(286) Risk of Adverse Events Associated with Novel Oral Anticoagulant (Apixaban): A Systematic Review and Meta-Analysis

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 617

Presenting Author(s)

Amar Ashok Maske, M.Pharmacy
– Student, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Tembhurni, Maharashtra, India

Co-Author(s)

Christy Thomas
– National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Guwahati, Assam, India
Krishna Undela, MPharm, PhD
– Assistant Professor, National Institute of Pharmaceutical Education and Research,Guwahati, Guwahati, Assam, India

Background: Novel oral anticoagulant (NOACs) is now frequently used in patients with atrial fibrillation (AF), venous thromboembolism (VTE), VTE prophylaxis, stroke prevention, valve disorders, and cardiovascular diseases (CVD). In recent years, safety alerts have been issued due to the risk of adverse events associated with NOACs. The safety signals raised in term of bleeding-related adverse events of NOACs is still controversial.

Objectives: 1. To evaluate the risk of adverse events associated with NOACs in patients with various indications such as AF, VTE, VTE prophylaxis, stroke, and CVD.
2. To estimate the ranking and hierarchy of interventions based on the safety of NOACs.

Methods: We searched electronic databases such as PubMed, Google Scholar, and Cochrane CENTRAL database from its inception to 20 December 2021. The key search terms used were (“NOAC” OR “DOACs” OR “NON-VITAMIN K ANTAGONIST” OR “TOACs” OR “NOVEL ORAL ANTICOAGULANTS” OR “APIXABAN” OR “ELIQUIS”) AND (“AF” OR “VTE” OR “STROKE” OR “CVD”). All randomized controlled trials (RCTs investigate the risk of adverse events as a safety outcome, such as intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB0, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) of NOACs in comparison with placebo or active comparators such as vitamin K anticoagulants (VKAs), low molecular weight of heparin (LMWHs), aspirin were included in the study. Statistical heterogeneity and P value were calculated using the I2 statistics and Cochran’s Q test. We performed the NMA, and the surface under the cumulative ranking (SUCRA) curve was constructed using 'R' software, version 4.2.0, with the 'netmeta' package.

Results: A total of 11750 studies were initially searched and identified through a database searching were included in the study. The pooled analysis risk of GIB studies revealed a non-significant association. Edoxaban (OR=1.29, 95%CI: 1.05-1.55; P=0.009; I2=43%), Dabigatran (OR=1.16, 95%CI: 1.03-1.31; P=0.02; I2=0%), and Rivaroxaban (OR=1.61, 95%CI: 1.41-1.83; P<0.00001; I2=48%) showed significant association, its increases the risks of GIB compared to VKAs, LMWH, ASA. Risk of CRNMB, pooled analysis revealed Edoxaban (OR=0.85, 95%CI: 0.82-0.88; P<0.00001; I2=44%), Rivaroxaban (OR=1.61, 95%CI: 1.41-1.83; P<0.00001; I2=48%) having significant increase risk of CRNMB. In risks of ICH, Apixaban (OR=0.44, 95%CI: 0.41-1.33; P<0.00001; I2=0%), Edoxaban (OR=0.46, 95%CI: 0.40-0.53; P<0.00001; I2=0%), and Dabigatran (OR=0.40, 95%CI: 0.25-0.66; P= 0.0003; I2=69%) had a significant association in various indications of patients taking NOACs compared to VKAs, LMWH, ASA, and Placebo. In MB risks, Dabigatran (OR=0.81, 95%CI: 0.75-0.88; P< 0.00001; I2=14%) have a significant association with decrease in MB risk.

Conclusions: According to this systematic review and network meta-analysis, NOACs are a safer treatment for ICH as they reduce ICH risk. However, they significantly increase the risk of GIB. This NMA, which incorporates direct and indirect evidence, assigns a ranking order to all outcomes. NOACs have a statistically non-significant association with MB and CRNMB.