BACKGROUND The use of apixaban in chronic hemodialysis(HD)patients for non-valvular atrial fibrillation(NVAF)is still controversial regarding benefit of stroke protection vs risk of bleeding.Rotational thromboelastome...BACKGROUND The use of apixaban in chronic hemodialysis(HD)patients for non-valvular atrial fibrillation(NVAF)is still controversial regarding benefit of stroke protection vs risk of bleeding.Rotational thromboelastometry(ROTEM)is a point of care method that evaluates clot formation in whole blood and has been used as an evaluation tool for bleeding risk assessment in non-HD apixaban users.AIM To determine whether bleeding risk can be predicted using ROTEM activated with tissue factor(EXTEM)in HD patients receiving apixaban for NVAF.METHODS Nineteen HD patients with NVAF treated with apixaban for at least 8 days were enrolled.Four dosing regimens were recorded as prescribed by their physician,from 2.5 mg once daily on a non-dialysis day to 5 mg twice daily.Standard coagulation tests,along with ROTEM and apixaban drug levels(using liquid anti-Xa assay)were performed once on a non-dialysis day before and two hours after apixaban morning pill administration.Patients were subsequently monitored for thrombotic/bleeding events and all-cause mortality.RESULTS Over a median follow-up period of 36 months,six patients experienced a bleeding event(group A)and 13 remained free of bleeding(group B).Six deaths were recorded:Three due to major bleeding,one from thrombotic stroke,and two unrelated to coagulopathy.EXTEM clotting time(CT)-post was the only parameter that significantly differed between group A and group B(P=0.013).Each 1-second increase in CT-post was linked to an 8%higher likelihood of a bleeding event(odds ratio=1.08,95%confidence interval:1.0-1.17;P=0.048).A significant progressive increase was observed with the drug’s trough and peak levels(P<0.05)across the four dosing regimens but no significant relationship was found between CT and apixaban dose groups.CONCLUSION Early detection of bleeding risk in HD patients with NVAF on Apixaban maybe be effectively achieved through frequent monitoring using ROTEM EXTEM post CT,thereby helping to reduce associated morbidity.展开更多
BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countrie...BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.展开更多
A rapid, specific, sensitive, and precise reverse-phase HPLC method for the quantitative determination of process related and degradation impurities of Apixaban, an anticoagulant drug is described. The developed RP-HP...A rapid, specific, sensitive, and precise reverse-phase HPLC method for the quantitative determination of process related and degradation impurities of Apixaban, an anticoagulant drug is described. The developed RP-HPLC method was successfully applied to the analysis of both Apixaban drug substance and drug product. The chromatographic separation was achieved on a Sigma-Aldrich’s Ascentis Express®C18 (4.6 mm × 100 mm, 2.7 μ) HPLC column with a runtime of 40 min. Mobile phase-A and mobile phase-B were phosphate buffer and acetonitrile respectively. The column oven temperature was set at 35°C and photodiode array detector was set at 225 nm. Nine process related impurities (Imp-1 to Imp-9) have been detected in test sample of Apixaban by using newly developed RP-HPLC method. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to demonstrate the stability-indicating nature of the developed RP-HPLC method. The developed method was validated as per ICH guideline and found to be specific, precise, sensitive and robust.展开更多
临床正在应用的抗血栓药物面临挑战,Apixaban作为新兴的抗血栓药物,正引起业界及临床研究的广泛关注。刚刚结束的欧洲心脏病学年会(European Society of Cardiology,ESC)上报告了关于急性冠脉综合征(Acute Coro-nary Syndrome,ACS)临床...临床正在应用的抗血栓药物面临挑战,Apixaban作为新兴的抗血栓药物,正引起业界及临床研究的广泛关注。刚刚结束的欧洲心脏病学年会(European Society of Cardiology,ESC)上报告了关于急性冠脉综合征(Acute Coro-nary Syndrome,ACS)临床Ⅱ期研究(APPRAISE-1)数据,包括对apixaban在冠心病患者中应用的调查性研究。AP-PRAISE-1试验显示,在合用阿司匹林和氯吡格雷的基础上,apixaban有减少ACS患者再发心血管事件、脑卒中、死亡的趋势;但与对照组比较,无统计学意义。因此Apixaban表现出来的较高的安全性和疗效引起业界广泛的关注。展开更多
Background Enoxaparin is routinely used for prevention of venous thromboembolism （VTE） after total hip or knee arthroplasty. The purpose of this study was to compare the efficacy and safety of apixaban, a newly oral...Background Enoxaparin is routinely used for prevention of venous thromboembolism （VTE） after total hip or knee arthroplasty. The purpose of this study was to compare the efficacy and safety of apixaban, a newly oral direct inhibitor of factor Xa versus enoxaparin. Methods We performed a meta-analysis of relevant randomized-controlled trials （RCTs） identified in PubMed, Cochrane Library, Embase China Biological Medical Literature database, Countries Journal full-text database, VIP database, and WanFang database. The primary efficacy outcome for our meta-analysis was all VTE and all-cause mortality. The secondary efficacy outcomes included major VTE, non-fatal pulmonary embolism, and mortality. The primary safety outcome was bleeding events, categorized as major, clinically relevant non-major, or minor events. Results Four RCTs, involving 14065 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with apixaban was associated with significantly fewer VTE and all-cause mortality （8346 patients, risk ratio （RR）： 0.63, 95% CI 0.42-0.95） and similar incidence of bleeding events （major bleeding, 11 525 patients, RR 0.76, 95% CI 0.43-1.33; clinically relevant non-major bleeding, 11 525 patients, RR 0.83, 95% CI 0.69-1.01; and minor bleeding, 11 828 patients, RR 0.93, 95% CI 0.79-1.09）. However, our meta-analysis revealed similar effects of apixaban with enoxaparin for thromboprophylaxis with regard to the secondary efficacy outcomes. Conclusions Apixaban was more effective than recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty. But more evidence, especially well designed head-to-head RCTs, is needed to confirm the superior efficacy of apixaban.展开更多
文摘BACKGROUND The use of apixaban in chronic hemodialysis(HD)patients for non-valvular atrial fibrillation(NVAF)is still controversial regarding benefit of stroke protection vs risk of bleeding.Rotational thromboelastometry(ROTEM)is a point of care method that evaluates clot formation in whole blood and has been used as an evaluation tool for bleeding risk assessment in non-HD apixaban users.AIM To determine whether bleeding risk can be predicted using ROTEM activated with tissue factor(EXTEM)in HD patients receiving apixaban for NVAF.METHODS Nineteen HD patients with NVAF treated with apixaban for at least 8 days were enrolled.Four dosing regimens were recorded as prescribed by their physician,from 2.5 mg once daily on a non-dialysis day to 5 mg twice daily.Standard coagulation tests,along with ROTEM and apixaban drug levels(using liquid anti-Xa assay)were performed once on a non-dialysis day before and two hours after apixaban morning pill administration.Patients were subsequently monitored for thrombotic/bleeding events and all-cause mortality.RESULTS Over a median follow-up period of 36 months,six patients experienced a bleeding event(group A)and 13 remained free of bleeding(group B).Six deaths were recorded:Three due to major bleeding,one from thrombotic stroke,and two unrelated to coagulopathy.EXTEM clotting time(CT)-post was the only parameter that significantly differed between group A and group B(P=0.013).Each 1-second increase in CT-post was linked to an 8%higher likelihood of a bleeding event(odds ratio=1.08,95%confidence interval:1.0-1.17;P=0.048).A significant progressive increase was observed with the drug’s trough and peak levels(P<0.05)across the four dosing regimens but no significant relationship was found between CT and apixaban dose groups.CONCLUSION Early detection of bleeding risk in HD patients with NVAF on Apixaban maybe be effectively achieved through frequent monitoring using ROTEM EXTEM post CT,thereby helping to reduce associated morbidity.
文摘BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.
文摘A rapid, specific, sensitive, and precise reverse-phase HPLC method for the quantitative determination of process related and degradation impurities of Apixaban, an anticoagulant drug is described. The developed RP-HPLC method was successfully applied to the analysis of both Apixaban drug substance and drug product. The chromatographic separation was achieved on a Sigma-Aldrich’s Ascentis Express®C18 (4.6 mm × 100 mm, 2.7 μ) HPLC column with a runtime of 40 min. Mobile phase-A and mobile phase-B were phosphate buffer and acetonitrile respectively. The column oven temperature was set at 35°C and photodiode array detector was set at 225 nm. Nine process related impurities (Imp-1 to Imp-9) have been detected in test sample of Apixaban by using newly developed RP-HPLC method. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to demonstrate the stability-indicating nature of the developed RP-HPLC method. The developed method was validated as per ICH guideline and found to be specific, precise, sensitive and robust.
文摘临床正在应用的抗血栓药物面临挑战,Apixaban作为新兴的抗血栓药物,正引起业界及临床研究的广泛关注。刚刚结束的欧洲心脏病学年会(European Society of Cardiology,ESC)上报告了关于急性冠脉综合征(Acute Coro-nary Syndrome,ACS)临床Ⅱ期研究(APPRAISE-1)数据,包括对apixaban在冠心病患者中应用的调查性研究。AP-PRAISE-1试验显示,在合用阿司匹林和氯吡格雷的基础上,apixaban有减少ACS患者再发心血管事件、脑卒中、死亡的趋势;但与对照组比较,无统计学意义。因此Apixaban表现出来的较高的安全性和疗效引起业界广泛的关注。
文摘Background Enoxaparin is routinely used for prevention of venous thromboembolism （VTE） after total hip or knee arthroplasty. The purpose of this study was to compare the efficacy and safety of apixaban, a newly oral direct inhibitor of factor Xa versus enoxaparin. Methods We performed a meta-analysis of relevant randomized-controlled trials （RCTs） identified in PubMed, Cochrane Library, Embase China Biological Medical Literature database, Countries Journal full-text database, VIP database, and WanFang database. The primary efficacy outcome for our meta-analysis was all VTE and all-cause mortality. The secondary efficacy outcomes included major VTE, non-fatal pulmonary embolism, and mortality. The primary safety outcome was bleeding events, categorized as major, clinically relevant non-major, or minor events. Results Four RCTs, involving 14065 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with apixaban was associated with significantly fewer VTE and all-cause mortality （8346 patients, risk ratio （RR）： 0.63, 95% CI 0.42-0.95） and similar incidence of bleeding events （major bleeding, 11 525 patients, RR 0.76, 95% CI 0.43-1.33; clinically relevant non-major bleeding, 11 525 patients, RR 0.83, 95% CI 0.69-1.01; and minor bleeding, 11 828 patients, RR 0.93, 95% CI 0.79-1.09）. However, our meta-analysis revealed similar effects of apixaban with enoxaparin for thromboprophylaxis with regard to the secondary efficacy outcomes. Conclusions Apixaban was more effective than recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty. But more evidence, especially well designed head-to-head RCTs, is needed to confirm the superior efficacy of apixaban.
