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Biomarker predictive of adverse events in anticoagulated patients with atrial fibrillation

Roldán V. J Am Coll Cardiol. 2011;doi:10.1016/j.jacc.2010.12.033.

Serebrauny V. J Am Coll Cardiol. 2011;doi:10.1016/j.jacc.2011.02.025.

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Plasma von Willebrand factor levels among patients with atrial fibrillation who were anticoagulated were found to be an independent risk factor for adverse events, including cardiovascular mortality and major bleeding, study findings suggested.

“Atrial fibrillation patients constitute a high-risk population with both cardiovascular and hemorrhagic events,” Vanessa Roldán, MD, PhD, and study researchers said. “In this study, we showed for the first time how an increased plasma [von Willebrand factor] level, an established marker for endothelial damage/dysfunction, is associated with an adverse prognosis in atrial fibrillation patients, with regard to cardiovascular (mainly thrombotic) events, mortality and bleeding.”

The study featured 829 patients (median age, 76 years) who had permanent atrial fibrillation and were stabilized for at least 6 months on anticoagulation therapy with an international normalized ratio (INR) of between 2 and 3. In addition, all patients were followed for a median of 828 days for adverse events, including mortality, major bleeding, and thrombotic and vascular events.

During follow-up, investigators found the following risk factors for a composite of cardiovascular events, including stroke, acute coronary syndrome and acute heart failure: high levels of plasma von Willebrand factors (vWF; ≥221 IU/dL; P<.001), age 75 years and older (P=.005), heart failure (P=.006) and previous stroke (P=.012). Similarly, for cardiovascular death, vWF levels (P=.011), age of at least 75 years (P=.01) and HF (P=.023) were all significant risk factors, as were smoking (P=.008) and hypercholesterolemia (P=.038).

According to researchers, vWF levels proved to be independently associated with major bleeding (P<.001) and were able to refine clinical risk stratification schema for stroke and bleeding.

In an accompanying editorial, Victor L. Serebruany, MD, PhD, of Johns Hopkins University, said important implications can be drawn from the results.

“First, serial assessment of vWF in atrial fibrillation patients is urgently needed to better validate this promising biomarker, linking its immediate changes to the timing of adverse events,” Serebruany said. “Second, it is unclear to what degree the choice of an antithrombotic will affect the ability of soluble vWF to predict prognosis. This is especially true because warfarin [Coumadin, Bristol-Myers Squibb] is currently being aggressively substituted with novel thrombin inhibitors.”

He said the data must be confirmed in a properly designed and adequately powered randomized trial.

Disclosure: Dr. Serebruany reported no relevant financial disclosures.

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