New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof

Abstract

The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed-average international normalized ratio (INR) of 2.6-and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01-4.74) and hematoma (OR, 2.43; 95% CI, 1.39-4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28-0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09-10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs.

Anticoagulants and Osteoporosis

“…The general idea that emerges is that their use has a mild effect on any changes in bone metabolism [70,71,72,73,74,75,76,77,78] and there is no significant clinical consequence to date to the extent that they cause a reduction in bone mass or secondary osteoporosis fractures. Comparison with VKAs shows a lower risk of osteoporosis and fractures [79,80].…”

“…Treceño-Lobato et al included a total of 334 patients in a study with the aim to evaluate the adverse drug reaction (ADR) incidence rate for classic compared to new anticoagulants. The most significant result was the osteoporosis risk associated with the consumption of VKAs, with 11 cases recorded in the cohort of these patients versus none in the cohort of patients treated with DOACs, supporting the appropriateness of using DOACs in patients at risk of osteoporotic fractures [80].…”

A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation

“…The patients on unfractionated heparin had the highest fracture incidence, but DOACs had no increased fracture risk. [39,40] In another meta-analysis comparing osteoporotic fractures between VKA and DOAC, it was found that DOAC was associated with lower osteoporotic fractures than VKA in NVAF patients but not for VTE prophylaxis. [38] However, our meta-analysis results are more robust as the sample size was more significant (89,549 vs. 321,844) and comprised of extensive population-based studies.…”

“…The patients on unfractionated heparin had the highest fracture incidence, but DOACs had no increased fracture risk. [ 39 , 40 ]…”

Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran

“…In light of the aspects considered so far, it becomes crucial to detect, assess, understand, and maybe prevent all NOACs ADRs [ 26 ], not just the severe ones, but even the very rare ones, such as body rash, epistaxis, ecchymosis, gingival bleeding and other [ 27 , 28 ] or any negative drug–drug interactions [ 29 , 30 , 31 ] detected in real-world experience, considering, as discussed above, the clinical complexity of patients treated.…”