CMAJ • January 29, 2008; 178 (3). doi:10.1503/cmaj.1070132.
© 2008 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Letters

Combined antithrombotic therapy

Joseph A. Delaney, PhD, Lucie Opatrny, MD MSc, James M. Brophy, MD PhD and Samy Suissa, PhD

Division of Clinical Epidemiology, McGill University Health Centre, Montréal, Que.

[The authors respond:]

We read with interest David Good's comments on our paper on drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding.1 We agree that many patients have an indication for therapy with a combination of antithrombotic drugs because of severe illness. In our paper we gave the specific example of co-prescribing warfarin and acetylsalicylic acid, which was associated with a decrease in complications after myocardial infarction.2

The goal of our paper was to elucidate and document the degree of increased risk experienced by patients who are prescribed these combinations of antithrombotic medications in a primary care setting. Although some clinical trials may not show an increased risk of gastrointestinal bleeding among patients whose international normalized ratio is tightly controlled, it is unclear how well such results will carry over into the primary care setting, where the use of combination therapy can reasonably be expected to be broader than in a clinical trial setting. Clinical trials tend to have restricted eligibility (they may exclude patients at very high risk for gastrointestinal bleeding) and tighter surveillance of parameters like the international normalized ratio. The increased risk of bleeding we saw in our study (which was conducted using the United Kingdom General Practice Research Database) was also shown in a recent meta-analysis of randomized controlled trials.3

Although one possible interpretation of our findings is that warfarin, clopidogrel and acetylsalicylic acid should not be prescribed in combination because of the risk of gastrointestinal bleeding, this was not the intended message of our paper. Our goal was to increase physician awareness of the magnitude of these drug–drug interactions; this goal was acknowledged in the thoughtful commentary that accompanied our article.4 We hope to promote informed choice on the part of both patients and physicians as they consider the risks and benefits of combining these therapies.

Footnotes

Competing interests: None declared for Joseph Delaney, Lucie Opatrny and James Brophy. Samy Suissa has served as an advisory board member for Pfizer and Bristol-Myers Squibb, and he has received consultancy fees from Bristol-Myers Squibb. Samy Suissa has received consultancy fees from Sanofi-Aventis for Lantus and leflunomide but not for clopidogrel.


REFERENCES

  1. Delaney JA, Opatrny L, Brophy JM, et al. Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007;177:347-51.[Abstract/Free Full Text]
  2. Rothberg MB, Celestin C, Fiore LD, et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005;143:241-50.[Abstract/Free Full Text]
  3. Dentali F, Douketis JD, Lim W, et al. Combined aspirin–oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 2007;167:117-24.[Abstract/Free Full Text]
  4. Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ 2007;177:369-71.[Free Full Text]




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