Elsevier

The American Journal of Medicine

Volume 120, Issue 4, April 2007, Pages 369.e9-369.e14
The American Journal of Medicine

AJM online
Clinical research study
Does Statin Therapy Decrease the Risk for Bleeding in Patients Who Are Receiving Warfarin?

https://doi.org/10.1016/j.amjmed.2006.06.008Get rights and content

Abstract

Purpose

Recent observations in patients with atrial fibrillation who are receiving warfarin suggest that concomitant treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) decreases the risk for bleeding.

Methods

We conducted a population-based, nested case-control study using the linked administrative databases of Ontario, Canada, to assess whether statin use decreases the risk of bleeding in warfarin users. Eligible patients were Ontario residents, age 66 years or more, with atrial fibrillation who were prescribed warfarin between April 1, 1994, and December 31, 2001. Patients were followed until hospitalization for upper gastrointestinal or intracranial bleeding, study end (March 31, 2002), discontinuation of warfarin, or death. Cases were matched to controls by age and sex. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between bleeding and statin use.

Results

We identified 79,207 warfarin users with atrial fibrillation. There were 1518 cases with an upper gastrointestinal or intracranial bleed and 15,100 matched controls without bleeding. Long-term (≥1 year) statin use was associated with a lower risk for any bleeding (OR = 0.80; 95% CI, 0.66-0.97). However, there was no association between bleeding and recent (<6 months) statin use (OR = 1.04; 95% CI, 0.74-1.48) or statin use of any duration (OR: 0.91; 95% CI, 0.77-1.07), suggesting potential confounding of the association between statin use and bleeding by a health-user effect.

Conclusion

Long-term statin use may be associated with a decreased risk for bleeding in warfarin users with atrial fibrillation. Additional research is needed to further explore this putative association.

Section snippets

Study Design and Data Sources

We used a large linked population-based administrative database in Ontario, Canada, to perform a nested case-control study from April 1, 1994, to March 31, 2002. Prescriptions were identified from the Ontario Drug Benefit Program, which records prescription medications dispensed to residents of Ontario who are age 65 years and older. Hospital admissions for upper gastrointestinal and intracranial bleeding were identified from the Canadian Institute for Health Information Discharge Abstract

Study Subject Characteristics

We identified 79,207 warfarin users with a history of atrial fibrillation, of whom 52% were women. The mean age at cohort entry was 79 years.

Statin Use and Risk for Any Bleeding (Upper Gastrointestinal or Intracranial)

During the period of observation, from April 1, 1994, to March 31, 2002, 1518 individuals from the warfarin cohort were admitted to a hospital with an upper gastrointestinal or intracranial bleed (cases) and were matched to 15,100 controls without a bleeding event (Table 1). Hospital admissions for upper gastrointestinal bleeding (n = 1201) were more common

Discussion

The principal finding of this study is that in warfarin users, long-term statin use seems to be associated with a decreased risk for bleeding complications. However, because new use of a statin does not seem to confer a protective effect against warfarin-associated bleeding, the possibility exists that a protective effect of long-term statin use against bleeding may be related to a “healthy user effect.” Thus, long-term statin users or their physicians may be more attentive to personal health

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  • Cited by (0)

    1

    Dr. Bell holds a Canadian Institutes of Health Research Phase 2 Clinician-Scientist Award.

    2

    Dr. Mamdani is currently an employee of Pfizer Inc, the manufacturer of one statin. The involvement of Dr. Mamdani in the development of this study and article was preceded by (∼6 months) and was not influenced by his subsequent decision to work for Pfizer.

    3

    Dr. Douketis, Dr. Bell, and Ms. Melo have no conflict of interest or financial disclosures.

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