The emergence of a new generation of anticoagulants, including the direct thrombin inhibitor, dabigatran and the factor Xa inhibitor, rivaroxaban, has the potential to significantly change the business of thinning blood in the United States. For years warfarin has been the main therapeutic option for patients with health conditions such as atrial fibrillation, venous thrombosis, artificial heart valves and pulmonary embolus, which are associated with excess clotting risk that may cause adverse outcomes, including stroke and death. However, warfarin therapy is fraught with risk and liability. The drug interacts with food and many drugs and requires careful monitoring of the prothrombin time (PT) and international normalized ratio (INR).
Recently, when I applied for credentialing as solo practioner, I was asked by my medical malpractice insurer to detail my protocol for monitoring patients on anticoagulation therapy with warfarin. When I worked in group practice at the Emory Clinic in Atlanta I referred my patients to Emory’s Anticoagulation Management Service (AMS), which I found to be a wonderful resource. In fact, “disease management” clinics for anticoagulation are common amongst group practices because of the significant liability issues. Protocol based therapy and dedicated management teams improve outcomes for patients on anticoagulation with warfarin. I spoke with Dr. Donald Davis, Medical Director of the Emory Anticoagulation Management Service, who noted that the AMS was originally established as a service to promote patient safety. However, it has also proved to be lucrative for Emory Healthcare. Currently Emory’s AMS has expanded to seven locations in metro Atlanta and cares for 3,400 patients. Piedmont Hospital, the Atlanta VA Medical Center and Kaiser have similar programs. Patients on blood thinners come in as often as two to three times monthly for a nurse visit and monitoring of their PT and INR. A patient of mine on chronic warfarin therapy recently shared his medical bills with me, questioning the high fees he was charged for each of his anticoagulation clinic visits. Fortunately for him, his health insurance will foot those bills.
The advantage of the newer drugs, dabigatran and rivaroxaban, is that they do not require laboratory monitoring and do not appear to interact with other drugs and foods. Dabigatran was recently approved by the FDA based on results of RE-LY, which compared it to warfarin in patients with atrial fibrillation for prevention of stroke. At a dose of 110 mg twice daily dabigatran had similar efficacy and lower bleeding risk than warfarin. At a higher dose (150mg twice daily) it had superior efficacy and equivalent risk of hemorrhage. For now, dabigatran’s approval is limited to the prevention of stroke in patients with non-valvular atrial fibrillation. However, the RE-COVER trial compared dabigatran to warfarin in patients with venous thromboembolism. In this trial the drugs were found to have equivalent efficacy, though dabigatran was found to have a lesser risk of major bleeding. Dabigatran is currently approved for use in Europe for the prevention of venous thromboembolism in patients undergoing orthopedic surgery. It has not yet been approved for this indication in the United States.
Another blood thinner, the factor Xa inhibitor, rivaroxaban’s efficacy has been demonstrated in the recently published results of the Acute DVT and Continued Treatment Study of the EINSTEIN program. In these trials rivaroxaban therapy was compared with standard therapy for acute DVT with enoxaparin followed by a vitamin K agonist (i.e. warfarin). Rivaroxaban at an initial dose of 15 mg twice daily and then 20 mg once daily was found to have similar efficacy and risk. In the Continued Treatment Trial rivaroxaban was compared with placebo and found to reduce the incidence of recurrent thrombotic events and to have an acceptable risk of bleeding. FDA approval of rivaroxaban is still pending.
There has been significant discussion about the cost of these newly developed drugs. At Publix pharmacy in Atlanta dabigatran runs $271.95 for sixty 150 mg tablets. A recent study published in the Annals of Internal Medicine found the drugs are likely to be cost-effective. After reviewing my patient’s bills from anticoagulation clinic I can attest to the likelihood that the drugs will be cost-effective when taking into account the lab and office visit fees required for monitoring. However their use will create a shifting of reimbursement away from medical centers (anticoagulation clinics) to the pharmaceutical industry. If insurers don’t cover the full cost of these drugs consumers could bear more costs. Health systems, such as the Veterans Administration or Emory Healthcare, that have established anticoagulation programs, may have to reorganize as the need for intense monitoring becomes obsolete. Will the need for reorganization slow the adoption of new anticoagulants onto hospital formularies? As with any new drug, the long term safety of dabigatran and rivaroxaban has not been proven. In 2006 a direct thrombin inhibitor, ximelagatran, was pulled from the market because it was found to cause liver toxicity. What occurs with anticoagulation adoption and use within the United States could prove to be an interesting example of how economic conflicts of interest drive medical decision-making.
Time will tell how the new anticoagulants compare with warfarin in terms of safety and efficacy. However, it seems likely that economics will be a factor in the way in which these drugs are adopted and used in medical practice. But, let's hope that the primary factor will be the health and quality of life of our patients.