Elsevier

International Journal of Cardiology

Volume 183, 15 March 2015, Pages 263-266
International Journal of Cardiology

Actively using clopidogrel correlates with an increased risk of acute pancreatitis in Taiwan

https://doi.org/10.1016/j.ijcard.2014.09.042Get rights and content

Highlights

  • Persons actively using clopidogrel are at an increased risk of acute pancreatitis.

  • If not actively using clopidogrel, the risk would decrease.

  • Actively using clopidogrel would markedly enhance the risk of acute pancreatitis among persons with cardiovascular disease.

Abstract

The aim of this study is to assess whether there is an association between clopidogrel use and risk of acute pancreatitis in Taiwan.

We conducted a case–control study using the database of the Taiwan National Health Insurance Program from 2000 to 2011. There were 5644 subjects aged 20–84 years with a first-time attack of acute pancreatitis as the case group and 22,576 randomly selected sex-matched and age-matched subjects without acute pancreatitis as the control group. We defined clopidogrel use as “actively using” if the final clopidogrel prescription was filled between 0 and 7 days before the date of diagnosing acute pancreatitis, or “not actively using” if the final clopidogrel prescription was filled ≧ 8 days before the date of diagnosing acute pancreatitis. Subjects who never used clopidogrel were defined as never used. The multivariable logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute pancreatitis associated with clopidogrel use.

Comparing the subjects actively using clopidogrel to those who never used clopidogrel, the adjusted OR of acute pancreatitis was 8.46 (95%CI 5.25, 13.7). The adjusted OR decreased to 1.16 among subjects not actively using clopidogrel (95%CI 0.95, 1.43).

Persons actively using clopidogrel are at an increased risk of acute pancreatitis. Further studies are necessary to prove the causal relationship.

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)

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