丁征
中国医学科学院阜外医院 药剂科
BACKGROUND:Non-vitamin K antagonist oral anticoagulants (NOACs) are alternative to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF). Along with their widespread clinical use in China, the off-label use of NOACs is commonly seen in real-world practice, which could result in adverse drug events and poor clinical outcomes. However, guideline adherence and label adherence for NOAC prescriptions have not been well evaluated in a real-world setting in China.METHODS:Between January 2021 and June 2021, a total of 1,750 outpatients or inpatients with AF will be consecutively enrolled at 26 canters in China. Data on patient demographics, clinical characteristics, treatment strategies, and prescribing information related to anticoagulation therapy for patients with AF will be collected. Clinical pharmacists will evaluate the rationality of the anticoagulation regimens and NOAC prescriptions based on the guideline recommendations and drug labels that are approved by the National Medical Products Administration. The primary outcomes will be the prevalence of irrational anticoagulation strategies and the inappropriate NOAC prescriptions, as well as potential risk factors associated with inappropriate prescriptions in patients with AF.DISCUSSION:This study will be the first national, multicenter, prospective study performed by pharmacists to explore real-world data on the appropriateness of NOAC prescription in Chinese patients with AF.TRIAL REGISTRATION:The Chi-NOACs-AF trial (Trial number: ChiCTR2000035908).
Annals of translational medicine 2021
BACKGROUND:Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown.OBJECTIVE:This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation.METHODS:This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes.RESULTS:A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005).CONCLUSIONS:The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR.TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):RR2-10.1136/bmjopen-2019-032949.
Journal of medical Internet research 2021
Background: Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Results: Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. Conclusions: DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
Frontiers in cardiovascular medicine 2020
BACKGROUND:Atrial fibrillation (AF) is quite prevalent in patient with chronic kidney disease (CKD). This study mainly investigated the net clinical benefit (NCB) property of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with AF and CKD by a pooled-analysis.METHODS:A comprehensive search of Medline, Embase, Cochrane Library and Clinical Trials.gov Website was performed for eligible randomized controlled trials (RCTs) reporting the efficacy and safety outcomes according to renal function of NOACs. Pre-specified outcomes and their number of patients needed to treat (NNT), including stroke/systemic embolism (SSE), major bleeding, and all-cause death, were evaluated using a random-effects model. NCB that balanced SSE and major bleeding was calculated using Singer's method.RESULTS:Four phase III clinical trials including 70,952 patients were enrolled, 45,265 (64%) with CKD, and 25,687 (36%) without CKD; 41,942 (59%) taking NOACs and 29,010 (41%) taking warfarin. Risks of SSE [relative risk (RR): 0.80, 95% confidence interval (CI): 0.73-0.88, P<0.01], major bleeding (RR: 0.79, 95% CI: 0.66-0.96, P=0.017), and all-cause death (RR: 0.91, 95% CI: 0.84-0.99, P=0.031) were significantly lower in CKD patients with NOACs than those with warfarin, accompanying with a high absolute risk reduction (NNT: 182 for SSE; 122 for major bleeding; 196 for all-cause death). While NOACs were not superior to warfarin on SSE, major bleeding, and all-cause death in patients without CKD, the NCB of NOACs versus warfarin was progressively increased with the deterioration of renal function (NCB: 0.72 for no CKD, 1.59 for mild CKD, 2.74 for moderate CKD). Sensitivity analyses did not significantly affect the primacy results.CONCLUSIONS:NOACs, compared with warfarin, provide a better clinical profile on SSE, major bleeding, all-cause death, and NCB in CKD patients.
Cardiovascular diagnosis and therapy 2019
BACKGROUND:Patients with warfarin have a potential risk of warfarin-related nephropathy, which could result in the discontinuation of anticoagulation therapy. The question of whether non-vitamin K antagonist oral anticoagulants (NOACs) use is associated with increased risk of renal impairment in atrial fibrillation (AF) patients remains unanswered.METHODS:Studies were systematically searched through Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website. Randomized controlled trials (RCTs) reporting renal impairment events and observational nationwide database studies presenting adjusted hazard ratio (HR) in AF patients with NOACs were identified. The Primacy outcome was renal impairment, defined as a composite of any renal disorder. The secondary outcomes were narrow definition of renal failure (including renal failure, acute renal failure, chronic renal failure, acute prerenal failure and postrenal failure) and individual renal impairment reported in involved studies. HR and 95% confidence intervals (95%CI) were calculated using fixed- or random-effects models according to the extent of heterogeneity. Subgroup analyses were conducted according to individual NOACs, study types and different controls.RESULTS:Totally, 189,483 patients from 11 RCTs and 3 observational database studies were included in the analysis (119,188 patients with NOACs and 70,295 patients with vitamin K Antagonists or acetylsalicylic acid). Overall results indicated a significantly lower risk of renal impairment in AF patients with NOACs versus VKAs/acetylsalicylic acid (HR: 0.67, 95%CI: 0.62-0.73). Results of narrow definition of renal impairment were accordant with the primacy outcome (HR: 0.65, 95%CI: 0.60-0.71). Compared with VKAs or acetylsalicylic acid, dabigatran (HR: 0.64, 95%CI: 0.56-0.72), rivaroxaban (HR: 0.66, 95%CI: 0.55-0.77) and apixaban (HR: 0.73, 95%CI: 0.59-0.87) were all associated with a significantly lower risk of renal impairment, with the exception of edoxaban (HR: 0.79, 95%CI: 0.30-1.27).CONCLUSIONS:Patients with NOACs might bring about a lower risk of renal impairment compared to VKA or acetylsalicylic acid. Further specialized designs of RCTs and real-world studies on evaluation of renal function are warranted to obtain a robust result on this issue.
Thrombosis research 2019
