Rivaroxaban bleeding rates similar in real world to trial results

Last Updated: 2015-01-23

By Will Boggs MD

NEW YORK (Reuters Health) - Major bleeding rates associated with rivaroxaban use in patients with nonvalvular atrial fibrillation (NVAF) in real-world experience are similar to rates seen in clinical trials supporting its registration, according to a pharmacovigilance study of 27,467 patients.

"In the setting of NVAF and a CHADSVASC (congestive heart failure+vascular) score of 2 or higher, the risk of anticoagulation is smaller than the risk of 'no anticoagulation,'" Dr. W. Frank Peacock, of Baylor College of Medicine, Houston, Texas, told Reuters Health by email. "Dying from major bleeding while on rivaroxaban is very rare."

Major bleeding associated with rivaroxaban treatment occurred in 3.6 per 100 person-years in patients in the ROCKET-AF trial, but questions remain regarding the bleeding risk in rivaroxaban patients treated in real-world clinical settings.

Dr. Peacock and colleagues used data from a five-year, observational, post-marketing safety surveillance study to estimate major bleeding rates with rivaroxaban use in patients with NVAF and the factors associated with such bleeding.

The incidence of major bleeding came to 2.86 per 100 person-years overall, including 2.68 per 100 person-years in men and 2.99 per 100 person-years in women, according to the January 14 Clinical Cardiology online report.

The fatal bleeding rate was very low at 0.08 per 100 person-years.

Factors associated with major bleeding included older age, comorbidities, and higher congestive heart failure scores.

Major bleeding occurred most commonly in the gastrointestinal tract (88.5%) and intracranially (7.5%).

Just under half of the 464 hospitalized patients (46.7%) required a blood transfusion, but 43.3% of them required intensive care unit transfer and a quarter required a surgical intervention during their major bleeding hospitalization.

"Though the results are not intended for any direct comparison, these findings are generally consistent with those reported in the previous large randomized FDA registration trial of rivaroxaban," the investigators say.

"The majority of patients with a CHADSVASC (congestive heart failure+vascular) score of 2 or higher should receive anticoagulation, preferably with a TSOAC (target-specific oral anticoagulant), and the very small (but real) concern for fatal bleeding should be weighed against the higher probability of having a stroke and its awful consequences," Dr. Peacock concluded.

"Overall, the TSOACs have a faster onset and are safer than Coumadin. Coumadin should go away, except for artificial heart valves and a minority of rare cases where there is no substitute. The lawyers who are on TV suggesting the TSOACs are less safe than Coumadin are doing a disservice to the American public, and they should try a course of Coumadin themselves," he added.

Dr. Eugene Yang, of the University of Washington Medical Center, Bellevue, recently reviewed the use of TSOACs for stroke prevention in NVAF patients. He told Reuters Health by email, "When choosing an appropriate anticoagulant for stroke prevention in NVAF patients, a thorough history and review of prescription and nonprescription medications are critical. Based on this report and previously published data, rivaroxaban may not be a proper choice for older patients and those with chronic kidney disease." [His paper is here: http://1.usa.gov/1CmdGZA ]

"Since this is an observational, retrospective analysis, results from this report should be interpreted with caution and are hypothesis-generating only," Dr. Yang said.

Dr. Partha Sardar, of New York Medical College, New York, agreed in an email to Reuters Health: "Major bleeding with rivaroxaban is mostly gastrointestinal and fatal bleeding is rare, but this conclusion needs validation from future real world care-control study. These results were from retrospective analyses and should be interpreted cautiously, and no strong recommendation is possible from this data which might influence current practice."

Results of a network analysis published in November 2014 indicated that major bleeding rates were significantly higher with rivaroxaban than with apixaban, dabigatran, or edoxaban. (http://1.usa.gov/1BkT7LM)

Janssen Scientific Affairs, LLC and Bayer Healthcare funded the studied, employed 5 of the 10 authors, and had various relationships with 4 other authors.

SOURCE: http://bit.ly/1y8FEln

Clin Cardiol 2015.