Factors Associated With Major Bleeding Events: Insights From the Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

Study Questions:

What factors are associated with major bleeding in atrial fibrillation patients in the ROCKET AF study?

Methods:

In ROCKET AF, patients were randomized to receive fixed-dose rivaroxaban 20 mg daily (or 15 mg daily in patients with a creatinine clearance of 30-49 ml/min) or adjusted-dose warfarin (target international normalized ratio range of 2.0-3.0). The principal safety endpoint was defined as major bleeding or nonmajor clinically relevant bleeding. The authors examined the effect of rivaroxaban and warfarin on the risk of major bleeding. A multivariable model was used to compare demographic and clinical characteristics of patients with and without major bleeding.

Results:

Rates of major bleeding or nonmajor clinically relevant bleeding were similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 event per 100 patient-years; hazard ratio [HR], 1.03 [0.96, 1.11]). The following characteristics were independently associated with major bleeding risk: increasing age, baseline diastolic blood pressure ≥90 mm Hg, history of chronic obstructive pulmonary disease, history of gastrointestinal (GI) bleeding, prior aspirin use, and anemia. Female gender and diastolic blood pressure <90 mm Hg were associated with decreased risk. The only predictor for bleeding that interacted with study treatment was prior history of GI bleeding; those taking rivaroxaban, compared to those taking warfarin, were at higher risk of major bleeding if they had a prior history of GI bleeding (HR, 2.33 [1.39, 3.88]).

Conclusions:

There are several baseline characteristics that are associated with major bleeding risk in the ROCKET AF cohort. With the notable exception of GI bleeding, which was significantly associated with major bleeding in patients randomized to rivaroxaban but not warfarin, the other risk factors (age, female gender, diastolic blood pressure, history of chronic obstructive pulmonary disease, aspirin use, and anemia) were associated with the same risk of bleeding in both patients receiving warfarin or rivaroxaban.

Perspective:

The authors presented a useful analysis that corroborates the safety of rivaroxaban compared to warfarin. The finding of GI bleeding being significantly associated with major bleeding in patients randomized to rivaroxaban (but not warfarin) is clinically relevant, and should inform decision making about options for stroke prophylaxis in patients with atrial fibrillation.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Vitamin K, Morpholines, Thiophenes, Warfarin, Blood Pressure, Risk Factors, Gastrointestinal Hemorrhage, Pulmonary Disease, Chronic Obstructive, Factor Xa, Hemorrhage


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