Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers

Department of Clinical Pharmacology, Royal College of Surgeons, 123 St Stephens Green, Dublin 2, Ireland.
Stroke (Impact Factor: 5.72). 09/2006; 37(8):2153-8. DOI: 10.1161/
Source: PubMed

ABSTRACT Aspirin resistance may be relatively common and associated with adverse outcome. Meta-analysis has clearly shown that 75 mg plain aspirin is the lowest effective dose; however, it is not known whether the recent increased use of enteric-coated aspirin could account for aspirin resistance. This study was designed to determine whether enteric-coated aspirin is as effective as plain aspirin in healthy volunteers.
Seventy-one healthy volunteers were enrolled in 3 separate bioequivalence studies. Using a crossover design, each volunteer took 2 different aspirin preparations. Five aspirin preparations were evaluated, 3 different enteric-coated 75-mg aspirins, dispersible aspirin 75 mg and asasantin (25-mg standard release aspirin plus 200-mg modified-release dipyridamole given twice daily). Serum thromboxane (TX) B2 levels and arachidonic acid-induced platelet aggregation were measured before and after 14 days of treatment.
All other aspirin preparations tested were inferior to dispersible aspirin (P<0.001) in their effect on serum TXB(2) level. Treatment failure (<95% inhibition serum TXB2 formation) occurred in 14 subjects, none of whom were taking dispersible aspirin. Mean weight for those demonstrating treatment failure was greater than those with complete TXB2 (>99%) inhibition (P<0.001). Using logistic regression analysis an 80-kg subject had a 20% probability of treatment failure. Asasantin was the most potent preparation in terms of inhibition of platelet aggregation.
Equivalent doses of the enteric-coated aspirin were not as effective as plain aspirin. Lower bioavailability of these preparations and poor absorption from the higher pH environment of the small intestine may result in inadequate platelet inhibition, particularly in heavier subjects.

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    • "Aspirin use before stroke was more common in the very old population , in particular in the women of this group, and was associated with the incidence of AIS. Other studies support that regular aspirin use may be associated with increased rates of ischemic stroke in low-risk populations [23], with increased systolic blood pressure, and with antagonization of the effect of certain antihypertensive drugs [24] [25]. The thrombogenic effects of aspirin have been demonstrated experimentally, particularly at high doses, and possibly relate to inhibition of endothelial-derived prostacyclin synthesis or, in some patients, to an increase in platelet adhesiveness [26]. "
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    ABSTRACT: Acute ischemic stroke (AIS) is influenced by gender, age, and the brain site affected. Better characterization of AIS is necessary for improving guidelines, prevention, and destination of resources. Demographics, prestroke conditions, etiology, subtypes, specific hospital outcome, clinical and laboratory parameters, and mortality rates were prospectively registered in 105 southern Italian patients. AIS became more frequent in women than in men after age 65years. Cryptogenic AIS decreased with age independently of sex and lesion site. Cerebellum-brainstem stroke was more prevalent in men, whereas anterior AIS was more frequent in women. There were no overall differences in 6- and 12-month survival rates based on site or sex; however, mortality rates were high after age 80years. Chronic kidney disease was more frequent in patients with cerebellum-brainstem stroke, and its prevalence increased significantly with age independently of sex. Association of AIS with arterial hypertension, diabetes, and previous myocardial infarction increased with age, whereas that with active smoking decreased with age, independently of sex and site. Specific AIS etiology and blood characteristics associated independently to the youngest and oldest AIS patients, respectively. Chronic kidney disease was a specific predictor of cerebellum-brainstem AIS. AIS mortality showed peculiar association with the oldest patients.
    Journal of the neurological sciences 01/2014; 339(1-2). DOI:10.1016/j.jns.2014.01.014 · 2.47 Impact Factor
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    • "This observation supports the hypothesis that greater platelet turnover may account for an impaired response to aspirin, either because of an increased number of circulating non-aspirinated platelets or an increased number of platelets that retain the ability to synthesize thromboxane [17]. Patient characteristics (body weight, diabetes, hyperlipidemia, hypertension and aspirin formulation (enteric-coated vs. non-enteric coated) have also been associated with aspirin low response [18] [19] [20] [21]. We found complete platelet suppression in all patients before surgery, but cannot exclude the possibility that differences in baseline characteristics between aspirin low and normal response groups were determinants of postoperative aspirin response. "
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    ABSTRACT: Variability in platelet response to aspirin has been reported in patients undergoing cardiac surgery but has rarely been described in other operative settings and its mechanism remains uncertain. We performed a prospective cohort study to investigate the variability in platelet response to aspirin and to explore its mechanism in patients undergoing major orthopedic surgery. Twelve aspirin-treated patients undergoing elective hip or knee replacement were recruited. Once-daily aspirin was continued throughout the perioperative period. We measured platelet function using light transmission aggregation (LTA) in response to arachidonic acid (PL(AA)) and serum thromboxane B(2) (TXB(2)) at baseline (before surgery) as well as on days 1, 2, 3, 4, 5, 6, and 8 after surgery. We defined aspirin low response as a PL(AA)>20%. Six patients exhibited aspirin low response, which typically started on post-operative days 3 or 4; the remaining 6 patients had normal response to aspirin. Compared to aspirin responders, patients with aspirin low response showed significantly higher serum TXB(2) levels, a more pronounced early decrease in platelet count, and a significantly more rapid recovery of the platelet count after surgery. Aspirin response variability occurred in patients after major orthopedic surgery, with one-half of the patients in our study exhibiting post-operative aspirin low response. Increased platelet turnover might be a contributor to aspirin response variability after orthopedic surgery.
    Thrombosis Research 05/2012; 130(2):216-20. DOI:10.1016/j.thromres.2012.04.006 · 2.45 Impact Factor
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    • "Abbreviations: ASA: aspirin; EC: enteric coated. This table is modified from [26]. "
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    ABSTRACT: The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term "aspirin resistance" was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations.
    01/2012; 2012(25):376721. DOI:10.1155/2012/376721
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