Journal of General Internal Medicine

, Volume 28, Issue 2, pp 216–222

Gastrointestinal Events with Clopidogrel: A Nationwide Population-Based Cohort Study

  • Erik Lerkevang Grove
  • Morten Würtz
  • Peter Schwarz
  • Niklas Rye Jørgensen
  • Peter Vestergaard
Original Research

DOI: 10.1007/s11606-012-2208-0

Cite this article as:
Grove, E.L., Würtz, M., Schwarz, P. et al. J GEN INTERN MED (2013) 28: 216. doi:10.1007/s11606-012-2208-0

ABSTRACT

BACKGROUND

Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events.

OBJECTIVE

We aimed to investigate the risk of adverse GI events in patients treated with clopidogrel.

DESIGN

A nationwide population-based cohort study based on linkage of three administrative registries in Denmark.

PARTICIPANTS

All individuals who redeemed at least one prescription of clopidogrel from 1996 to 2008 were included as exposed subjects (n = 77,503). For each exposed subject, three matched controls were randomly selected from the background population (n = 232,510).

ANALYSES

Follow-up began on January 1, 1996, and was censored on December 31, 2007, or if patients emigrated or died. The study endpoint was the occurrence of any gastritis, GI ulcer or bleeding. Analyses were adjusted for comorbidity and medication.

RESULTS

Regardless of dose, adjusted odds ratios associating clopidogrel use with the study endpoint were statistically significant and followed a dose–response pattern. The crude absolute risk of GI events were: never users: 2.2 %; <0.1 defined daily dose (DDD) of clopidogrel per day: 7.1 %; 0.1–0.39 DDD: 6.0 %; 0.4–0.79 DDD: 5.7 %; ≥0.80 DDD: 4.4 %. Adjusted odds ratios were: <0.1 DDD: 1.34, 95 % CI: 1.26–1.42; 0.1–0.39 DDD: 1.58, 95 % CI: 1.48–1.68; 0.4–0.79 DDD: 1.91, 95 % CI: 1.77–2.06; ≥0.80 DDD: 1.77, 95 % CI: 1.66–1.89, all p-values < 0.01. Depending on the dose, numbers needed to harm ranged from 58 to 33 patients receiving 12 months of clopidogrel treatment.

CONCLUSIONS

The well-known cardioprotective effect of clopidogrel must be carefully weighed against an increased risk of GI events.

KEY WORDS

clopidogrelcoronary artery diseasegastritisgastrointestinal hemorrhagestomach ulcer

Abbreviations

ADP

Adenosine diphosphate

ATC

Anatomical Therapeutical Chemical

DDD

Defined daily dose

GI

Gastrointestinal

ICD

International Classification of Diseases

Copyright information

© Society of General Internal Medicine 2012

Authors and Affiliations

  • Erik Lerkevang Grove
    • 1
  • Morten Würtz
    • 1
  • Peter Schwarz
    • 2
    • 3
  • Niklas Rye Jørgensen
    • 2
  • Peter Vestergaard
    • 4
  1. 1.Department of CardiologyAarhus University Hospital, SkejbyAarhusDenmark
  2. 2.Research Center of Aging and Osteoporosis, Departments of Medicine and DiagnosticsCopenhagen University HospitalGlostrupDenmark
  3. 3.Faculty of Health SciencesCopenhagen UniversityCopenhagenDenmark
  4. 4.Medical FacultyAalborg UniversityAalborgDenmark