Actively using clopidogrel correlates with an increased risk of acute pancreatitis in Taiwan
Introduction
Acute pancreatitis is a life-threatening condition characterized by acute inflammation of the pancreas. The epidemiological studies have revealed that gallstones and alcoholism account for 75–80% of all cases of acute pancreatitis[1], [2]. In addition, a growing body of evidence shows that many drugs have been reported to be associated with acute pancreatitis, with estimation of 2% of all cases[2], [3].
Clopidogrel is an antiplatelet agent commonly used in cardiovascular disease with significant benefits. However, bleeding is the major adverse event of clopidogrel therapy, which may frequently result in discontinuation or noncompliance with this agent[4].
So far, no case of acute pancreatitis associated with clopidogrel use has been published, whereas US Food and Drug Administration (FDA) has reported that from 1999 to 2012, 240 persons (0.36%) had acute pancreatitis among 67298 persons reporting to have adverse events when using clopidogrel[5]. Since the causal relationship between clopidogrel use and risk of acute pancreatitis remains uncertain in the US FDA report, we conducted a population-based case–control study using the database of the Taiwan National Health Insurance Program to assess whether there is an association between clopidogrel use and risk of acute pancreatitis.
Section snippets
Materials and methods
A case–control study was conducted usingthe database of the Taiwan National Health Insurance Program. Briefly speaking, the insurance program started in March 1995 and it provided outpatient, hospitalization and emergency services. Nearly, 99% of 23 million citizens living in Taiwan were covered[6]. In this program, diseases were diagnosed based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 codes). The program details can be found in previous
Characteristics of the study population
Totally, 5644 subjects with acute pancreatitis as cases and 22,576 subjects without acute pancreatitis as controls were included with equal distributions in sex and age (Table 1). The mean ages (standard deviation) were 53.59 (16.53) years in the case group and 53.13 (16.68) years in the control group. The cases tended to have higher proportions of clopidogrel use, alcoholism, biliary stone, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hepatitis B, hepatitis
Discussion
To the best of our knowledge, this is the first pharmacoepidemiological study using the population-basedclaim data to assess the association between clopidogrel use and risk of acute pancreatitis. No such data exist to be compared with. During the study period, among 5644 cases with acute pancreatitis, 260 persons (4.6%) ever used clopidogrel. We found that only persons actively using clopidogrel were at an 8.46-fold increased odds for acute pancreatitis. If not actively using clopidogrel, the
Conflict of interest statement
The authors report no relationships that could be construed as a conflict of interest.
Specific author contributions
Shih-Wei Lai: (1) substantially contributed to the conception of the article, (2) planned and conducted the article, and (3) initiated the draft of the article and critically revised the article.
Cheng-Li Lin: (1) conducted data analysis and (2) critically revised the article.
Kuan-Fu Liao: (1) planned and conducted the article, (2) participated in data interpretation, and (3) critically revised the article.
Acknowledgement
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002), China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092), NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039 -006), Tseng-Lien Lin Foundation in Taichung in Taiwan, Taiwan Brain Disease Foundation in Taipei in Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds in Japan. These funding
References (14)
Acute pancreatitis: etiology, clinical presentation, diagnosis, and therapy
Med Clin North Am
(2008)Drug-induced acute pancreatitis related to medications commonly used in gastroenterology
Eur J Intern Med
(2011)- et al.
Drug induced pancreatitis
Best Pract Res Clin Gastroenterol
(2010) - et al.
Clopidogrel–drug interactions
J Am Coll Cardiol
(2011) - et al.
The safety of clopidogrel
Expert Opin Drug Saf
(2011) eHealthMe study from FDA and social media reports. Review: could Plavix cause pancreatitis acute?
- et al.
Diabetes mellitus correlates with increased risk of pancreatic cancer: a population-based cohort study in Taiwan
J Gastroenterol Hepatol
(2012)
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