New Formulations Might Be More Effective
By Annette M. Boyle
BETHESDA, MD – In the last 50 years, the use of anticoagulants has transformed mortality rates for deep vein thrombosis (DVT), pulmonary embolism (PE) and atrial fibrillation, and new anticoagulants and recommendations for use may save even more lives in the next few years.
“Improved diagnostics (CT scan) and effective treatments have greatly reduced mortality risk associated with venous thromboembolism,” according to a statement provided to U.S. Medicine by Lt. Col. Andrew P. Cap, MD, PhD, FACP, chief of blood research at the U.S. Army Institute of Surgical Research, associate professor of medicine at the Uniformed Services University and staff hematologist-oncologist at the San Antonio Military Medical Center, and Lt. Col. Todd Villines, MD, cardiology consultant to the Army Surgeon General and professor of medicine at the Uniformed Services University.
The first randomized controlled trial documenting any benefit of anticoagulation was published during the 1960s. In the following two decades, the risk of fatal pulmonary embolism from untreated DVT was about 16%. Today, treatment with anticoagulants has reduced the risk to less than 1%. The risk of death from unrecognized or untreated PE in the 1960s and 1970s has been estimated to be 30% to 65%, compared to current rates of about 2%.1
While anticoagulants were first used in DVT/PE, usage in other conditions has also achieved significant improvements in mortality rates. “The use of anticoagulation for the prevention of stroke and systemic embolism in patients with atrial fibrillation has been shown to dramatically reduce subsequent risk of cardioembolic events by more than 60%,” Villines and Cap said.
For those in the military, warfarin, the first and for years the only anticoagulant, was a double-edged sword. Using it saved lives; needing it ended careers.
“In a conscript Army, most soldiers with thrombotic disorders or other conditions requiring long-term anticoagulation would have been separated from service,” Cap and Villines said.
The situation is not as black and white today. While the need for long-term anticoagulation will still frequently trigger a medical board to determine fitness for continued service, as anticoagulated patients are generally considered nondeployable, other circumstances might allow a soldier to receive anticoagulants and stay in the service.
“Over the course of the last decade of conflict in Southwest Asia, many active-duty servicemembers have been treated for trauma-related DVT/PE. The duration of anticoagulation for most of these patients is three to six months and this duration of therapy does not trigger a medical board,” Villines and Cap noted.
Novel Oral Anticoagulants
While warfarin unquestionably improves patient outcomes for many conditions, it poses significant management challenges for patients and clinicians. It is contraindicated with many other medications, imposes dietary restrictions on patients, must be monitored at least monthly and requires frequent dosage adjustments to ensure anticoagulation stays in the therapeutic range. Several novel oral anticoagulants (NOACs) which have received Food and Drug Administration approval since 2010 do not have these issues.
These drugs — dabigatran, rivaroxaban and apixaban — have been shown to work just as well or better than warfarin in most instances and are much easier to manage. As a result, their use has soared. Nationwide, 62% of new anticoagulant prescriptions were written for one of these new medications by mid-2013, according to a recent study in the American Journal of Medicine. Because they cost significantly more than warfarin, they accounted for 98% of anticoagulant related costs.2
As of early 2014, the novel anticoagulants accounted for about 20% of anticoagulant prescriptions within the DoD healthcare system, according to the DoD’s Pharmacoeconomic Center and only 7% of prescriptions for anticoagulants within the VA.
Within the DoD and VA settings, clinicians have somewhat less reason to switch quickly from warfarin to the newer agents, as both healthcare systems have developed pharmacist-managed anticoagulation clinics which minimize the monitoring issues that pose significant concerns for patients in the general population. Many clinicians and patients remain cautious of some of the newer anticoagulants because they lack reversal agents that can be used in life-threatening bleeding events, though a number of reversal agents are in development.
Still, the use of novel anticoagulants has significantly increased across the military healthcare system since their introduction and is expected to continue to rise as physicians and patients become more comfortable with them, particularly as research on their effectiveness continues to build.
“Literature to date suggests that, in patients with atrial fibrillation, novel anticoagulants may be superior to warfarin for reducing the rates of death and stroke (particularly hemorrhagic stroke) and they are safe when prescribed in accordance to guidelines,” Cap and Villiines said.
Revisions to guidelines on the management of atrial fibrillation released this year reflect the improved outcomes attributed to anticoagulants. The new guidelines expanded the number of patients eligible for treatment with anticoagulation therapy and strongly favor anticoagulants, including NOACs, over anti-platelet drugs such as aspirin, they noted.
1 Kelly J, Hunt BJ. Do anticoagulants improve survival in patients presenting with venous thromboembolism? J Internal Medicine. 2003;254:527-539.
2 Desai NR, Krumme AA, Schneeweiss S, Shrank WH, Brill G, Pezalla EJ, Spettell CM, Brennan TA, Matlin OS, Avorn J, Choudhry NK. Patterns of Initiation of Oral Anticoagulants in Patients with Atrial Fibrillation — Quality and Cost Implications. Am J Med. 2014 May 20. pii: S0002-9343(14)00399-4