Circ: Threshold for warfarin for AF stroke risk higher now

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While ischemic stroke linked to atrial fibrillation (AF) has declined over the past two decades, whether or not to anticoagulate these patients remains debatable, and a model suggests the threshold to do so is higher, according to a study published online Dec. 7 in Circulation: Cardiovascular Quality and Outcomes.

“Patients at lower risk of stroke and at high risk of bleeding should not receive oral anticoagulant therapy; patients at higher risk of stroke and at low risk of bleeding should receive anticoagulant therapy,” the authors wrote. “The more difficult decisions lie in the middle where the risks of stroke and bleeding are more closely balanced. Here lies the so called ‘tipping point.’”

To better understand these types of decisions as well as the trends in the risks and benefits of anticoagulation therapy in nonvalvular AF patients, Mark H. Eckman, MD, of the University of Cincinnati Medical Center in Ohio, and colleagues used a decision analytic model to assess strategies of oral anticoagulant therapies with warfarin, no antithrombotic therapy and aspirin across various values for risk of ischemic stroke.

In addition, the researchers evaluated upcoming anticoagulants such as dabigatran (Pradaxa, Boehringer Ingelheim) or Xa inhibitors that would impact the “tipping point” for these types of therapy.

The decision model evaluated outcomes of four treatment strategies: anticoagulation with warfarin, anticoagulation with dabigatran, aspirin therapy or no antithrombotic therapy. For the base case, the researchers used a hypothetical 69-year-old man with nonvalvular AF, with a CHADS2 score of 2 and no contraindications to warfarin therapy.

The researchers found that warfarin therapy increased quality-adjusted life expectancy when compared with no antithrombotic therapy or aspirin, 9.36 versus 9.11 and 9.25 quality-adjusted life-years, respectively.

In addition, the researchers found that patients with a CHADS2 score of zero or 1 should receive aspirin, while those with a score of 2 or greater should receive warfarin therapy.

“The overall impact of the declining risk of ischemic stroke for any CHADS2 score was to shift the tipping point so that a higher CHADS2 score is needed to ‘justify’ anticoagulant therapy,” the authors wrote.

The researchers also noted that when treated with the new, “safer” agent dabigatran, the threshold for ischemic stroke risk above which anticoagulant therapy is preferred over aspirin is lower, 0.9 percent per year.

The Tipping Point
“Our analysis suggests that the tipping point, the threshold of ischemic stroke risk below which anticoagulant therapy should be withheld and above which anticoagulant therapy should be prescribed, has changed,” Eckman and colleagues wrote.

“The risk of ischemic stroke in nonvalvular AF appears to have declined, perhaps as a result of more aggressive control of blood pressure and lipid levels.”

The results showed that the threshold has shifted the balance of risk and benefit and is now in favor of warfarin at a higher CHADS2 score then previously. Not prescribing any antithrombotic therapy is only recommended for patients at almost no risk of ischemic stroke.

“[P]atient-specific differences in bleeding risk or preferences for health outcomes, along with statistical uncertainty in parameter estimates, may affect the strength of this result,” the authors noted. “Furthermore, the magnitude of gain from warfarin increases as the annual rate of ischemic stroke increases above the threshold.”

The researchers offered that older guidelines may have been a bit too “conservative” about warfarin and said that the current American College of Chest Physicians and American College of Cardiology, American Heart Association and European Heart Society guidelines are appropriate due to the decreased risk of ischemic stroke.

"In summary, secular trends in the risk of ischemic stroke as with the proliferation of new anticoagulants and antithrombotic therapies, along with nonpharmacological interventions for AF, and the improbability of clinical trials performing head-to-head comparisons of these treatments, a decision analytic framework can be used to examine new treatments as data become available,” the authors concluded.

“Finally, it is clear that the biggest barrier to personalized decision-making for patients with AF remains the limited discriminating ability of available tools for predicting risk of thromboembolic stroke and hemorrhage.”