阿哌沙班、利伐沙班、达比加群酯、依诺肝素预防髋膝关节置换术后静脉血栓形成的成本-效果分析

目的：评价阿哌沙班、利伐沙班、达比加群酯、依诺肝素预防髋膝关节置换术后静脉血栓栓塞症的成本-效果比,为临床药物选择提供经济学参考。方法：建立髋膝关节置换术后预防静脉血栓栓塞症的决策树模型,参考Meta分析研究结果确定模型中各节点概率,运行数据模型TreeAge Pro 2011得出成本-效果比。结果：全髋关节置换术中阿哌沙班预防用药成本-效果比3 950.43;利伐沙班预防用药成本-效果比2 900.08;达比加群酯成本-效果比3 149.79;依诺肝素成本-效果比3 763.86,全膝关节置换术中阿哌沙班预防用药成本-效果比1 594.70;利伐沙班预防用药成本-效果比1 169.91;达比加群酯成本-效果比1 266.61;依诺肝素成本-效果比1 524.10。结论：利伐沙班预防髋膝关节置换术术后静脉血栓形成相比阿哌沙班、达比加群酯、依诺肝素更具有经济优势。在预防全膝关节置换术中,依诺肝素相比阿哌沙班、利伐沙班、达比加群酯预防用药增加的成本可被接受。     

利伐沙班与低分子肝素预防髋膝关节置换术后静脉血栓栓塞的成本-效果对比观察

目的:分析髋膝关节置换术后静脉血栓栓塞症(venous thrombus embolism,VTE)应用利伐沙班与低分子肝素预防的成本-效果.方法:选取2019年1月—2019年12月在我院接受髋膝关节置换术治疗的128例患者临床资料,按治疗方案不同分2组,各组64例,对照组采用依诺肝素预防治疗,观察组采用利伐沙班预防...     

利伐沙班预防髋或膝关节置换术后静脉血栓栓塞症的Meta分析

通过Meta分析评价Xa因子抑制剂利伐沙班与低分子肝素依诺肝素比较对择期髋或膝置换术后VTE发生率的影响。方法　计算机检索数据库MEDLINE（1966年至2010年3月）、PubMed（1966年至2010年3月）、EMBASE（1966年至2010年3月）、Cochrane图书馆（2010年第3期）、中国生物医学文献数据库（1978年至2010年3月）、中国期刊全文数据库（1980年至2010年3月）、中国科技期刊数据库（1989年至2010年3月）中关于利伐沙班与依诺肝素比较预防择期髋或膝置换术后VTE发生的临床随机对照研究,并查阅所有检出文献和相关综述的参考文献作为补充文献,截止到2010年3月。采用RevMan 5.0软件进行统计分析,利伐沙班组与依诺肝素组总静脉血栓栓塞症、重大静脉血栓栓塞症、出血事件和心血管不良事件发生率采用优势比评价。结果　共纳入前瞻性随机对照研究4篇。Meta分析结果显示,与依诺肝素组比较利伐沙班能够降低择期髋或膝置换患者总静脉血栓栓塞症发生率（优势比0.38,95%置信区间[0.23,0.61],P<0.001）和重大静脉血栓栓塞症发生率（优势比0.25,95%置信区间[0.11,0.56],P<0.001）,而出血事件和心血管不良事件发生率差异无统计学意义。结论 口服利伐沙班能够减少择期髋或膝置换术后VTE的发生率,不增加出血事件及心血管不良事件的发生风险。     

利伐沙班和磺达肝癸钠在髋、膝关节置换术后预防静脉血栓有效性和安全性的meta分析

目的比较利伐沙班和磺达肝癸钠在髋、膝关节置换术后预防静脉血栓的有效性和安全性,为临床用药提供参考数据。方法通过收集利伐沙班、磺达肝癸钠与依诺肝素预防静脉血栓的随机双盲对照试验进行meta分析,采用ITC程序间接比较利伐沙班与磺达肝癸钠的有效性和安全性。结果共纳入研究文献11篇,病例总数20 217例;与依诺肝素相比,利伐沙班能降低近端DVT[RR=0.21,95%CI(0.14,0.32)]和症状性VTE[RR=0.67,95%CI(0.33,0.69)]发生的风险,差异有统计学意义;磺达肝癸钠预防近端DVT和症状性VTE效果与依诺肝素相比,差异无统计学意义(P=0.06),但能增加大出血事件[RR=1.60,95%CI(1.16,2.20)]发生风险,其差异有统计学意义;间接比较显示利伐沙班疗程<15 d疗效和安全性与磺达肝癸钠差异无统计学意义;与磺达肝癸钠相比,当利伐沙班疗程>15 d,能更有效预防近端DVT[RR=0.18,95%CI(0.05,0.61)]和症状性VTE[RR=0.22,95%CI(0.06,0.86)],在大出血事件的风险上差异无统计学意义[RR=1.47,95%CI(0.37,5.88)]。结论利伐沙班与磺达肝癸钠疗程相近时,两者疗效和安全性比较差异无统计学意义;适当延长利伐沙班疗程可能会更好地预防静脉血栓栓塞。     

利伐沙班与低分子肝素预防人工全膝关节置换术后深静脉血栓形成的效果

目的：观察利伐沙班和低分子肝素对于人工全膝关节置换术后深静脉血栓的预防效果。方法：2014年4月～2015年4月,80例患者在我院行人工全膝关节置换术。依据术后治疗方法将其分为观察组与对照组,每组40例。对照组术后应用低分子肝素,观察组应用利伐沙班。对比分析两组术后深静脉血栓的发生率和满意度。结果：观察组术后深静脉血栓的发生率为10.0%,满意度为92.5%,对照组术后深静脉血栓的发生率为22.5%,满意度为80.0%,差异有统计学意义（P<0.05）。结论：在人工全膝关节置换术后对患者使用利伐沙班,可以有效地预防深静脉血栓,提高预后质量和满意度。     

利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症疗效与安全性比较的Meta分析

目的:比较利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症的疗效与安全性,为临床用药提供循证参考.方法:计算机检索PubMed、Embase、Cochrane图书馆、Clinical Trials、中国期刊全文数据库、中国生物医学文献数据库、维普网等数据库,收集利伐沙班对比依诺肝素的临床试验或观察性研究,检索时限均为各...     

利伐沙班与低分子肝素预防人工全髋关节置换术后深静脉血栓效果比较

目的观察利伐沙班与低分子肝素在预防人工全髋关节置换深静脉血栓的疗效和安全性。方法 2009年02月—2011年05月行人工全髋关节置换术的患者200例分为两组:利伐沙班组100例,术前6⁸ h给予利伐沙班10 mg口服,1次/d,连续14 d;低分子肝素组100例,术后给予低分子肝素5000 U,1次/d皮下注射,连续14 d。术后14 d行双下肢静脉彩超检查有无深静脉血栓形成,并观察两组用药期间有无肺动脉栓塞和严重出血事件的发生。结果利伐沙班组深静脉血栓形成的发生率6%,显著低于低分子肝素组10%(P<0.05),两组均未发生肺动脉栓塞和严重出血事件。结论利伐沙班较低分子肝素能更有效预防髋关节置换术后下肢深静脉血栓的形成。二者均较安全。     

利伐沙班用于预防髋关节置换术后下肢深静脉栓塞的临床观察

目的观察利伐沙班对髋关节置换术后下肢深静脉栓塞(DVT)的预防效果。方法将83例行髋关节置换术后患者随机分为A、B两组,A组42例,B组41例。A组应用利伐沙班口服,实用时间为14d;B组应用低分子肝素(LMWH),使用时间为14d。比较两组的疗效结果。两组在治疗期间均无严重出血。结果 A组出现DVT 2例(4.76%),B组出现DVT 2例(4.87%),A组DVT发生率与B组相当,差异无统计学意义(P>0.05)。结论利伐沙班用于预防髋关节置换术后下肢深静脉栓塞效果良好。利伐沙班在预防全髋置换后下肢深静脉血栓的疗效与安全性上与低分子肝素作用相当。     

髋、膝关节置换术后应用利伐沙班预防深静脉血栓的疗效观察

目的观察应用利伐沙班预防髋、膝关节置换术后深静脉血栓的临床疗效及安全性。方法以2010年10月~2012年3月我院收治的需行髋、膝关节置换术并符合入选标准的176例患者为研究对象,按就诊顺序随机分为治疗组(利伐沙班组)和对照组(低分子肝素组),每组各88例。在相同常规治疗的基础上,分别口服利伐沙班(1日10mg)和皮下注射低分子肝素(1日100Axa IC.U.kg-1)进行深静脉血栓的预防,观察比较两组的治疗效果及安全性。结果利伐沙班组和低分子肝素组深静脉血栓的发生率分别为8.0%和18.2%,两者相比具有统计学差异(P<0.05),安全性方面利伐沙班与低分子肝素相近(P>0.05),两组均无严重大出血事件发生。结论利伐沙班用于预防髋、膝关节置换术后深静脉血栓的发生疗效可靠,安全性与低分子肝素相当,口服治疗更方便,值得临床推广应用。     

利伐沙班预防髋关节置换术后深静脉血栓疗效观察

目的观察利伐沙班预防髋关节置换术后深静脉血栓临床疗效。方法选取2011年4月-2013年10月医院行髋关节置换术患者53例（56髋）,随机分为利伐沙班27例（29髋）和低分子肝素组26例（27髋）。利伐沙班组术后每天予利伐沙班片10mg口服,持续2周;低分子肝素组每天予低分子肝素钠4100IU皮下注射,持续2周;治疗2周后使用彩色多普勒超声检查2组患者静脉血栓形成状况,同时检测手术前后APTT、PT、PLT的各项指标并记录手术后的引流量。结果利伐沙班组的患者发生静脉血栓1例（3.7%）,明显低于低分子肝素组的4例（15.4%）,2组比较差异有统计学意义（P〈0.05）;2组患者术后引流量比较差异无统计学意义（P＆gt;0.05）;2组患者手术后14d的APTT、PT、PLT值比较差异无统计学意义（P＆gt;0.05）。2组均无肺动脉栓塞事件或严重出血事件发生。结论利伐沙班预防髋关节置换术后深静脉血栓效果肯定,值得临床推广应用。     

Rivaroxaban

Rivaroxaban (Xarelto?), an oral oxazolidinone-based anticoagulant, is a potent, selective, direct inhibitor of factor Xa that is used in the prevention of venous thromboembolism (VTE) in adult patients after total hip replacement (THR) or total knee replacement (TKR) surgery. In large, clinical trials, oral rivaroxaban 10?mg once daily was more effective than subcutaneous enoxaparin 40?mg once daily in preventing postoperative VTE in patients undergoing THR or TKR surgery. Rivaroxaban was associated with significantly lower incidences of the primary endpoint, total VTE (composite of deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause) compared with enoxaparin regimens across all studies. For example, in the largest trial in patients undergoing THR, total VTE occurred in 1.1% of rivaroxaban recipients and 3.7% of enoxaparin recipients (absolute risk reduction 2.6% [95% CI 1.5, 3.7]) in the modified intent-to-treat population. Notably, the greater efficacy of rivaroxaban was achieved without a significant increase in the incidence of major bleeding episodes compared with enoxaparin; bleeding events were the most frequently reported adverse events across clinical trials. Pyrexia, vomiting, nausea, and constipation were the most frequently reported of the non-bleeding treatment-emergent adverse events in rivaroxaban recipients and occurred at a similar rate to that with enoxaparin treatment. In addition, preliminary pharmacoeconomic analyses in Canada and the US indicate that rivaroxaban is a cost-saving treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective option for the prophylaxis of VTE following THR and TKR.     

Drug evaluation: rivaroxaban, an oral, direct inhibitor of activated factor X

Bayer AG and Ortho-McNeil Pharmaceutical Inc are developing rivaroxaban, an oral Factor Xa inhibitor, for the potential prevention and treatment of thrombosis. In December 2005 and December 2006, phase III trials were initiated for the prevention of venous thromboembolism (VTE) following major orthopedic surgery and in patients with atrial fibrillation, respectively. By January 2007, a phase III trial for the prevention of VTE following total knee replacement surgery had commenced. In November 2006, a phase II trial for the reduction of VTE in patients with acute coronary syndrome was initiated.     

Cost/death averted with venous thromboembolism prophylaxis in patients undergoing total knee replacement or knee arthroplasty

STUDY OBJECTIVE: To compare the cost-effectiveness of warfarin or enoxaparin with no prophylaxis for prevention of venous thromboembolism in patients undergoing total knee replacement (TKR) or knee arthroplasty. DESIGN: Literature search and retrospective database analysis. PATIENTS: Cohort of 42,692 patients over 40 years old who underwent TKR or knee arthroplasty, with a subsequent length of stay of at least 1 day, and who did not die postoperatively. MEASUREMENTS AND MAIN RESULTS: Both warfarin and enoxaparin were superior to no prophylaxis with regard to costs and clinical outcomes. Enoxaparin was associated with medical charges of $26,455/patient and prevented 194 deaths/10,000 patients. Warfarin was associated with medical charges of $27,360/patient and prevented 124 deaths/10,000 patients. CONCLUSIONS: A wide range of model estimates and assumptions identify enoxaparin as the prophylaxis modality of choice for preventing venous thromboembolism and subsequent clinical complications following total knee replacement surgery.     

Apixaban: a review of its use in the prevention of venous thromboembolism after knee or hip replacement surgery

Apixaban (Eliquis?) is an orally active and selective direct inhibitor of factor Xa indicated for twice-daily use in the EU for the prevention of venous thromboembolism (VTE) in adults who have had knee or hip replacement surgery. In this article, the pharmacological, clinical efficacy and tolerability data relevant to the use of apixaban in this indication are reviewed. Oral apixaban is a generally effective and well tolerated thromboprophylactic agent for use after major orthopaedic surgery. In the large, randomized, double-blind, phase III, noninferiority trials known as ADVANCE-2 and -3, apixaban 2.5?mg twice daily initiated after surgery was generally more effective in preventing VTE in patients undergoing knee or hip replacement surgery than subcutaneous enoxaparin sodium initiated before surgery at the EU recommended dosage of 40?mg once daily, with apixaban conferring this benefit without significantly increasing the risk of bleeding. However, when the same apixaban regimen was compared with the US recommended dosage regimen of subcutaneous enoxaparin sodium (30?mg twice daily, initiated after surgery) in patients undergoing knee replacement surgery in the similarly designed ADVANCE-1 trial, the thromboprophylactic efficacy of apixaban did not meet primary endpoint noninferiority criteria, although apixaban was associated with fewer major or clinically relevant nonmajor bleeds (composite endpoint) than this enoxaparin sodium regimen. Additional comparative efficacy and tolerability data are required to definitively position apixaban with respect to other anticoagulants, including rivaroxaban and dabigatran etexilate. In the meantime, currently available clinical data indicate that apixaban is an emerging option for the prevention of VTE in patients undergoing knee or hip replacement surgery.     

New oral anticoagulants for venous thromboembolism: focus on factor Xa and thrombin inhibitors

Several oral direct anti-Xa agents and one antithrombin agent are currently under clinical development for the prevention and treatment of venous thromboembolism (VTE). The anti-Xa inhibitors rivaroxaban (10 mg once daily) and apixaban (2.5 mg twice daily) as well as the thrombin inhibitor dabigatran (150 or 220 mg once daily) have been recently licensed for the prevention of VTE in total hip or knee replacement. The publication of the results of studies with rivaroxaban and apixaban in the prevention of VTE in medical patients are awaited. Phase III studies on the treatment of VTE showed the non inferiority of rivaroxaban (15 mg twice daily in the first three weeks and 20 mg once daily thereafter) and dabigatran (150 mg twice daily) to standard treatment. The incidence of major or clinically relevant non-major bleeding was similar in patients receiving standard treatment and rivaroxaban or dabigatran. Clinical trials on VTE treatment are currently ongoing with apixaban and edoxaban. A number of phase II clinical trials are currently ongoing with several other antiXa agents in the prophylaxis and treatment of VTE.     

Dabigatran etexilate

Dabigatran etexilate is an orally administered prodrug of dabigatran, which is a potent, concentration-dependent inhibitor of thrombus formation and thrombin-induced platelet aggregation. Dabigatran etexilate pharmacokinetics were linear across a wide dosage range. There were no clinically important pharmacokinetic interactions with digoxin (a P-glycoprotein substrate), pantoprazole (a proton-pump inhibitor) or drugs that are substrates and/or inhibitors of hepatic cytochrome P450 enzymes. In two large, randomized, double-blind trials of the prevention of venous thromboembolism (VTE) in patients undergoing total hip or total knee replacement surgery, orally administered dabigatran etexilate 220 mg/day was noninferior to subcutaneous enoxaparin sodium 40 mg/day for the primary composite endpoint of total VTE events or all-cause mortality during the treatment period. There were no significant differences between dabigatran etexilate and enoxaparin sodium in major VTE events and VTE-related mortality. Across trials, < or =0.5% of patients experienced a symptomatic pulmonary embolus or died. Dabigatran etexilate was generally well tolerated. In patients undergoing total hip or total knee replacement surgery, there was no significant difference between dabigatran etexilate and enoxaparin sodium recipients in the incidence of major or minor bleeding.     

Ximelagatran/Melagatran: a review of its use in the prevention of venous thromboembolism in orthopaedic surgery

Ximelagatran (Exanta), the first available oral direct thrombin inhibitor, and its active form, melagatran, have been evaluated in the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement.After oral administration ximelagatran is rapidly bioconverted to melagatran. Melagatran inactivates both circulating and clot-bound thrombin by binding to the thrombin active site, thus, inhibiting platelet activation and/or aggregation and reducing fibrinolysis time.The efficacy of subcutaneous melagatran followed by oral ximelagatran has been investigated in four European trials and the efficacy of an all oral ximelagatran regimen has been investigated in five US trials. In a dose-ranging European study, preoperatively initiated subcutaneous melagatran 3 mg twice daily followed by oral ximelagatran 24 mg twice daily was significantly more effective than subcutaneous dalteparin sodium 5000IU once daily in preventing the occurrence of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing hip or knee replacement. In one study, there were no significant differences in VTE prevention between subcutaneous melagatran 3 mg administered after surgery followed by ximelagatran 24 mg twice daily and enoxaparin sodium (enoxaparin) 40 mg once daily. Compared with enoxaparin, significantly lower rates of proximal DVT and/or PE (major VTE) and total VTE were observed when melagatran was initiated preoperatively (2mg) then postoperatively (3mg) and followed by ximelagatran 24 mg twice daily. In the US, four studies showed that postoperatively initiated ximelagatran 24 mg twice daily was of similar efficacy to enoxaparin or warfarin in the prevention of VTE in patients undergoing hip or knee replacement. However, ximelagatran 36 mg twice daily was superior to warfarin (target international normalised ratio of 2.5) at preventing the incidence of VTE in patients undergoing total knee replacement in two studies.Ximelagatran alone or after melagatran was generally well tolerated. Overall, the incidence of bleeding events and transfusion rates were not markedly different from those documented for comparator anticoagulants. In a post-hoc analysis of one study, transfusion rates were lower in ximelagatran than enoxaparin recipients.CONCLUSIONS: Oral ximelagatran alone or in conjunction with subcutaneous melagatran has shown good efficacy and was generally well tolerated in the prevention of VTE in patients undergoing orthopaedic surgery. Furthermore, patients receiving ximelagatran/melagatran do not require anticoagulant monitoring. The drug has a low potential for drug interactions and can be administered either by subcutaneous injection or orally. Thus, on the basis of available evidence, ximelagatran/melagatran appears poised to play an important role in the prophylaxis of VTE in patients undergoing orthopaedic surgery.