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OBJECTIVE To compare the anticoagulant effectiveness and safety of new oral anticoagulants （NOACs）and warfarin after heart valve replacement ，and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed，Cochrane Library ，Embase，Web of Science ，CNKI，Wanfang database and VIP ，clinical studies about the use of NOACs versus warfarin after heart valve replacement were collected during the inception to July 2021. After literature screening and data extrac tion，the quality of included randomized controlled trials （RCTs）were evaluat ed by bias risk assessment tool recommended by Cochrane system evaluator manual 5.2.0. After the quality of the included cohort studies was evaluated by Newcastle-Ottawa scale （NOS），RevMan 5.3 software was used for meta-analysis and sensitivity analysis. RESULTS A E-mail：carolmeng_0813@163.com total of 9 studies involving 4 962 patients were included ，of which 7 were RCTs and 2 were cohort studie s. Results of meta-analysis showed that after biological valve replacement/repair ，the incidence of stroke and systemic embolism （SSE）[OR＝0.71，95％CI（0.52，0.97），P＝0.03]，major bleeding [OR ＝0.40，95％CI （0.30，0.54），P＜0.000 01] and intracranial hemorrhage [OR ＝0.20，95％CI（0.04，0.95），P＝0.04] in trial group were significantly lower than warfarin group ；there was no significant difference in all-cause mortality between 2 groups [OR ＝1.25，95％CI（0.88， 1.79），P＝0.22]. After mechanical valve replacement/repair ，there were no significant difference in the incidence of SSE [OR ＝1.52， 95％CI（0.04，60.29），P＝0.82] or all-cause mortality [OR ＝0.26，95％CI（0.04，1.84），P＝0.18] between 2 groups. The results of subgroup analysis according to the follow-up time showed that after biological valve replacement/repair ，the incidence of SSE in trial group was significantly lower than that in control group when the follow-up time was ≤3 months [OR ＝0.20，95％CI（0.06， 0.74），P＝0.03]；but there was no significant difference in the incidence of major bleeding between 2 groups [OR ＝0.67，95％CI （0.19，2.38），P＝0.53]；when the follow-up time was longer than 3 months，there was no statistical significance in the incidence of SSE between 2 groups [OR ＝0.74，95％CI（0.54，1.02），P＝0.07]，while the incidence of major bleeding in trial group was significantly lower than control group [OR ＝0.39，95％CI（0.29，0.52），P＜0.001]. Subgroup analysis by study type showed that after biological valve replacement/repair ，the incidence of SSE in the RCT in trial group was significantly lower than that in control group [OR ＝0.51，95％CI（0.29，0.92），P＝0.03]，but there was no significant difference in the incidence of major bleeding between 2 groups[OR＝0.58，95％CI（0.33，1.03），P＝0.06]. In cohort study ，there was no significant difference in the incidence of SSE between 2 groups [OR ＝1.03，95％CI（0.40，2.66），P＝0.95]，while the incidence of major bleeding in trial group was significantly lower than control group [OR ＝0.20，95％CI（0.06，0.74），P＜0.001]. Sensitivity analysis results showed that the results of the above-mentioned meta-analysis were relatively robust. CONCLUSIONS For the patients underwent biological valve replacement/repair，the effectiveness and safety of NOACs are better than or similar to those of warfarin ；for the patients underwent mechanical valve replacement/repair ，there is no significant difference in the effectiveness and safety between NOACs and warfarin.
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OBJECTIVE: To evaluate the efficacy and safety of new oral anticoagulants (dabigatran etexilate, rivaroxaban, apixaban, edoxaban) in the treatment of non-valvular atrial fibrillation. METHODS: The randomized controlled trials about new oral anticoagulants in the treatment of non-valvular atrial fibrillation, which had been published from the time of library foundation to March 2016 were collected from Pubmed, Embase, Medline, Cochrane, ClinicalTrials.gov, Web of Science, CNKI, Wanfang database, VIP database according to the following criterias. At the same time quality of the trials was evaluated and the results of studies were analyzed using Rev Man 5.3 software and Stata 13.1 software. RESULTS: Seventeen randomized controlled trials were included, involving 83 561 patients. Network Meta-analysis showed that in the prevention of all-cause mortality, the optimal sorting order of new oral anticoagulants was rivaroxaban, apixaban, edoxaban, dabigatran etexilate; in the prevention of the incidence of stroke and systemic embolism, the optimal sorting order of new oral anticoagulants was rivaroxaban, dabigatran etexilate, apixaban, edoxaban; in the prevention of the incidence of ischemic stroke, the optimal sorting order of new oral anticoagulants was rivaroxaban, apixaban, dabigatran etexilate, edoxaban; the incidence of major bleeding for the optimal sorting order of new oral anticoagulants was edoxaban, apixaban, dabigatran etexilate, rivaroxaban; the incidence of intracranial bleeding for the optimal sorting order of new oral anticoagulants was dabigatran etexilate, edoxaban, apixaban, rivaroxaban; the incidence of myocardial infarction for the optimal sorting order of new oral anticoagulants was rivaroxaban, apixaban, edoxaban, dabigatran etexilate. The inconsistency of all the outcomes indicated that there was no significant difference between direct comparison and indirect comparison. In addition, there was no statistical heterogeneity among studies. CONCLUSION: Through analysis the effectiveness, safety and economy of new oral anticoagulants, apixaban has the best sort and should be used in preference.
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OBJECTIVE: To evaluate the efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) in the treatment of atrial fibrillation. METHODS: The randomized controlled trials of new oral anticoagulants versus warfarin in the treatment of atrial fibrillation, which had been published from the time of library foundation to May, 2015, were collected from Pubmed, Embase, Medline, Cochrane, ClinicalTrials.gov, CNKI, Wanfang database, and VIP database according to the inclusion criterias. At the same time the quality of the trials was evaluated and the results of studies were analyzed using RevMan 5.3 software and Stata 13.1 software. RESULTS: Eleven randomized controlled trials were included, involving 75 621 patients. Meta-analysis showed that compared with warfarin, the new oral anticoagulants significantly reduced the incidences of all-cause mortality [RR=0.90, 95% CI(0.85, 0.94), P<0.000 1], stroke and systemic embolism [RR=0.86, 95% CI(0.79, 0.93), P=0.0001], major bleeding [RR=0.79, 95% CI(0.74, 0.84), P<0.00001], and intracranial bleeding [RR=0.43, 95% CI(0.37, 0.51), P<0.000 01]. No differences were found in the incidence of ischemic stroke [RR=1.02, 95% CI (0.93, 1.12), P=0.71] and myocardial infarction [RR=1.02, 95% CI (0.91, 1.16), P=0.70]. Heterogeneity was lower through subgroup analysis, no publication bias was found in funnel plots of most outcomes, and sensitivity analysis indicated the results were reliable. CONCLUSION The efficacy and safety of new oral anticoagulants are better than warfarin, which may have broad prospects.
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In patients with nonvalvular atrial fibrillation (AF), the risk of stroke is five times that of patients with a normal sinus rhythm. Antithrombotic therapy has a pivotal role for the prevention of stroke. With the advent of new oral anticoagulants (NOAC), the strategy of antithrombotic therapy has undergone significant changes due to its better efficacy, safety, and convenience when compared with warfarin or an antiplatelet regimen. Furthermore, new aspects of antithrombotic therapy in the prevention of stroke have revealed that the efficacy of antiplatelet regimens is weak while the risk of major bleeding is not significantly different to that of oral anticoagulant therapy, especially in the elderly. To reflect these pivotal changes, the previous guidelines for use of NOACs have been updated in recent years by various societies and associations. The Korean Heart Rhythm Society (KHRS) summarized the current evidence and updated its recommendations for stroke prevention in patients with nonvalvular AF. First of all, antithrombotic therapy must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient, especially with regard to balancing the benefit of stroke prevention with the risk of bleeding. They recommend using the CHA2DS2-VASc score rather than the CHADS2 score to assess the risk of stroke, and suggest the HAS-BLED score be used to validate bleeding risk. In patients with truly low risks (lone AF, CHA2DS2-VASc score of 0), no antithrombotic therapy is recommended, whereas oral anticoagulant (OAC) therapy, including warfarin (INR 2-3) or NOACs, is recommended in patients with a CHA2DS2-VASc score > or = 2 unless contraindicated. In patients with a CHA2DS2-VASc score of 1, OAC therapy should be preferentially considered. When also factoring in the bleeding risk and patient preferences, antiplatelet therapy or no therapy could be the best treatment option.
Subject(s)
Aged , Humans , Anticoagulants , Atrial Fibrillation , Heart , Hemorrhage , Patient Preference , Stroke , WarfarinABSTRACT
Objectives: To synthesize the efficacy and safety outcomes from randomized-controlled trials (RCTs) regarding new oral anticoagulant, protease-activated receptor-1 (PAR-1) antagonist, and warfarin adjunctive to aspirin for patients after acute coronary syndrome (ACS) via pair-wise and network meta-analyses. Methods: A comprehensive literature search was performed in Embase, Medline, Cochrane Library Web of Knowledge, and Scopus. The pair-wise meta-analysis was undertaken respectively to each agent/treatment category via Revmen 5.1. In order to estimate the relative efficacy of each agent/treatment category whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using both fixed- and random-effects model. Covariate analysis was performed to explore the effects of length of follow-up and age of subject on the final results. Results: In total, 23 RCTs were included in the meta-analysis. As shown by the results (OR,95%CI) for the pair-wise meta-analysis, new oral anticoagulants (0.85, [0.78, 0.93] and 3.04, [2.21, 4.19]), PAR-1 antagonists (0.80, [0.52, 1.22] and 1.55, [1.25, 1.93]) and warfarin (0.87, [0.74, 1.02] and 1.77, [1.46, 2.14]) might be able to provide better outcome in the incidences of major adverse events (MAE) but with higher bleeding risk comparing to aspirin treatment alone. Based on the model fit assessment, the random-effects model was adopted. The network meta-analysis (treatment effect comparing to aspirin lone) identified ximelagatran (-0.3044, [-0.8601, 0.2502]), dabigatran (-0.2144, [-0.8666, 0.4525]), rivoroxaban (-0.2179, [-0.5986, 0.1628]) and vorapaxar (- 0.2272, [-0.81, 0.1664]) produced better improvements in MAE incidences whereas vorapaxar (0.3764, [-0.4444, 1.124]), warfarin (0.663, [0.3375, 1.037]), ximelagatran (0.7509, [-0.4164, 2.002]) and apixaban (0.8594, [-0.0049, 1.7]) produced less major bleeding events. The indirect comparisons among drug category (difference in incidence comparing to aspirin lone) showed new oral anticoagulants (-0.1974, [-0.284, -0.111]) and PAR-1 antagonists (-0.1239, [-0.215, -0.033]) to besuperior to warfarin (-0.1004, [-0.166, -0.035]) in the occurrences of MAE whereas PAR-1 antagonists (0.4292, [0.2123, 0.6476]) afforded better outcomes in major bleeding events against warfarin (0.5742, [0.3889, 0.7619]) and new oral anticoagulants (1.169, [0.8667, 1.485]). Conclusion: Based on the study results, we cannot recommend the routine administration of new oral anticoagulant as add-on treatment for patients after ACS. However, for ACS patients comorbid with atrial fibrillation, new oral anticoagulant might be superior to warfarin in both efficacy and safety outcomes.
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BACKGROUND: Dabigatran etexilate, a new oral anticoagulant, was recently approved as an efficacious alternative to warfarin for the prevention of first and recurrent stroke in patients with nonvalvular atrial fibrillation. Limited data are available for dabigatran use in patients with a creatinine clearance rate (CrCL) of 15-30 mL/min. Furthermore, current guidelines do not recommend frequent blood monitoring after dabigatran use. We report herein a patient with severe renal dysfunction who exhibited profound coagulopathy after 2 days of dabigatran use. CASE REPORT: An 87-year-old woman was admitted for altered mental status and left-side weakness. She was diagnosed with right middle cerebral artery infarction. The baseline assessment revealed a serum creatinine concentration of 1.29 mg/dL and a CrCL of 27.2 mL/min. Dabigatran therapy was started 5 weeks after admission at a dosage of 110 mg twice daily. After 2 days of dabigatran use, the patient developed multiple bruises and evidence of upper-gastrointestinal bleeding. Laboratory tests demonstrated a severe coagulopathy, with a prothrombin time of 85.9 sec, an international normalized ratio of 11.36, an activated partial thromboplastin time of 119.2 sec, and a thrombin time of 230.8 sec. Serial assessment of the patient's renal function revealed substantial fluctuation of the CrCL (range, 17.9-26.5 mL/min). CONCLUSIONS: The present case emphasizes the need for frequent checking of renal function and assessment using coagulation assays after commencing dabigatran therapy in patients with moderate-to-severe renal impairment.
Subject(s)
Aged, 80 and over , Female , Humans , Anticoagulants , Atrial Fibrillation , Contusions , Creatinine , Dabigatran , Hemorrhage , Infarction, Middle Cerebral Artery , International Normalized Ratio , Partial Thromboplastin Time , Prothrombin Time , Stroke , Thrombin Time , WarfarinABSTRACT
Only anticoagulation has been shown to reduce atrial fibrillation-related deaths. Vitamin K antagonists are difficult to use due to their narrow therapeutic range, unpredictable response, requirement for frequent coagulation monitoring, frequent dose adjustment, slow onset-offset, and numerous drug-drug and drug-food interactions. New oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, and apixaban have been developed and are available in Korea, and edoxaban was shown to be effective and safe, also. NOACs showed better pharmacodynamics with predictable serum concentrations and effects, and no requirement for coagulation monitoring. These drugs have been shown to be more effective and safer than warfarin for prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Broad, appropriate, and aggressive use of NOACs would improve the results of treatment in patients with nonvalvular atrial fibrillation in Korea.