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Relationship between Adverse Gastric Reactions and the Timing of Enteric-Coated Aspirin Administration

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Abstract

Objective

This study aimed to elucidate the association between the adverse gastric effects of enteric-coated aspirin and the timing of its administration.

Methods

The study population comprised 572 patients (age range 45–84 years) admitted to Huaiyin Hospital between August 2012 and October 2014. Patients were administered a 100 mg enteric-coated aspirin tablet once daily: before a meal (30 min before a meal), during a meal, after a meal (30 min after a meal), or before sleep, and all patients were followed up for 6–9 months to observe for adverse gastric reactions and other side effects. Gastroscopy was performed if indicated by the patient’s condition after obtaining due consent. In addition, release tests for an enteric-coated aspirin tablet were conducted using the chromatography method.

Results

Enteric-coated aspirin tablets released completely, with a release rate of >99 % under 20–120 min at pH > 5.5. Furthermore, the number of patients with recurring adverse stomach reactions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p < 0.05). No significant between-group differences were observed with respect to damage to other organs. Similarly, the number of patients with gastric lesions was significantly lower in the before-meal and before-sleep groups than that observed in the during-meal and after-meal groups (p < 0.05).

Conclusions

The optimal time for once-daily administration of low-dose enteric-coated aspirin tablets was before a meal or before sleep owing to the increase in pH level during and after meals.

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References

  1. VanWormer JJ, Greenlee RT, McBride PE, Peppard PE, Malecki KC, Che J, et al. Aspirin for primary prevention of CVD: are the right people using it? J Fam Pract. 2012;61:525–32.

    PubMed  Google Scholar 

  2. Wu IC, Hsieh HM, Yu FJ, Wu MC, Wu TS, Wu MT. A long-term risk-benefit analysis of low-dose aspirin in primary prevention. Eur J Clin Invest. 2016;46:130–40.

    Article  CAS  PubMed  Google Scholar 

  3. Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Kandala NB, et al. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess. 2013;17:1–253.

    Google Scholar 

  4. Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Ngianga-Bakwin K, et al. Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PLoS One. 2013;8:e81970.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;136:161–72.

    Article  CAS  PubMed  Google Scholar 

  6. Hennekens CH, Dalen JE. Aspirin in the primary prevention of cardiovascular disease: current knowledge and future research needs. Trends Cardiovasc Med. 2014;24:360–6.

    Article  PubMed  Google Scholar 

  7. Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet. 2009;373:1849–60.

  8. Kawasaki K, Kurahara K, Yanai S, Kochi S, Fuchigami T, Matsumoto T. Low-dose aspirin and non-steroidal anti-inflammatory drugs increase the risk of bleeding in patients with gastroduodenal ulcer. Dig Dis Sci. 2015;60:1010–5.

    Article  CAS  PubMed  Google Scholar 

  9. Sugano K, Matsumoto Y, Itabashi T, Abe S, Sakaki N, Ashida K, et al. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial. J Gastroenterol. 2011;46:724–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kawamura N, Ito Y, Sasaki M, Iida A, Mizuno M, Ogasawara N, et al. Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers. BMC Res Notes. 2013;6:455.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet. 2009;374:1449–61.

    Article  CAS  PubMed  Google Scholar 

  12. Iwakiri R, Higuchi K, Kato M, Fujishiro M, Kinoshita Y, Watanabe T, et al. Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin. Aliment Pharmacol Ther. 2014;40:780–95.

    Article  CAS  PubMed  Google Scholar 

  13. Uemura N, Sugano K, Hiraishi H, Shimada K, Goto S, Uchiyama S, et al. Risk factor profiles, drug usage, and prevalence of aspirin-associated gastroduodenal injuries among high-risk cardiovascular Japanese patients: the results from the MAGIC study. J Gastroenterol. 2014;49:814–24.

    Article  PubMed  Google Scholar 

  14. Sakamoto C, Sugano K, Ota S, Takahashi S, Yoshida Y, Tsukui T, et al. Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan. Eur J Clin Pharmacol. 2006;62:765–72.

    Article  CAS  PubMed  Google Scholar 

  15. Nakashima S, Arai S, Mizuno Y, Yoshino K, Ando S, Nakamura Y, et al. A clinical study of Japanese patients with ulcer induced by low-dose aspirin and other non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2005;21:60–6.

    Article  CAS  PubMed  Google Scholar 

  16. Mo C, Sun G, Lu ML, Zhang L, Wang YZ, Sun X, et al. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries. World J Gastroenterol. 2015;21:5382–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sugano K. Prevention of upper gastrointestinal ulcer and complications in low-dose aspirin users. Curr Pharm Des. 2015;21:5082–8.

    Article  CAS  PubMed  Google Scholar 

  18. Nagata N, Niikura R, Aoki T, Sakurai T, Moriyasu S, Shimbo T, et al. Effect of proton-pump inhibitors on the risk of lower gastrointestinal bleeding associated with NSAIDs, aspirin, clopidogrel, and warfarin. J Gastroenterol. 2015;50:1079–86.

    Article  CAS  PubMed  Google Scholar 

  19. Mashita Y, Taniguchi M, Yokota A, Tanaka A, Takeuchi K. Oral but not parenteral aspirin upregulates COX-2 expression in rat stomachs. a relationship between COX-2 expression and PG deficiency. Digestion. 2006;73(2–3):124–32.

    Article  CAS  PubMed  Google Scholar 

  20. Gudis K, Sakamoto C. The role of cyclooxygenase in gastric mucosal protection. Dig Dis Sci. 2005;50(Suppl 1):S16–23.

    Article  CAS  PubMed  Google Scholar 

  21. Brzozowski T, Konturek PC, Sliwowski Z, Kwiecień S, Drozdowicz D, Pawlik M, et al. Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals. J Physiol Pharmacol. 2006;57(Suppl 3):67–79.

    PubMed  Google Scholar 

  22. Iwamoto J, Saito Y, Honda A, Matsuzaki Y. Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy. World J Gastroenterol. 2013;19(11):1673–82.

  23. Venerito M, Treiber G, Wex T, Kuester D, Roessner A, Di Mario F, et al. Effects of low-dose aspirin on gastric erosions, cyclooxygenase expression and mucosal prostaglandin-E2 do not depend on Helicobacter pylori infection. Aliment Pharmacol Ther. 2006;23(8):1225–33.

    Article  CAS  PubMed  Google Scholar 

  24. Venerito M, Treiber G, Wex T, Kuester D, Roessner A, Mönkemüller K, et al. Short-term/low-dose aspirin-induced duodenal erosions are not dependent on Helicobacter pylori infection, cyclooxygenase expression and prostaglandin E2 levels. Scand J Gastroenterol. 2008;43(7):801–9.

    Article  CAS  PubMed  Google Scholar 

  25. Wang RQ, Xu SC. Changes of endogastric pH in 24 hours in patients with duodenal ulcer. Henan J Diagn Ther. 2002;16:249–50.

    Google Scholar 

  26. ASGE Standards of Practice Committee, Early DS, Ben-Menachem T, et al. Appropriate use of GI endoscopy. Gastrointest Endosc. 2012;75(6):1127–31.

    Article  Google Scholar 

  27. Nakanishi T, Tamai I. Interaction of drug or food with drug transporters in intestine and liver. Curr Drug Metab. 2015;16:753–64.

    Article  CAS  PubMed  Google Scholar 

  28. Xu CH, Cheng G, Liu Y, Tian Y, Yan J, Zou MJ. Effect of the timing of food intake on the absorption and bioavailability of carbamazepine immediate-release tablets in beagle dogs. Biopharm Drug Dispos. 2012;33:30–8.

    Article  PubMed  Google Scholar 

  29. Ying XL. Oral administration of enteric-coated tablets of aspirin are two days comparison gastric responses. Chin Med Mod Distance Educ China. 2010;9:230.

    Google Scholar 

  30. Lian XF, Xiang DC. Influence of administration time of enteric-coated tablets of aspirin on gastric adverse effects. Chin J Coal Ind Med. 2005;8:457–8.

    Google Scholar 

  31. Maree AO, Curtin RJ, Dooley M, Conroy RM, Crean P, Cox D, et al. Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. J Am Coll Cardiol. 2005;46:1258–63.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Cardiology, Huaiyin Hospital, No.38, Beijing West Road, Huaiyin District, Huai’an, 223300, Jiangsu Province, China

    Weijun Guo, Wenlin Lu, Yujun Xu, Qin Wei & Qingyun Zhao

  2. Department of Cardiology, Jiangsu Province People’s Hospital, Nanjing, China

    Liansheng Wang

Authors
  1. Weijun Guo
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  2. Wenlin Lu
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  3. Yujun Xu
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  4. Liansheng Wang
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  5. Qin Wei
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  6. Qingyun Zhao
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Corresponding author

Correspondence to Weijun Guo.

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Conflict of interest

Weijun Guo, Wenlin Lu, Yujun Xu, Liansheng Wang, Qin Wei and Qingyun Zhao have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee at Huaiyin Hospital (Number HYYY201207080) and the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all patients prior to their enrollment in the study.

Funding

This study was funded by grants from the Huaiyin Hospital.

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Guo, W., Lu, W., Xu, Y. et al. Relationship between Adverse Gastric Reactions and the Timing of Enteric-Coated Aspirin Administration. Clin Drug Investig 37, 187–193 (2017). https://doi.org/10.1007/s40261-016-0474-z

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  • DOI: https://doi.org/10.1007/s40261-016-0474-z

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