Meta-Analysis Evaluating the Efficacy and Safety of Low-Intensity Warfarin for Patients >65 Years of Age With Non-Valvular Atrial Fibrillation

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Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia. It is of a high disability and death rate, and seriously affects quality of life. Although New oral anticoagulants (NOACs) are recommended for anticoagulation therapy of atrial fibrillation, they are not widely used for the high cost and limited availability. Warfarin is effective and economical. The risk of thromboembolism and anticoagulant hemorrhage is higher in patients >65 years with NVAF. So, it is of great clinical significance to explore the optimal anticoagulation intensity of warfarin in patients >65 years of China, and other ethnicities. Some studies suggested that low-intensity international normalized ratio (INR) has similar antithrombotic efficacy comparing to standard-intensity INR, whereas bleeding risk was significantly reduced. But others showed conflicting results. We pooled the efficacy and safety data of low- and standard-intensity warfarin therapy for patients over 65 years with NVAF by meta-analysis, as to evaluate optimal INR intensity of warfarin therapy in patients over 65 years. We identified 18 studies providing data of 2105 patients receiving anticoagulation therapy with warfarin. On meta-analysis (odds ratio [OR] [95% confidence interval {CI}]), low-intensity INR conferred similar efficacy to standard intensity INR on all thrombosis (1.28 [0.90 to 1.81]), stroke (1.09 [0.67 to 1.77]), other thromboembolism ([peripheral and pulmonary embolism] 2.26 [0.89 to 5.79]), and all cause death (1.38 [0.94 to 2.02]). Low-intensity INR conferred better safety profile than standard intensity INR in major bleeding (intracranial and gastrointestinal hemorrhage) (0.32 [0.19 to 0.52]), minor bleeding (gum, nasal cavity and conjunctival hemorrhage, skin ecchymosis, hematuria, hemoptysis) (0.30 [0.20 to 0.45]), and all bleeding (0.30 [0.22 to 0.40]). In conclusion, low-intensity INR (1.5 to 2.0) of warfarin therapy is as effective as standard intensity INR (2.0 to 3.0) therapy in reducing thromboembolic risk in patients>65 years with NVAF, and has a safer profile of bleeding.

Section snippets

Methods

All studies reporting anticoagulation therapy of NVAF in patients >65 years published before May 2020 were identified by the comprehensive computer-based search of PubMed, Cochrane, EmBase, Web of Science, Chinese BioMedical, Global Health, and BIOSIS Previews databases. The following terms were used for search: Atrial fibrillation, nonvalvular, warfarin, anticoagulation. Hand searches for related articles were also performed. All the searches were conducted without language restriction.

Results

With separated search strategy in each database, a total of 1,029 articles that potentially pertinent were retrieved. By reviewing titles and abstracts, irrelevant studies, case reports, and reviews were excluded. Finally, 72 studies were identified for further considerations. Of these, 54 studies were further excluded mainly due to the age of patients included was less than 65 years old (53 studies), or INR ranged 1.6 to 2.5 (one study). Therefore, 18 studies including 2,105 patients (1,058 in

Discussion

NVAF is one of the most common arrhythmia in patients >65 years, which increasing the risk of stroke by 5 times. Stroke not only increases the social disability burden, but also economic burden of public health and medical system.25 It is of great significance to explore an optimal anticoagulation therapy for patients >65 years with NVAF. There have been many studies on anticoagulation therapy of AF, but patients’ age was in a broad range. Studies on populations over 65 years in this field were

Disclosure

All the authors have nothing to disclose.

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      2022, IJC Heart and Vasculature
      Citation Excerpt :

      Compared with NAT or AP, NVAF patients treated with VKA or NOAC had a better prognosis, with lower all-cause death (χ2 = 58.05, p < 0.001), lower stroke incidence (χ2 = 31.50, p < 0.001), lower CRNM GIB incidence (χ2 = 25.71, p < 0.001), and no increase in MB events (χ2 = 2.91, p = 0.406). For very elderly patients with NVAF, lower dosages of NOACs were used or lower INR target of VKA was achieved (e.g., dabigatran 110 mg twice daily, rivaroxaban 15 mg once daily, edoxaban 30 mg once daily, apixaban 2.5 mg twice daily, warfarin INR target 1.6–2.6) [10–14]. Decisions to prescribe reduced dose NOACs or low INR target VKA are made based on the specific considerations on age, weight, renal function and use of specific concomitant medications.

    Funding Sources: This work is supported by the Natural Science Foundation of Guangdong Province of China (Grant No.2016A030313794); Guangdong Provincial Bureau of traditional Chinese Medicine (Grant No.20191315); Research Fund for Compound Danshen Dripping Pills (Grant No.K0601192). The funding organizations did not have any role in the study design, collection, analysis, or interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. The researchers were independent from the funding organizations.

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