; 72: 1177-1184.
    CrossrefPubMedGoogle Scholar
  • 15 Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N Engl J Med 1984; 311: 1206-1211.
    CrossrefPubMedGoogle Scholar
  • 16 Brantmark B, Wahlin-Boll E, Melander A. Bioavailability of acetylsalicylic acid and salicylic acid from rapid-and slow-release formulations, and in combination with dipyridamol. Eur J Clin Pharmacol 1982; 22: 309-314.
    PubMedGoogle Scholar
  • 17 Awtry EH, Loscalzo J. Aspirin. Circulation 2000; 101: 1206-1218.
    CrossrefPubMedGoogle Scholar
  • 18 Evangelista V, Manarini S, Di Santo A. et al. De novo synthesis of cyclooxygenase-1 counteracts the suppression of platelet thromboxane biosynthesis by aspirin. Circ Res 2006; 98: 593-595.
    CrossrefPubMedGoogle Scholar
  • 19 Sonksen JR, Kong KL, Holder R. Magnitude and time course of impaired primary haemostasis after stopping chronic low and medium dose aspirin in healthy volunteers. Br J Anaesth 1999; 82: 360-365.
    CrossrefPubMedGoogle Scholar
  • 20 Watala C, Golanski J, Pluta J. et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Thromb Res 2004; 113: 101-113.
    CrossrefPubMedGoogle Scholar
  • 21 Lucas AR, Korol R, Pepine CJ. Inflammation in atherosclerosis: some thoughts about acute coronary syndromes. Circulation 2006; 113: e728-732.
    CrossrefPubMedGoogle Scholar
  • 22 Montalescot G, Sideris G, Meuleman C. et al. A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006; 48: 931-938.
    CrossrefPubMedGoogle Scholar
  • 23 Patrono C, Ciabattoni G, Pinca E. et al. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res 1980; 17: 317-327.
    CrossrefPubMedGoogle Scholar
  • 24 Heidemann DR, Schulenberg ES, Smith WH. Determination of aspirin and salicylic acid by reverse-phase liquid chromatography. J Assoc Off Anal Chem 1987; 70: 964-966.
    PubMedGoogle Scholar
  • 25 Angiolillo DJ, Fernandez-Ortiz A, Bernardo E. et al. Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention. Am J Cardiol 2006; 97: 38-43.
    CrossrefPubMedGoogle Scholar
  • 26 Cotter G, Shemesh E, Zehavi M. et al. Lack of aspirin effect: aspirin resistance or resistance to taking aspirin?. Am Heart J. 2004; 147: 293-300.
    CrossrefPubMedGoogle Scholar
  • 27 Valles J, Santos MT, Fuset MP. et al. Partial inhibition of platelet thromboxane A2 synthesis by aspirin is associated with myonecrosis in patients with ST-segment elevation myocardial infarction. Am J Cardiol 2007; 99: 19-25.
    CrossrefPubMedGoogle Scholar
  • 28 Di Minno G, Silver MJ, Murphy S. Monitoring the entry of new platelets into the circulation after ingestion of aspirin. Blood 1983; 61: 1081-1085.
    PubMedGoogle Scholar
  • 29 Cerletti C, Dell’Elba G, Manarini S. et al. Pharmacokinetic and pharmacodynamic differences between two low dosages of aspirin may affect therapeutic outcomes. Clin Pharmacokinet 2003; 42: 1059-1070.
    CrossrefPubMedGoogle Scholar
  • 30 Perneby C, Wallen NH, Rooney C. et al. Dose- and time-dependent antiplatelet effects of aspirin. Thromb Haemost 2006; 95: 652-658.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Lordkipanidze M, Pharand C, Schampaert E. et al. Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease. Int J Cardiol. 2010 prepub online.
    PubMedGoogle Scholar
  • 32 Schwartz KA, Schwartz DE, Barber K. et al. Non-compliance is the predominant cause of aspirin resistance in chronic coronary arterial disease patients. J Transl Med 2008; 6: 46.
    CrossrefPubMedGoogle Scholar
  • 33 Cuisset T, Frere C, Quilici J. et al. Aspirin noncompliance is the major cause of “aspirin resistance” in patients undergoing coronary stenting. Am Heart J 2009; 157: 889-893.
    CrossrefPubMedGoogle Scholar
  • 34 Wurtz M, Grove EL, Kristensen SD. et al. The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease. Heart 96: 368-371.
    PubMedGoogle Scholar
  • 35 Catella-Lawson F, Reilly MP, Kapoor SC. et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001; 345: 1809-1817.
    CrossrefPubMedGoogle Scholar
  • 36 Crescente M, Cerletti C, de Gaetano G. Gallic acid, a dietary polyphenolic component, blunts the inhibition of platelet COX-1 by aspirin: preliminary in-vitro findings. Thromb Haemost 2007; 97: 1054-1056.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Halushka MK, Walker LP, Halushka PV. Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther 2003; 73: 122-130.
    CrossrefPubMedGoogle Scholar
  • 38 Macchi L, Christiaens L, Brabant S. et al. Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/ IIa) and C-5T Kozak (GP Ibalpha) polymorphisms. J Am Coll Cardiol 2003; 42: 1115-1119.
    CrossrefPubMedGoogle Scholar
  • 39 Lordkipanidze M, Diodati JG, Turgeon J. et al. Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin. Int J Cardiol 2010; 143: 43-50.
    CrossrefPubMedGoogle Scholar
  • 40 Patrono C, Rocca B. Drug insight: aspirin resistance--fact or fashion?. Nat Clin Pract Cardiovasc Med 2007; 4: 42-50.
    CrossrefPubMedGoogle Scholar
  • 41 FitzGerald GA, Brash AR, Oates JA. et al. Endogenous prostacyclin biosynthesis and platelet function during selective inhibition of thromboxane synthase in man. J Clin Invest 1983; 72: 1336-1343.
    CrossrefPubMedGoogle Scholar
  • 42 Dragani A, Pascale S, Recchiuti A. et al. The contribution of cyclooxygenase-1 and –2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy. Blood 2010; 115: 1054-1061.
    CrossrefPubMedGoogle Scholar
  • 43 Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res 1993; 71: 397-403.
    CrossrefPubMedGoogle Scholar
  • 44 Helgason CM, Bolin KM, Hoff JA. et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994; 25: 2331-2336.
    CrossrefPubMedGoogle Scholar
  • 45 Mehta SS, Silver RJ, Aaronson A. et al. Comparison of aspirin resistance in type 1 versus type 2 diabetes mellitus. Am J Cardiol 2006; 97: 567-570.
    CrossrefPubMedGoogle Scholar
  • 46 Grove EL, Hvas AM, Johnsen HL. et al. A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease. Thromb Haemost 2010; 103: 1245-1253.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Gurbel PA, Becker RC, Mann KG. et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007; 50: 1822-1834.
    CrossrefPubMedGoogle Scholar
  • 48 Gurbel PA, Bliden KP, DiChiara J. et al. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 2007; 115: 3156-3164.
    CrossrefPubMedGoogle Scholar
  • 49 Pulcinelli FM, Riondino S, Celestini A. et al. Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin. J Thromb Haemost 2005; 3: 2784-2789.
    CrossrefPubMedGoogle Scholar