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9/24/2004

Chest Physicians Release Warfarin Guidelines

Cheryl A. Thompson

Guidelines released this week on the use of warfarin and other vitamin K antagonists for anticoagulation differ little in content from the 2001 recommendations, with the authors continuing to report that clinicians have done a poor job of managing the therapy.

Despite the availability of anticoagulation management services, experienced personnel, and evidence-based guidelines on warfarin use, the authors wrote, many clinicians do not ensure that their patients achieve the level of anticoagulation recommended for their medical condition.

The guidelines—the result of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy, convened by the American College of Chest Physicians— were published as the supplement to the September issue of Chest, the organization's journal.

First held in the mid-1980s, the conference gathers experts in the prevention and destruction of blood clots that form along the wall of blood vessels. The goal is to sort through the cumulative evidence and produce guidelines for widespread use.

Henry I. Bussey, a conference attendee since 1985 and the lone pharmacist, said much of his efforts this time went toward rewriting the article on antithrombotic therapy in valvular heart disease to conform to the new format for the guidelines.

Bussey is also a coauthor of the article on vitamin K antagonists, the term now used by the conference to describe warfarin and agents with a similar mechanism of action. He is a professor at the College of Pharmacy at the University of Texas in Austin and cofounder of ClotCare Online Resource.

All of the conference's guidelines now display each recommendation immediately after the review of the literature supporting that decision. In addition, all of a guideline's recommendations appear at the end of the article's text, which had been the format in 2001.

The content of the conference's previous guidelines on oral anticoagulants—a pair of articles on mechanism of action, clinical effectiveness, optimal therapeutic range, and therapy management—appears in a single article on vitamin K antagonists, with the notable exception of the table listing the recommended therapeutic range for each medical condition.

In general, the recommendations on initiating and monitoring warfarin therapy did not change from 2001. These recommendations still have a conference-assigned status of Grade 2B or 2C, meaning that their benefit-to-risk ratio is not clear-cut for all patients and that the supportive evidence comes from randomized clinical trials with inconsistent results or methodological weaknesses or from observational studies.

An International Normalized Ratio (INR) of 2.0–3.0, which the various ACCP guidelines call a moderate- or standard-intensity INR, remains the target range for most patients needing therapy with a vitamin K antagonist. The exceptions, according to the guideline on vitamin K antagonists, are patients:

  • With an acute myocardial infarction (aim for an INR of 3.0–4.0 if not using aspirin or an INR of 2.0—3.0 with aspirin therapy; for details, see the guideline on antithrombotic therapy for coronary artery disease),
  • At high risk of a first myocardial infarction (aim for an INR of 1.5; for details, see the guideline on antithrombotic therapy for coronary artery disease), or
  • With a mechanical prosthetic heart valve and additional risk factors for atrial fibrillation; a caged ball or caged disk valve; or a mechanical prosthetic heart valve and who had a systemic embolism despite an INR in the target range (aim for an INR of 2.5–3.5 in conjunction with aspirin 75–100 mg/day; for details, see the guideline on antithrombotic therapy in valvular heart disease).

Regarding patients with a myocardial infarction, the guideline on antithrombotic therapy for coronary artery disease distinguishes between "most" health care settings and those "in which meticulous INR monitoring is standard and routinely accessible." Patients at most health care settings should receive aspirin therapy alone. But patients at the sites with better anticoagulation monitoring services should receive therapy with a vitamin K antagonist. Likewise, the guideline recommends therapy with a vitamin K antagonist in patients at high risk of a first coronary event who can receive INR monitoring "without difficulty."

Addition or withdrawal of "virtually any drug or herbal medicine" from the regimen of a patient treated with warfarin requires more-frequent measurement of the INR than usual, according to the guideline on vitamin K antagonists.

With a title that emphasizes warfarin's mechanism of action rather than route of administration, the guideline on vitamin K antagonists steers clear of an oral anticoagulant awaiting marketing approval by the Food and Drug Administration (FDA).

Ximelagatran, a direct thrombin inhibitor also known as Exanta, by AstraZeneca, can be taken orally and reportedly does not need INR monitoring to ensure safe anticoagulation.

An FDA advisory committee told the agency on Sept. 10 that it should receive more data on the safety of ximelagatran before approving the company's application to market the drug.