PMID- 35776157
OWN - NLM
STAT- MEDLINE
DCOM- 20220812
LR  - 20221005
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 78
IP  - 9
DP  - 2022 Sep
TI  - Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data 
      from VigiBase.
PG  - 1521-1526
LID - 10.1007/s00228-022-03357-4 [doi]
AB  - PURPOSE: The aim of this study was to analyze the clinical characteristics of 
      fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline 
      the importance of the rational use of drugs. METHODS: The WHO global database of 
      reported potential side effects of medicinal products (VigiBase) was searched for 
      fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical 
      characteristics of those cases with sufficient information (vigiGrade 
      completeness score >/= 0.80) were analyzed. RESULTS: By January 19, 2020, 2309 
      fatal adverse event reports of rivaroxaban combined with aspirin from 21 
      countries were entered in VigiBase. One hundred and twenty cases contained 
      further information, of which 42 were female (35%) and 78 were male (65%). The 
      median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly 
      patients (>/= 65 years). The AEs listed in the fatal case reports included bleeding 
      in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 
      and 46 respectively, accounting for 88%) and ischemic events in six cases 
      (ischemic stroke in three, acute myocardial infarction in two, myocardial 
      infarction combined with acute liver failure in one). Among the patients with 
      bleeding events, 108 (95%) had existing risk factors for bleeding or for 
      interacting with aspirin or rivaroxaban. These may be divided into the following: 
      diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or 
      previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, 
      P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, 
      steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., 
      elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). 
      There were 45 cases with two or more of these risk factors in addition to 
      rivaroxaban and aspirin. Patients with ischemic events are often in very 
      high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or 
      self-discontinuation of treated drugs. Medication errors occurred in 24 patients 
      (20%): excessive treatment in 17 cases, contraindication in three, frequency 
      error in two, excessive treatment combined with contraindication in one, and 
      self-discontinuation in one. CONCLUSIONS: Fatal AEs related to rivaroxaban 
      combined with aspirin, including bleeding and ischemic events, have been reported 
      mostly in the elderly, and sometimes involved medication errors. The fatal AEs 
      mainly manifested as serious bleeding, and most of them occurred in patients with 
      concurrent multiple risk factors. Monitoring coagulation during rivaroxaban 
      treatment is recommended in very high-risk ASCVD populations, and attention 
      should be paid to prevention of medication errors.
CI  - (c) 2022. The Author(s).
FAU - Zhang, Qingxia
AU  - Zhang Q
AUID- ORCID: 0000-0002-3843-8767
AD  - Department of Pharmacy, National Clinical Research Center for Geriatric Disease, 
      Xuanwu Hospital Capital Medical University, Beijing, China. WL7322681@sina.com.
FAU - Ding, Qian
AU  - Ding Q
AUID- ORCID: 0000-0001-5323-9996
AD  - School of Pharmaceutical Science, Capital Medical University, Beijing, China.
FAU - Yan, Suying
AU  - Yan S
AD  - Department of Pharmacy, National Clinical Research Center for Geriatric Disease, 
      Xuanwu Hospital Capital Medical University, Beijing, China.
FAU - Yue, Qun-Ying
AU  - Yue QY
AUID- ORCID: 0000-0003-2475-2621
AD  - Uppsala Monitoring Centre, Uppsala, Sweden. qun-ying.yue@who-umc.org.
LA  - eng
PT  - Journal Article
DEP - 20220701
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 9NDF7JZ4M3 (Rivaroxaban)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aspirin/therapeutic use
MH  - Factor Xa Inhibitors/therapeutic use
MH  - Female
MH  - Hemorrhage/chemically induced/epidemiology
MH  - Humans
MH  - Ischemia/chemically induced
MH  - Male
MH  - *Myocardial Infarction/drug therapy
MH  - Platelet Aggregation Inhibitors/therapeutic use
MH  - *Rivaroxaban/therapeutic use
PMC - PMC9365742
OTO - NOTNLM
OT  - Adverse drug events
OT  - Aspirin
OT  - Fatal
OT  - Medication errors
OT  - Rivaroxaban
OT  - VigiBase
COIS- The authors declare no competing interests.
EDAT- 2022/07/02 06:00
MHDA- 2022/08/13 06:00
PMCR- 2022/07/01
CRDT- 2022/07/01 11:13
PHST- 2022/02/14 00:00 [received]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/07/02 06:00 [pubmed]
PHST- 2022/08/13 06:00 [medline]
PHST- 2022/07/01 11:13 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 10.1007/s00228-022-03357-4 [pii]
AID - 3357 [pii]
AID - 10.1007/s00228-022-03357-4 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2022 Sep;78(9):1521-1526. doi: 10.1007/s00228-022-03357-4. 
      Epub 2022 Jul 1.