When measuring novel anticoagulants, proceed with caution

The beauty of novel oral anticoagulants is that they come in fixed doses and don’t require monitoring, as warfarin does. Still, some circumstances warrant an assay, and clinicians should be aware of the potential pitfalls.

In recent years, the FDA has approved new alternatives to warfarin to reduce the risk of stroke in patients with nonvalvular atrial fibrillation: dabigatran (Pradaxa, Boehringer Ingelheim), a direct thrombin inhibitor; rivaroxaban (Xarelto, Janssen Pharmaceuticals/Bayer HealthCare), a Factor Xa inhibitor; and apixaban (Eliquis, Bristol-Myers Squibb and Pfizer), another Factor Xa inhibitor. While these novel drugs remove the burden of monitoring, there are times when their anticoagulant activity needs measurement, such as cases of bleeding or suspected noncompliance.

In a study published in the Sept. 16 issue of the Journal of the American College of Cardiology, Adam Cuker, MD, MS, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues evaluated and summarized existing evidence on laboratory measurement of these three newcomers. Their goal was to help cardiologists understand anticoagulation tests when they are warranted.

For their analysis, Cuker et al searched PubMed and the Web of Science through Dec. 1, 2013, for monitoring tests for dabigatran, rivaroxaban and apixaban and reviewed the results. They determined that monitoring is helpful when there is a suspicion of excess effect such as an overdose or bioaccumulation, suspicion of therapeutic failure, for bleeding or for evaluating a planned invasive procedure.    

But there is no one-size-fits-all solution. “An ideal assay would thus show adequate linearity, sensitivity, and reproducibility to enable quantification across a broad range of drug levels,” they wrote. With one exception, no one assays meets that standard. They encouraged cardiologists to be cognizant of how these assays may perform in various ranges.

“Each drug produces unique effects on coagulation assays,” Cuker et al wrote. “Our systematic review provides guidance to the clinician on how to use and interpret coagulation results.”

But they cautioned more research is needed to clarify the relationship between drug levels, test results and outcomes.