BMJ  2006;333:726 (7 October), doi:10.1136/bmj.38947.697558.AE (published 19 September 2006)

Research

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study

Jesper Hallas, professor1, Michael Dall, registrar3, Alin Andries, registrar4, Birthe Søgaard Andersen, senior registrar4, Claus Aalykke, senior registrar3, Jane Møller Hansen, senior physician3, Morten Andersen, senior researcher2, Annmarie Touborg Lassen, senior registrar5

1 Department of Clinical Pharmacology, IST, Syddansk Universitet, 5000 Odense, Denmark, 2 Research Unit of General Practice, Syddansk Universitet, 3 Department of Medical Gastroenterology, Odense University Hospital, Odense, 4 Department of Cardiology, Odense University Hospital, 5 Department of Infectious Medicine, Odense University Hospital

Correspondence to: J Hallas jhallas{at}health.sdu.dk

Abstract

Objectives To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population.

Design Population based case-control study.

Setting Funen County, Denmark (population 470 000).

Subjects 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57 720 age and sex matched controls.

Main outcome measure Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment.

Results Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population.

Conclusion Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.


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