847
views
1
recommends
+1 Recommend
1 collections
    2
    shares

      CVIA now indexed by SCOPUS from February 2024. CVIA received its first Journal Impact Factor (0.5) in the 2023 Journal Citation Reports Release. 

      Interested in becoming a CVIA published author?

      • Platinum Open Access with no APCs. 
      • Fast peer review/Fast publication online after article acceptance.

      Submissions should be made electronically at: https://mc04.manuscriptcentral.com/cvia-journal.

      Please refer to the Author Guidelines at https://cvia-journal.org/instructions-to-authors/ before submission.

       

      scite_
       
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comparison of the Safety and Efficacy of Warfarin Versus Rivaroxaban in Northern Chinese Patients with Different CHA2DS2-VASc Scores: A Retrospective Cohort Study

      research-article
      Bookmark

            Abstract

            Purpose: This study was aimed at evaluating the safety and efficacy of warfarin versus rivaroxaban in patients with atrial fibrillation (AF) and different CHA2DS2-VASc score subgroups in northern China.

            Methods: A retrospective cohort study was conducted to evaluate 387 patients with AF who received treatment at our institution between September 2018 and August 2019. The patients were divided into two groups receiving either warfarin (n=194) or rivaroxaban (n=193). Follow-up data were collected, including adherence, bleeding and ischemic stroke events.

            Results: The group receiving rivaroxaban showed better adherence than the group receiving warfarin. In the warfarin-treated group, bleeding incidents declined with increasing scores. In the warfarin-treated group, patients with scores of 2–3 had greater adherence and fewer stroke occurrences. The events of bleeding and stroke did not significantly differ in patients in the rivaroxaban-treated group with different scores.

            Conclusions: Compared with patients in the warfarin group with different CHA2DS2-VASc scores, those in the rivaroxaban group had greater compliance, and fewer bleeding and stroke events. Regardless of economic considerations, rivaroxaban is preferable for anticoagulative AF treatment in northern Chinese patients.

            Main article text

            Introduction

            Atrial fibrillation (AF) is a common arrhythmia, and many independent risk factors that predispose individuals to a variety of complications, such as ischemic stroke (IS) have been reported; moreover, AF is a major cause of stroke [15]. Because of the cold weather, the incidence of AF, IS and other cardiovascular diseases is very high in northern China [6, 7]. Therefore, AF treatment has attracted substantial attention. Warfarin has been demonstrated to successfully prevent stroke in patients with AF [810]. However, the use of warfarin in patients is restricted because of the risk of bleeding incidents [11]. Numerous studies have shown that new oral anticoagulation agents (NOACs) are more effective than warfarin in preventing stroke in patients with non-valvular AF [12, 13]. The CHA2DS2-VASc score is generally used to evaluate the risk of IS in patients with AF. However, limited real-world evidence is available regarding the risk of IS according to CHA2DS2-VASc scores in northern Chinese patients [14]. In this retrospective, single-institution cohort study, we aimed to use real-world data to evaluate the incidence of bleeding and IS events in northern Chinese patients with AF treated with warfarin or rivaroxaban, according to their relative adherence and CHA2DS2-VASc scores.

            Methods

            Study Design and Patients

            In our hospital database, we conducted a retrospective review of patients with non-valvular AF who were hospitalized at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) between September 2018 and August 2019. Patients received oral anticoagulant therapy (216 patients received warfarin and 211 patients received rivaroxaban) for the prevention of IS. Patients taking anticoagulants for vein thrombosis treatment were excluded. According to physicians’ recommendations, all patients received either rivaroxaban (15–20 mg/day) or warfarin (1.25–2.5 mg/day, INR: 2.0–3.0). The study protocol was approved by the Second Affiliated Hospital of Harbin Medical University (KY2020-195).

            Safety and Efficacy Assessments

            Bleeding incidents such as hemorrhinia, fundus hemorrhage, gingival bleeding and gastrointestinal bleeding were included in the safety outcomes. The efficacy outcome was identified according to thrombosis events. IS was defined as a focal neurological deficit for 24 h with no hemorrhage. Systemic embolism was defined as acute vascular occlusion. Bleeding and IS were diagnosed by physicians through radiological examination or vascular imaging. All medical records of the patients were evaluated by a physician.

            Follow-up and Outcomes

            Clinical information on the participants in this study was collected from outpatient medical records, hospitalization medical records or telephone questionnaires. The median follow-up time was 11.2 months in the warfarin-treated group and 9.7 months in the rivaroxaban-treated group. During the follow-up visits, patients’ clinical condition, medication compliance, bleeding incidents (such as hemorrhinia, fundus hemorrhage, gingival bleeding and gastrointestinal bleeding), risk of stroke and other adverse effects were evaluated. The results in the groups treated with rivaroxaban and warfarin were compared.

            Statistical Analysis

            The CHA2DS2-VASc score was used to evaluate stroke risk. Warfarin- and rivaroxaban-treated patients were further divided into three groups with CHA2DS2-VASc scores of 0–1, 2–3 and ≥4, according to a previous study [15]. Data are shown as mean ± SEM and were compared with independent-samples t-tests for continuous variables. Data are shown as percentages and were compared with the chi-square test for categorical variables. All statistical assessments were conducted in SPSS 20 (SPSS, USA). P<0.05 was considered to indicate statistical significance.

            Results

            Study Population

            A total of 427 patients with AF who received anticoagulant therapy with warfarin or rivaroxaban were enrolled in the study. One group (216 participants) was treated with warfarin, and the other group (211 participants) was treated with rivaroxaban. A total of 40 participants were lost during the follow-up period: 22 in the warfarin-treated group and 18 in the rivaroxaban-treated group. The two groups were comparable in aspects including age, sex, hypertension, diabetes mellitus, previous stroke, cardiac function, CHA2DS2-VASc score and blood biochemical indexes (Table 1). The mean CHA2DS2-VASc scores were similar between the warfarin- and rivaroxaban-treated groups (2.75 ± 1.44 versus 2.90 ± 1.77, respectively). The median age was 61.75 ± 9.83 years and 64.90 ± 11.81 years in the warfarin-treated and rivaroxaban-treated groups, respectively. Moreover, 55.2% and 58.0% of patients were male in the warfarin-treated and rivaroxaban-treated groups, respectively.

            Table 1

            Baseline Characteristics of the Study Population.

            CharacteristicWarfarin (n = 194)Rivaroxaban (n = 193)P-value
            Age (years)61.75 ± 9.8364.90 ± 11.810.005
            Men (%)107 (55.2%)112 (58.0%)0.568
            Hypertension (%)68 (35.1%)95 (49.2%)0.005
            Diabetes mellitus (%)30 (15.5%)40 (20.7%)0.179
            Previous stroke/TIA (%)31 (16.0%)35 (18.1%)0.573
            Heart failure (%)126 (64.9%)45 (23.3%)<0.001
            Vascular disease (%)87 (44.8%)118 (61.1%)0.001
            CHA2DS2-VASc score (mean)2.75 ± 1.442.90 ± 1.770.348
            Smoking (%)52 (26.8%)35 (18.1%)0.041
            Alcohol use (%)37 (19.1%)24 (12.4%)0.073
            LDL-C (mmol/L)2.59 ± 0.852.33 ± 0.730.001
            HDL-C (mmol/L)1.11 ± 0.321.09 ± 0.250.590
            Total cholesterol (mmol/L)4.20 ± 1.033.98 ± 0.870.033
            Triglyceride (mmol/L)1.55 ± 0.711.72 ± 1.160.089
            Lipoprotein (a) (g/L)1.12 ± 0.241.17 ± 0.260.062
            Lipoprotein (b) (g/L)0.90 ± 0.260.81 ± 0.230.001
            Uric acid (μmol/L)393.31 ± 137.17342.82 ± 122.61<0.001
            Crcl (mL/min)96.83 ± 46.5190.49 ± 31.510.118
            LAD (mm)45.98 ± 9.9840.16 ± 6.38<0.001
            LVEF (%)55.34 ± 10.7558.83 ± 8.200.001
            CHA2DS2-VASc scores (%)0.0028
            0–137 (19.07)49 (25.39)
            2–3104 (53.61)70 (36.27)
            ≥453 (27.32)74 (38.34)
            Bleeding (%)30 (15.46)26 (13.47)0.5775
            Stroke (%)15 (7.73)12 (6.22)0.5588

            Data are presented as mean ± standard deviation or proportions. TIA, transient ischemic attack; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; Crcl, creatinine clearance; LAD, left atrial diameter; LVEF, left ventricular ejection fraction.

            With bleeding events and stroke events as the dependent variables, and the baseline characteristics of the study population, such as age, hypertension and heart failure, as the independent variables, the statistically significant differences in the univariate analysis were subjected to multivariate logistic regression analysis (Tables 2 and 3). LDL-C was found to be an independent risk factor for stroke events (OR=11.95, 95% confidence interval of the OR values: 1.144–124.804, P=0.0382).

            Table 2

            Multivariate Logistic Regression Analysis of Bleeding Events.

            VariateβSeWald χ2 P valueOR (95% CI)
            Group (two groups of drugs)0.14610.37940.14820.70031.157 (0.55, 2.435)
            Age−0.02770.01842.26870.1320.973 (0.938, 1.008)
            Hypertension0.30760.35020.77160.37971.36 (0.685, 2.702)
            Heart failure0.28670.44580.41340.52021.332 (0.556, 3.191)
            Vascular disease0.10730.37230.0830.77321.113 (0.537, 2.309)
            Smoking−0.61930.45641.84130.17480.538 (0.22, 1.317)
            LDL-C−0.34210.59150.33460.5630.71 (0.223, 2.264)
            Total cholesterol0.19780.47830.17110.67921.219 (0.477, 3.112)
            Lipoprotein (b)−0.25012.20030.01290.90950.779 (0.01, 58.113)
            Uric acid−0.000860.001550.30630.580.999 (0.996, 1.002)
            LAD0.01070.02450.18970.66321.011 (0.963, 1.06)
            LVEF0.002870.02130.0180.89321.003 (0.962, 1.046)
            Table 3

            Multivariate Logistic Regression Analysis of Stroke Events.

            VariateβSeWald χ2 POR (95% CI)
            Group (two groups of drugs)−1.13890.55934.14590.04170.32 (0.107, 0.958)
            Age−0.003890.02780.01950.8890.996 (0.943, 1.052)
            Hypertension0.67630.521.69170.19341.967 (0.71, 5.45)
            Heart failure−0.54050.67730.63690.42480.582 (0.154, 2.197)
            Vascular disease0.37920.54460.4850.48621.461 (0.503, 4.248)
            Smoking−0.77270.67951.29350.25540.462 (0.122, 1.749)
            LDL-C2.48071.1974.29510.038211.95 (1.144, 124.804)
            Total cholesterol−0.89830.83421.15980.28150.407 (0.079, 2.089)
            Lipoprotein (b)−4.97273.6221.88490.16980.007 (0.001, 8.384)
            Uric acid−0.00090.002290.15420.69460.999 (0.995, 1.004)
            LAD−0.01760.03590.2410.62350.983 (0.916, 1.054)
            LVEF−0.002480.0340.00530.94180.998 (0.933, 1.066)
            Adherence

            As shown in Table 4, the adherence rate was 59.3% in the warfarin-treated group, which was lower than the 78.2% in the rivaroxaban-treated group (P<0.001). The adherence rate of patients with moderate risk of stroke (score 2–3, 67.3%) was higher than those in patients with low or high risk of stroke in the warfarin-treated group (score 0–1, 51.4%; score ≥4, 49.1%). The adherence rates were similar in rivaroxaban-treated patients with different CHA2DS2-VASc scores (score 0–1, 79.6%; score 2–3, 75.7%; score ≥4, 79.7%). Lower adherence was observed in patients with scores of 0–1 and ≥4 in the warfarin-treated group than the rivaroxaban-treated group (P<0.01 for all comparisons).

            Table 4

            Adherence to Warfarin and Rivaroxaban.

            CharacteristicWarfarin (n = 194)Rivaroxaban (n = 193)P value
            All115 (59.3%)151 (78.2%)<0.001
            CHA2DS2-VASc score 0 or 119 (51.4%)39 (79.6%)0.006
            CHA2DS2-VASc score 2 or 370 (67.3%)53 (75.7%)0.232
            CHA2DS2-VASc score ≥426 (49.1%)59 (79.7%)<0.001

            CHA2DS2-VASc, risk based on the presence of congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease and sex.

            Safety and Efficacy Outcomes

            The safety and efficacy outcomes of the two groups during the follow-up period are shown in Figure 1. More bleeding events were observed in the warfarin-treated group (36, 18.6%) than the rivaroxaban-treated group (29, 15.0%), but a statistical difference was not observed (Figure 1A). A total of 36 patients experienced bleeding in the warfarin group, including hemorrhinia (12, 33.3%), fundus hemorrhage (4, 11.1%), gingival bleeding (16, 44.4%) and gastrointestinal bleeding (4, 11.1%) (Figure 1C). Moreover, 29 patients experienced bleeding in the rivaroxaban group, including hemorrhinia (3, 10.3%), fundus hemorrhage (5, 17.2%), gingival bleeding (17, 58.6%) and gastrointestinal bleeding (4, 13.8%) (Figure 1D). The cumulative incidence of IS events in the warfarin and rivaroxaban groups was 8.8% (17/194) and 6.7% (13/193), respectively (Figure 1B). No statistical difference was observed between treatment groups.

            Figure 1

            Efficacy and Safety Outcomes According to Warfarin or Rivaroxaban Treatment.

            (A) Bleeding events after warfarin or rivaroxaban treatment. (B) Ischemic stroke with warfarin or rivaroxaban treatment. Sites of bleeding with warfarin (C) or rivaroxaban (D).

            Risks of Bleeding and IS According to CHA2DS2-VASc Score

            To evaluate the safety and efficacy of warfarin versus rivaroxaban in patients with AF with different CHA2DS2-VASc scores, we classified the patients with AF into three groups with CHA2DS2-VASc scores of 0–1, 2–3 and ≥4, who were treated with warfarin or rivaroxaban. More bleeding events were observed in the warfarin-treated group than the rivaroxaban-treated group among patients with scores of 0–1 and 2–3, but the difference was not significant (Figure 2A). Furthermore, in the warfarin- or rivaroxaban-treated group, bleeding did not significantly differ among patients with different scores (Figure 2B–C).

            Figure 2

            Incidence Rates of Bleeding and Ischemic Stroke According to CHA2DS2-VASc Score.

            (A) Bleeding after warfarin and rivaroxaban treatment, according to CHA2DS2-VASc score. Bleeding after warfarin (B) or rivaroxaban (C) treatment, according to CHA2DS2-VASc score. (D) IS after warfarin or rivaroxaban treatment, according to CHA2DS2-VASc score. IS after warfarin (E) or rivaroxaban (F) treatment, according to CHA2DS2-VASc score.

            More IS events were observed among patients with scores of 0–1 and ≥4 in the warfarin-treated group than the rivaroxaban-treated group, but the difference was not statistically significant (Figure 2D). Furthermore, in the warfarin-treated group, patients with scores ≥4 had more IS events than patients with scores of 2–3 (Figure 2E) (P<0.05). In the rivaroxaban-treated group, IS events did not significantly differ among patients with different scores (Figure 2F).

            To further study the type of bleeding according to the CHA2DS2-VASc scores, we divided the bleeding patients into four subgroups with hemorrhinia, fundus hemorrhage, gingival bleeding or gastrointestinal bleeding induced by warfarin or rivaroxaban (Figure 3). Only hemorrhinia was greater in the warfarin-treated group than the rivaroxaban-treated group, among patients with scores of 0–1 (Figure 3A, P=0.018). The incidence rates of fundus hemorrhage, gingival bleeding and gastrointestinal bleeding did not significantly differ between the warfarin- and rivaroxaban-treated groups, among patients with different scores (Figure 3B–D).

            Figure 3

            Subgroups of Bleeding after Warfarin and Rivaroxaban Treatment, According to CHA2DS2-VASc Score.

            (A) Hemorrhinia, (B) fundus hemorrhage, (C) gingival bleeding and (D) gastrointestinal bleeding.

            Hospitalization

            A total of 99 patients were hospitalized in the follow-up period. The incidence rates of hospitalization were 23.2% (45/194) in the warfarin-treated group and 28.0% (54/193) in the rivaroxaban-treated group (Figure 4A). The incidence rates of hospitalization did not significantly differ in the warfarin- or rivaroxaban-treated groups, among patients with different scores (Figure 4B).

            Figure 4

            Incidence Rate of Hospitalization.

            (A) Incidence rate of hospitalization after warfarin and rivaroxaban treatment. (B) Incidence rate of hospitalization, according to CHA2DS2-VASc score.

            Discussion

            AF, which is among the most prevalent and dangerous clinical arrhythmias, poses a substantial risk to human health [1]. Oral anticoagulant drugs currently play an important role in the anticoagulant treatment of patients with AF [16]. Warfarin is a classical anticoagulant that is the most widely used in clinical practice. It is a coumarin anticoagulant that has anticoagulant and antiplatelet aggregation functions through competing with the action of vitamin K in the liver, inhibiting the synthesis of clotting factors in liver cells and decreasing of the thrombin-induced platelet aggregation reaction [17]. Although warfarin has high anticoagulant efficiency, the effective dose of warfarin varies among individuals, thus requiring frequent blood monitoring of patients to adjust the effective dose of warfarin, as well as cumbersome treatment procedures, and effects of food or drug interactions that can significantly decrease clinical benefit [18]. Rivaroxaban is a new anticoagulant that directly inhibits factor Xa, blocks endogenous and exogenous clotting pathways and inhibits thrombin production and thrombosis. Rivaroxaban is a dose-dependent inhibitor of factor Xa activity, and it has the advantages of being safe, effective and convenient for the prevention and treatment of thromboembolic diseases [19].

            Our study performed a retrospective analysis to compare the safety and efficacy of warfarin versus rivaroxaban in northern Chinese patients with AF with different CHA2DS2-VASc scores. The following conclusions were drawn from the present study: (1) Adherence was better in the rivaroxaban-treated group than the warfarin-treated group. (2) Bleeding events decreased with increased scores in the warfarin-treated group: patients with scores of 2–3 had relatively better adherence and fewer stroke events in the warfarin-treated group. (3) The events of bleeding and stroke did not significantly differ among patients with different scores in the rivaroxaban-treated group.

            In our current investigation, the risks of bleeding events were relatively high. Previous studies have indicated that warfarin and rivaroxaban pose similar risks of major bleeding [2022]. A previous study has also reported significant bleeding in 10.1% and 16.4% of patients in the warfarin and NOAC groups, respectively [23]. Our study indicated fewer bleeding events in the rivaroxaban-treated group (15.0%) than the warfarin-treated group (18.6%), but no significant difference was observed. More bleeding events were observed in the warfarin-treated group than the rivaroxaban-treated group, among patients with scores of 0–1 and 2–3, but the difference was not significant (Figure 2A). Furthermore, patients in the warfarin-treated group with scores of 0–1 had higher bleeding risk than those with scores of 2–3 and ≥4, but the difference also was not significant (Figure 2B). These results indicated that patients with AF with scores of 0–1 might experience bleeding induced by warfarin. This result is not consistent with previous findings [24] indicating high rates of bleeding events in patients with scores ≥5.

            In the present study, the incidence rate of IS was high. Previous studies have found similar stroke rates between the NOAC and warfarin-treated groups [2527]. In our study, the IS risk in the warfarin-treated group was higher than that in the rivaroxaban-treated group, among patients with scores of 0–1 and ≥4, but the difference was not significant (Figure 2D). Furthermore, in the warfarin-treated group, patients with scores of 2–3 had fewer IS events than patients with scores of 0–1 and ≥4 (Figure 2E). These results might have been due to the relatively higher adherence to treatment with warfarin in patients with scores of 2–3 (Table 4).

            Oral anticoagulants are usually used for preventing thrombosis in patients with AF before the onset of symptoms; consequently, adherence to oral anticoagulants in patients with AF is poor. One reason why patients do not adhere to their prescription regimens is that regular monitoring is necessary when warfarin is used. Numerous studies have suggested that long-term adherence to warfarin therapy is quite challenging for patients [28, 29]. Our findings, which were in line with earlier research, showed a low incidence of warfarin adherence [30]. The drug limitations of VKA and the significant benefits of fixed dosages are overcome to some extent by NOACs. Our data, which indicated higher adherence to rivaroxaban than warfarin, are similar to those from previous studies indicating high adherence to NOACs [31]. This study has several limitations, as follows: (1) retrospective data and analysis were used; (2) the follow-up time was relatively short; (3) the number of patients with AF in the analysis was relatively small; (4) the causes of nonadherence were not assessed; and (5) Cox regression models were not used, owing to the lack of an accurate time point for bleeding and stroke. In future studies, survival analyses with large cohorts should be conducted to supplement and validate the current findings.

            Conclusions

            According to the results of the safety and efficacy clinical profiles for warfarin and rivaroxaban among northern Chinese patients with AF with different CHA2DS2-VASc scores, better adherence and lower bleeding and thrombosis events were observed in the rivaroxaban-treated group than the warfarin-treated group. Thus, rivaroxaban is a better choice for northern Chinese patients receiving anticoagulative treatment for AF, regardless of economic factors.

            Acknowledgments

            Not applicable.

            Ethics approval consent to participate

            This study was reviewed by the Second Affiliated Hospital of Harbin Medical University (KY2020-195). Informed consent was not applicable.

            Consent for publication

            All authors have given their consent for the manuscript to be published.

            Availability of data and materials

            The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request.

            Conflicts of interest

            There are no conflicts of interest to declare.

            Authors’ contributions

            Conception and design: Shiwei Xu, Qi Zhao, Yuanyuan Guo. Data analysis and interpretation: Haiyu Zhang, Xianghui Li, Jing Lu, Hongyan Wang. Manuscript writing: Shiwei Xu, Zengxiang Dong. Final approval of manuscript: Zengxiang Dong.

            Citation Information

            References

            1. , . Atrial fibrillation, cognitive decline, and dementia: an epidemiologic review. Curr Epidemiol Rep 2018;5(3):252–61.

            2. , , , , , , et al. Frailty and atrial fibrillation: a systematic review. Eur J Intern Med 2018;56:33–8.

            3. , , , . Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHA2DS2-VASc score. J Am Coll Cardiol 2015;65(14):1385–94.

            4. , , , , , , et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol 2012;11(4):315–22.

            5. , , . Atrial fibrillation and silent stroke: links, risks, and challenges. Vasc Health Risk Manag 2016;12(2):65–74.

            6. , , , , , , et al. Prevalence and relative risk factors of atrial fibrillation in male coal miners in North China. Int J Cardiol 2014;174(1):223–4.

            7. , , , , , , et al. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation 2017;135(8):759–71.

            8. , , . Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146(12):857–67.

            9. , , , , , , et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370(9586):493–503.

            10. , , , , , , et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151(5):297–305.

            11. , , , , . Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115(21):2689–96.

            12. , , , , , , et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139–51.

            13. , , , , , , et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365(10):883–91.

            14. , , , , , , et al. CHA2DS2-VASc and R2CHA2DS2-VASc scores predict mortality in high cardiovascular risk population. Eur J Clin Invest 2022;52(11):e13830.

            15. , , , , , , et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc 2016;5(2):e003074.

            16. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; , , , , , et al. Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31(19):2369–429.

            17. , , . The influence of excessive consumption of liquorice on phenprocoumon (Marcumar®): a case report. J Int Med Res 2021;49(11):3000605211049649.

            18. , , , , , . Direct medical cost of stroke and the cost-effectiveness of direct oral anticoagulants in atrial fibrillation-related stroke: a cross-sectional study. Int J Environ Res Public Health 2022;19(3):1078.

            19. , . A Cohort study on the safety and efficacy of warfarin and rivaroxaban in anticoagulant therapy in patients with atrial fibrillation study. Biomed Res Int 2022;2022:4611383.

            20. EINSTEIN–PE Investigators, , , , , , et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366(14):1287–97.

            21. EINSTEIN Investigators, , , , , , et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363(26):2499–510.

            22. , , , , , , et al. Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation). J Am Coll Cardiol 2014;63(9):891–900.

            23. , , , , , . Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation. J Geriatr Cardiol 2016;13(7):566–72.

            24. , , , , , , et al. The CHA2DS2-VASc score predicts major bleeding in non-valvular atrial fibrillation patients who take oral anticoagulants. J Clin Med 2018;7(10):338.

            25. , , , , , , et al. Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial. Stroke 2014;45(6):1739–47.

            26. , , , , , , et al. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013;44(7):1891–6.

            27. , , , , , , et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –. Circ J 2012;76(9):2104–11.

            28. , , , . Impact of adherence, knowledge, and quality of life on anticoagulation control. Ann Pharmacother 2005;39(4):632–6.

            29. , , , , , , et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010;3(6):624–31.

            30. , . Adherence to warfarin treatment among patients with atrial fibrillation. Clin Res Cardiol 2014;103(12):998–1005.

            31. , , , , , , et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration. Am Heart J 2014;167(6):810–7.

            Author and article information

            Journal
            CVIA
            Cardiovascular Innovations and Applications
            CVIA
            Compuscript (Ireland )
            2009-8782
            2009-8618
            24 May 2023
            : 8
            : 1
            : e985
            Affiliations
            [1] 1Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, 148 Baojian Road, Nangang District, Harbin, 150001, China
            [2] 2Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China
            [3] 3The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China
            [4] 4Department of Geriatrics, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China
            [5] 5NHC Key Laboratory of Cell Transplantation, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China
            Author notes
            Correspondence: Zengxiang Dong, The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province and NHC Key Laboratory of Cell Transplantation, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China, E-mail: dongzx1982@ 123456163.com ; and Yuanyuan Guo, Department of Geriatrics, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China, E-mail: guoyuanyuan@ 123456hrbmu.edu.cn

            aShiwei Xu and Qi Zhao contributed equally to this work.

            Article
            cvia.2023.0030
            10.15212/CVIA.2023.0030
            487ef6d4-de77-4d20-91bd-da7a4c64d95a
            Copyright © 2023 Cardiovascular Innovations and Applications

            This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 Unported License (CC BY-NC 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc/4.0/.

            History
            : 08 January 2023
            : 26 March 2023
            : 27 April 2023
            Page count
            Figures: 4, Tables: 4, References: 31, Pages: 10
            Funding
            Funded by: National Natural Science Foundation of China
            Award ID: 81900366
            Funded by: Postdoctoral Initiation Foundation of Heilongjiang Province
            Award ID: LBH-Q19032
            Funded by: Research Project of the First Affiliated Hospital of Harbin Medical University
            Award ID: 2021J01
            The study was funded by the National Natural Science Foundation of China (No. 81900366), the Postdoctoral Initiation Foundation of Heilongjiang Province (LBH-Q19032) and the Research Project of the First Affiliated Hospital of Harbin Medical University (2021J01).
            Categories
            Research Article

            General medicine,Medicine,Geriatric medicine,Transplantation,Cardiovascular Medicine,Anesthesiology & Pain management
            Ischemic stroke,Rivaroxaban,CHA2DS2-VASc score,Warfarin,Atrial fibrillation

            Comments

            Comment on this article