Warfarin: Still the gold standard

Despite the new oral anticoagulants, warfarin remains the drug of choice, keeping the door open for point-of-care PT testing

It has been four years since a new class of blood thinners – which eliminate the need for regular monitoring – hit the market. Even so, in 2014, the old stalwart, warfarin (Coumadin®), remains the king of the class. That’s good news for Repertoire readers, many of whom sell point-of-care prothrombin-time (PT) tests for people on warfarin. But it’s also good news for millions of patients and doctors, who continue to find warfarin reliable and inexpensive.

The new drugs – PRADAXA®, XARELTO® and ELIQUIS® – have made a dent in the market. Annual PRADAXA sales are reported to be in the $1 billion range. But they are significantly more expensive than warfarin. And questions have arisen as to whether the drugs lead to internal bleeding. A class action lawsuit against Boehringer Ingelheim, maker of PRADAXA®, has brought the issue to the fore.

“Doctors aren’t running out and moving all of their warfarin patients over to the new anticoagulants,” says Tim Huston, director of marketing, Roche Diagnostics. Warfarin prescriptions are still an estimated 33 million annually. Roche markets the CoaguChek® XS system, which gives physicians a PT/INR result – which provides a status of their patients’ blood-clotting time – in about one minute.

“There hasn’t been any reason to move them to the newer oral anticoagulants if they are stable and well controlled on warfarin,” says Huston. To make the point, he quotes a study by David A. Garcia, M.D., of the University of Washington, in The Journal of Thrombosis and Thrombolysis, in which Garcia says, “Patients on a highly stable, therapeutic dose of warfarin should not expect better outcomes by switching.”

New class of anticoagulants
Coumadin was introduced by Bristol-Myers Squibb in 1954, and is used to help prevent and treat blood clots in the legs and lungs, as well as clots associated with heart-valve replacement or atrial fibrillation. It does so by blocking vitamin K, a clotting factor. Patients on warfarin need regular PT/INR tests, which help the physician ensure that the drug is helping the patient maintain a balance between clot prevention and excessive bleeding. The drug costs pennies a day.

In October 2010, Boehringer Ingelheim introduced PRADAXA, which binds with thrombin to prevent blood clots from forming. Janssen Pharmaceuticals followed in July 2011 with FDA approval to market XARELTO (manufactured by Bayer HealthCare). In December 2012, Bristol-Meyers Squibb and Pfizer received FDA approval to market ELIQUIS. (In January 2014, Daiichi Sankyo submitted a fourth drug, SAVAYSA™, to the FDA for marketing clearance.) XARELTO, ELIQUIS and SAVAYSA are similar in that they inhibit the production of thrombin by targeting an enzyme, Factor Xa.

Bigger market for anticoagulants
“Certainly, since the new anticoagulants have been introduced, certain patient populations have benefited from them, which is great,” says Huston. In fact, the total number of patients taking oral anticoagulants, including warfarin, has risen, at a rate of about 2 percent per year, he adds.

“The real trend we see is this,” he continues. “As patients come in to the healthcare system, if they’re only going to be on blood thinners for a short period of time, the new anticoagulants might be the right therapy, especially for procedures such as knees or hips, where the patient could be relatively healthy. But for patients who need long-term therapy – and there are certain indications that the new oral anticoagulants aren’t recommended for, such as mechanical heart valves – warfarin will continue to be the drug of choice.”

Already, the market is seeing some jockeying among the manufacturers of the new anticoagulants, who are targeting similar patient populations. “PRADAXA was the first to come out, but when measuring the number of new and renewal prescriptions, XARELTO has overtaken it,” says Huston. Meanwhile, the makers of ELIQUIS are hitting the airwaves with ads.

Limitations of new drugs
But the new drugs are not without limitations. They lack an antidote. In other words, if the patient suffers from excessive bleeding, there’s no effective way to stop it. (In contrast, patients on warfarin can receive injections of vitamin K to slow down the bleeding process.)

What’s more, without regular monitoring, the clinician and patient can’t be sure the patient’s PT/INR is responding to the drug. Moreover, the physician has no way to know if the patient in his or her office has been compliant with the recommended dosage. All these concerns are causing some clinicians to suggest that perhaps patients on the new drugs should be monitored regularly, as are those on warfarin. (That said, no effective point-of-care tests are available to monitor prothrombin time among patients on the new anticoagulants. “It’s something we’re looking into,” says Huston.)

With the daily cost of these new drugs reported to be in the $7-$8 range, the total cost to patients and providers is an issue. “Much of what we hear in the marketplace revolves around that,” says Huston.

Opportunities for sales reps
“One of the key things we tell our sales team is that there’s good news to come with the introduction of new oral anticoagulants,” says Huston. “[Drug makers] are educating the patient population on the benefits of going on an oral anticoagulant. There are a large number of people who should be on an anticoagulant but who have not been diagnosed; and there are many who have been diagnosed, but are not using an anticoagulant. So the marketing of these drugs is bringing some focus to the area, and expanding the number of patients being considered for warfarin therapy.

“It comes down to the physician trying to figure out what is the right drug therapy for his or her patients. And warfarin is still the gold standard, because physicians have the ability to know where their patients are [in terms of blood clotting].”

Repertoire readers should continue to probe their physician customers’ knowledge and usage of point-of-care testing. As many as 45 to 50 percent of warfarin patients are still being sent to a lab for a venous draw, vs. getting a quick, fingerstick, point-of-care test at their physician’s office, says Huston. “There’s a huge opportunity to shift patients to point-of-care therapy. That’s where the patient, provider and distributor all win. The doctor gets immediate results, with the patient sitting in the office; and the distributor picks up testing revenue that he or she might not otherwise have had.”

“When we talk to our distribution partners, we’re talking about the opportunity that exists out there. That’s the exciting part. We’re in control of that. And that’s the message our distribution reps are bringing to the market.”

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Warfarin and PT testing

For some, an ordinary cut to the skin can present dangerous health issues. Typically, when the body sustains a wound, the blood clots. Under normal circumstances, this is a healthy response, as clotting helps the body heal itself. But under certain circumstances – e.g., among patients with atrial fibrillation, deep vein thrombosis, pulmonary embolism or mechanical heart valves – this same mechanism can cause a life-threatening clot or “thrombus” to form. That’s why patients with these conditions must take oral anticoagulants, which decrease the clotting ability of the blood.

The most widely used anticoagulant, warfarin (Coumadin®), inhibits the formation of blood clots. It is considered to have a narrow therapeutic range, and the response to a standard dose varies widely both among patients and within patients over time. Changes in patient health, lifestyle or diet can affect changes in the action of the anticoagulant. That’s why patients taking warfarin must be tested frequently to make sure they are taking the proper level of the drug.

Prothrombin time (PT) is a blood test designed to measure how long it takes a patient’s blood to clot. It helps physicians monitor how well warfarin is maintaining a balance between clot prevention and excessive bleeding.

Because normal PT values can vary from one test site to the next, a method of standardizing prothrombin test results, called the international normalized ratio (INR) system, was developed. The INR system enables doctors to understand and interpret the PT test universally, ensuring that anticoagulant therapy is the same no matter who prescribes it.