Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta‐Analysis

Abstract

Background Evidence on the differences in fracture risk associated with non‐vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta‐analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random‐effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77–0.91; P <0.001) with low heterogeneity ( I 2 =38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81–0.98; P =0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54–1.01; P =0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real‐world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.

The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density

“…However, a significant association between the use of vitK antagonists and fracture risk was reported in females and in the elderly. Recently, two meta-analyses have reported that the use of direct and non-vitK oral anticoagulants, such as rivaroxaban and apixaban, was associated with a lower risk of fractures when compared to the use of warfarin [ 369 , 370 ], indicating that it might be better to choose for a direct oral anticoagulant in individuals at high risk for fractures.…”

Potential Application of Recombinant Snake Prothrombin Activator Ecarin in Blood Diagnostics

“…Fondaparinux is used to prevent blood clots forming in patients who are recovering from orthopedic or abdominal surgery [ 33 ], while rivaroxaban functions to treat and prevent deep venous thrombosis (DVT) [ 34 ]. In addition, apixaban enables blood to flow through a patient’s veins more easily to prevent dangerous blood clot formation [ 35 ]. In these experiments, both Fondaparinux and apixaban were spiked into citrated blood, with a range of 0–4 µg/mL, and rivaroxaban with a range of 0–20 µg/mL ( Figure 6 ).…”

The interplay between bone and heart health as reflected in medication effects: A narrative review

“…Even in the absence of compelling data to support warfarin avoidance in patients with metabolic bone disease, such as osteoporosis, warfarin’s effects may still be important to consider when choosing anticoagulant. In their meta-analysis of studies of fracture in warfarin and non-VKA oral anticoagulants, Huang et al 94 discovered that the warfarin-treated group had a higher risk of fracture than the other anticoagulant groups. These findings have been echoed in other meta-analyses, 95 including a meta-analysis assessing fractures among subjects treated with VKA and various direct oral anticoagulants (DOACs), which found that the risk of osteoporotic fracture was greatest in groups treated with VKA versus DOACs.…”