The Dire Need for Effective Anticoagulant Therapy

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The MD Magazine Peer Exchange “Novel Anticoagulation Options: Target-Specific Oral Agents and Their Antidotes” features leading physician specialists discussing key topics in anticoagulation therapy, including the clinical characteristics of current and emerging agents and criteria for use in specific patient populations.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

• Scott Kaatz, DO, MSc, Chief Quality Officer at Hurley Medical Center in Flint, Michigan, and clinical associate professor at Michigan State University
• Seth Bilazarian, MD, clinical and interventional cardiologist at Pentucket Medical and instructor of medicine at Harvard Medical School
• Gerald Naccarelli, MD, Bernard Trabin Chair in Cardiology, professor of medicine and chief of the Division of Cardiology at Penn State University School of Medicine, and associate clinical director at Penn State Heart and Vascular Institute in Hershey, Pennsylvania
• Christian T. Ruff, MD, associate physician in the cardiovascular medicine division at Brigham and Women’s Hospital, and assistant professor of medicine at Harvard Medical School in Boston

In this segment of the Peer Exchange, the panelists discuss why there is such an urgent need for anticoagulant therapy for patients with atrial fibrillation, the benefits of effective therapy, and the challenges associated with warfarin treatment.

Dr. Naccarelli opens the discussion by noting there are 3-6 million people in the US with atrial fibrillation, many of whom are asymptomatic. Epidemiologic studies have shown that in the next 30 years or so, this number may double or even triple because atrial fibrillation is a “disease of aging.”

Patients with atrial fibrillation, especially those with comorbidities, have a five-fold increase in their risk of stroke, which translates into about 75,000 strokes every year in the US related to atrial fibrillation.

The bad news is that strokes in patients with atrial fibrillation tend to be much more severe than strokes in patients without atrial fibrillation. These bigger strokes are more likely to be disabling, are more likely to recur, and are more likely to kill the patient, said Dr. Naccarelli.

Unfortunately, multiple studies and real-life clinical experience have shown that many patients are not being treated with an effective anticoagulant (as discussed in the first segment of this Peer Exchange, aspirin does not count), despite the fact that treatment with an anticoagulant such as warfarin reduces the risk of stroke by two-thirds.

“We’ve known warfarin can reduce the risk of stroke by two-thirds since 1988; that’s over 25 years ago. And yet half of the patients in the United States are not on a real anticoagulant that should be. I think we can do better than this,” said Dr. Naccarelli.

He said the problem with warfarin is not that it doesn’t work; the problem is that “it only works two out of three times. It doesn’t work three out of three times. Now we’re going to compare that standard against the new therapies, all of which are at least as good as that and, in some cases, better than that.”

However, warfarin treatment comes with several challenges. One of which, said Dr. Bilazarian, is that warfarin is a very difficult drug to titrate. Another issue is that often patients receive care from several physicians, some of whom may not be attentive to drug interactions associated with warfarin. “For example, patients will go to an urgent care center to get treatment for a respiratory infection or a urinary tract infection. They get started on an antibiotic, and then their anticoagulation goes awry,” said Dr. Bilazarian.

Another challenge is adherence to therapy. Bilazarian said about 10 percent of patients in his warfarin management center have “very solid times in therapeutic range, but the vast majority of patients, when we review their previous six months of treatment, have at least one or two periods that are outside therapeutic range‑‑not dramatically out but often. So it’s really very challenging.”

Patients on warfarin therapy must also maintain an effective diet for cardiovascular risk prevention, including limiting their intake of alcohol and leafy green vegetables.

Warfarin is also associated with a high rate of drug related emergency department visits among elderly patients. Dr. Kaatz noted that warfarin and other anticoagulants are the number one cause of adverse drug reactions to lead to hospitalization.

He said that last year the federal government “put together an inter-federal agency and came out with a national action plan on adverse drug reactions, and reported that the three drugs that caused more than half of all hospital admissions for adverse drug reactions are opioids, diabetic agents, and anticoagulants. Anticoagulants lead the pack in hospitalization, and pragmatically that’s warfarin-related.”