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Pharmacoepidemiol Drug Saf. 2018 Mar;27(3):263-271. doi: 10.1002/pds.4375. Epub 2018 Jan 10.

Prospective surveillance pilot of rivaroxaban safety within the US Food and Drug Administration Sentinel System.

Author information

1
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA.
2
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
3
Kaiser Permanente Northern California, Oakland, CA, USA.
4
Biostatistics Unit, Group Health Research Institute and Department of Biostatistics, University of Washington, Seattle, WA, USA.
5
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
6
Center for Biologics Evaluation and Research, US Food and Drug, Rockville, MD, USA.
7
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
8
Division of Biometric VII, Office of Biostatistics, Office of Translation Sciences, US Food and Drug Administration, Silver Spring, MD, USA.
9
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
10
Optum Epidemiology, Waltham, MA, USA.
11
Aetna, Blue Bell, PA, USA.
12
Humana Inc. Louisville, KY, USA.
13
HealthCore Inc. Alexandria, VA, USA.

Abstract

PURPOSE:

The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance.

METHODS:

In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods.

RESULTS:

Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71).

CONCLUSIONS:

This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety.

KEYWORDS:

anticoagulants; outcome assessment; pharmacoepidemiology; post-marketing; product surveillance

PMID:
29318683
DOI:
10.1002/pds.4375

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