Rivaroxaban associated with more GI bleeding than warfarin; fatal GI bleeds rare

Compared with warfarin, rivaroxaban was associated with increased gastrointestinal bleeding, according to new data from the ROCKET AF trial.

However, rates of severe gastrointestinal (GI) bleeding were similar between both drugs, and fatal GI bleeding was rare, researchers found.

Matthew W. Sherwood, MD, MHS, and colleagues analyzed 14,236 patients from the on-treatment arm of ROCKET AF, the pivotal trial that led to FDA approval of rivaroxaban (Xarelto, Janssen Pharmaceuticals), a novel oral anticoagulant.

The primary outcome was adjudicated GI bleeding from the first dose of the study drug until 2 days after the last dose.

Sherwood, from the division of cardiovascular medicine at Duke University Medical Center and Duke Clinical Research Institute, and colleagues found that the 684 patients who experienced GI bleeding were older (median age, 75 years vs. 73 years) and more likely to be men than those who did not. Forty-eight percent of bleeds occurred in the upper GI tract vs. 23% in the lower GI tract and 29% in the rectum, with no differences between the therapies.

GI bleeding rates higher

The rates of major or nonmajor clinically relevant GI bleeding were 3.61 events per 100 patient-years for those assigned rivaroxaban and 2.6 events per 100 patient-years for those assigned warfarin (HR = 1.42; 95% CI, 1.22-1.66).

The researchers found no significant differences in rates of severe GI bleeding requiring transfusion of at least four units (rivaroxaban, 0.47 events per 100 patient-years; warfarin, 0.41 events per 100 patient-years; HR = 1.19; 95% CI, 0.8-1.77) or of fatal GI bleeds (rivaroxaban, 0.01 events per 100 patient-years; warfarin, 0.04 events per 100 patient-years; HR = 0.21; 95% CI, 0.02-1.76). There were only six fatal GI bleeding events during the study period, five of which occurred in the warfarin arm.

They identified the following independent predictors of GI bleeding: anemia at baseline (HR = 1.7; 95% CI, 1.41-2.04), previous GI bleeding (HR = 2.11; 95% CI, 1.62-2.76), long-term aspirin use at screening (HR = 1.47; 95% CI, 1.26-1.72), advanced age (HR = 1.11; 95% CI, 1.06-1.17 per 5-year increase), lower diastolic BP (HR = 1.1; 95% CI, 1.05-1.16 per 5-mm Hg decrease to < 80 mm Hg), current or former smoking (HR = 1.37; 95% CI, 1.16-1.62), current or former sleep apnea (HR = 1.6; 95% CI, 1.22-2.1), proton-pump inhibitor use at baseline (HR = 1.36; 95% CI, 1.12-1.65), lower creatinine clearance (HR = 1.06; 95% CI, 1.01-1.12 per 5-unit decrease to < 60 mL/min), chronic obstructive pulmonary disease (HR = 1.3; 95% CI, 1.05-1.61), male sex (HR = 1.21; 95% CI, 1.01-1.44) and baseline non-aspirin antiplatelet use (HR = 1.5; 95% CI, 1.02-2.21).

Modifiable risk factors key

In a related editorial, Gregory Y.H. Lip, MD, and Deidre A. Lane, PhD, wrote that the study authors “emphasize the need for minimizing modifiable risk factors for GI bleeding in patients on [oral anticoagulation], which is a very sensible approach.” Both are from the Aalborg Thrombosis Research Unit, department of clinical medicine, Aalborg University, Denmark; Lip is also from the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, England.

They also wrote that the GI bleeding risk associated with rivaroxaban in the ROCKET AF study was higher in patients from North America (HR = 1.89; 95% CI, 1.45-2.45) than in those from the rest of the world (HR = 1.21; 95% CI, 1-1.47), perhaps because in the warfarin arm, those in North America had more time in therapeutic range compared with those in the rest of the world, “and bleeding on warfarin is very closely related to [time in therapeutic range]. … Poor anticoagulation control (ie, labile INRs) translates into an excess of thromboembolism, mortality and bleeding.” – by Erik Swain

Disclosures: The study was funded by Janssen Research & Development LLC and Bayer HealthCare AG. Sherwood reports receiving consulting fees from Boehringer Ingelheim and educational grants from AstraZeneca and Gilead. See the full study for a list of the other researchers’ relevant financial disclosures. Lip reports financial ties with Bayer, Biotronik, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Medtronic, Merck, Roche and Sanofi. Lane reports financial ties with Bayer, Boehringer Ingelheim and Bristol-Myers Squibb/Pfizer.

Source: www.healio.com