More light at the end of the tunnel – apixaban in atrial fibrillation

Introduction: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation.

Areas covered: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups.

Expert opinion: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.     

阿哌沙班预防心房颤动患者的卒中

阿哌沙班是激活Ⅹ因子(Ⅹa)抑制剂,具有快速吸收、线性药代动力学、较少药物相互作用的特点。在不适合接受华法林治疗的心房颤动人群中所进行的随机对照试验证实,阿哌沙班在减少卒中和系统栓塞方面的疗效优于阿司匹林,安全性相似;在至少有1个危险因素的心房颤动人群中进行的与华法林的对照试验中,阿哌沙班可减少卒中和栓塞事件,主要是减少出血性卒中,同时减少重要出血和全因死亡。     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

Apixaban: a new player in the anticoagulant class

Apixaban (BMS-562247-01) is a compound being investigated as an anticoagulant. Apixaban molecule is developed in a joint venture by Pfizer and Bristol-Myers Squibb. Apixaban, a coagulation factor Xa inhibitor, approved in the E.U. in 2011 for the prevention of venous thromboembolic events in adult patients, who have undergone elective hip or knee replacement. The Apixaban based drug will be marketed under the brand name Eliquis? and is expected to rack up annual sales of over $2.5 billion. Apixaban is expected to provide stiff competition to warfarin, a popular blood thinner used in Europe. Warfarin is known to cause some serious side effects in patients. Apixaban, as compared with aspirin, reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrillation by more than 50% (from 3.7% per annum with aspirin to 1.6% per annum with apixaban). Apixaban exhibits superiority to enoxaparin in preventing thrombosis in patients undergoing elective hip replacement surgery with similar bleeding rates. Apixaban is a highly selective and potent Factor Xa Inhibitor with Ki=0 8nM to both free as well as prothrombinase bound FXa. In X-ray crystal structure studies indicate that the pyrazole N-2 nitrogen atom interacts with backbone of Gln192 and the carbonyl oxygen of carboxamide interacts with NH of Gly216. The orientation of phenyllactum in the S4 region indiacates an edge to face interaction with Trp215, which is positioned between the Tyr99 and Phe174. In the present review, we have tried to cover comparative study of various FXa-inhibitors and point out apixaban in the various aspect including molecular chemistry, physical properties, commercial synthesis, current patent status, crystalline polymorphic forms, molecular receptor interaction, pharmacophore rational, mechanism of action, clinical studies, preclinical, adverse effect, available formulation, dose regimen and co-therapy, thus giving emphasis on medicinal chemistry aspects.     

Novel oral anticoagulants: clinical pharmacology, indications and practical considerations

Background

Novel oral anticoagulants are approved in several indications: rivaroxaban, apixaban, and dabigatran for the prevention of venous thromboembolism after elective hip or knee replacement surgery, and edoxaban for hip or knee replacement surgery and hip fracture surgery (in Japan only); rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE; and rivaroxaban, apixaban, and dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. These agents overcome some limitations of traditional anticoagulants, are suggested to have no requirement for routine coagulation monitoring, and are administered orally. Rivaroxaban, apixaban, and dabigatran have different pharmacological characteristics, and guidance is needed on optimum doses and dosing intervals and the effects of renal or hepatic impairment, age, food, and other drugs. Dabigatran has stricter prescribing advice than rivaroxaban or apixaban for patients with moderate-to-severe renal impairment. All three drugs have restrictions on use in patients with hepatic impairment. Apixaban requires twice-daily dosing in all indications, whereas rivaroxaban and dabigatran are dosed once- or twice-daily depending on indication. Although head-to-head comparisons are lacking, the novel oral anticoagulants may show favorable cost–benefit relations compared with traditional vitamin K antagonists or no therapy.

Aim

This review summarizes the pharmacology of rivaroxaban, apixaban, edoxaban, and dabigatran, and the indications for which they are approved. Issues regarding the optimization of the use of these anticoagulants for the management of thromboembolic disorders will also be discussed.     

新型口服抗凝药物的安全性

新型抗凝药物主要包括直接凝血酶抑制剂和Xa因子抑制剂。其中,直接凝血酶抑制剂达比加群酯口服制剂、直接Xa因子抑制剂利伐沙班和阿哌沙班口服制剂已在我国上市;另外一种直接Xa因子抑制剂贝曲沙班口服制剂也正在进行Ⅲ期临床研究;而直接Xa因子抑制剂爱多沙班口服制剂已在日本上市。达比加群酯致颅内出血发生风险低于华法林,但该药可能增加急性冠状动脉综合征患者严重出血和具有临床意义轻度出血的发生率,以及心肌梗死或急性冠状动脉综合征的发生风险。利伐沙班在预防非瓣膜性心房颤动所致脑卒中和栓塞方面优于华法林,预防骨科术后血栓效果优于依诺肝素,大出血事件发生风险与两药相似,而颅内出血发生风险低于华法林。阿哌沙班在降低心房颤动患者脑卒中或全身性栓塞发生率及病死率方面优于华法林,颅内出血发生率低于华法林,大出血发生率与华法林相似或降低;阿哌沙班的安全性与用药剂量相关。爱多沙班的主要不良反应为出血,用于心房颤动患者的有效性及安全性均优于华法林。贝曲沙班用于全膝关节置换术后预防血栓效果与依诺肝素相似,出血发生率低于依诺肝素。     

Role of Emerging Antithrombotic Therapy in the Prevention of Cardioembolic Complications in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS₂ or CHA₂DS₂-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p=0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p<0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in ～18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in ～20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.     

Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke

ABSTRACT

Introduction: In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60–70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs).

Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications.

Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF.     

Indobufen: an updated review of its use in the management of atherothrombosis

Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme thereby suppressing thromboxane synthesis. Clinical trials have evaluated the efficacy of oral indobufen in the secondary prevention of thromboembolic complications in patients with or without atrial fibrillation, in the prevention of graft occlusion after coronary artery bypass graft (CABG) surgery and in the treatment of intermittent claudication. In the secondary prevention of thromboembolic events indobufen 200 mg once or twice daily was significantly more effective than no treatment although not as effective as ticlopidine 250 mg once or twice daily, during 1-year nonblind clinical trials. Compared with placebo, indobufen 100 mg twice daily significantly reduced the risk of stroke in a small 28-month trial of patients at increased risk of systemic embolism (50% had atrial fibrillation). Furthermore, in patients with nonrheumatic atrial fibrillation and a recent cerebrovascular event enrolled in the 1-year Studio Italiano Fibrillazione Atriale (SIFA) trial, indobufen 100 or 200 mg twice daily was as effective as warfarin (titrated to produce an international normalised ratio of 2.0 to 3.5) in the secondary prevention of thromboembolic events; the incidences of the composite end-point of major vascular events (10.6 vs 9.0%) and recurrent stroke (5 vs 4%) were similar between treatments. In 2 large 12-month trials, the Studio Indobufene nel Bypass Aortocoronarico (SINBA) and the UK study, indobufen 200 mg twice daily was as effective as aspirin (acetylsalicylic acid) 300 or 325 mg plus dipyridamole 75 mg 3 times daily in the prevention of early and late occlusion of saphenous grafts in patients after CABG surgery. Indobufen 200 mg twice daily for 6 months significantly improved walking capacity compared with placebo, and caused a more pronounced improvement in both pain-free and total walking distance than either pentoxifylline 300 mg or aspirin 500 mg twice daily in separate 6- and 12-month studies of patients with intermittent claudication. Oral indobufen up to 200 mg twice daily was generally well tolerated in >5000 patients with atherosclerotic disease. Adverse events (predominantly gastrointestinal), reported by 3.9% of patients, rarely required withdrawal from treatment. In the SINBA and UK studies, fewer adverse events and less gastrointestinal bleeding were seen with indobufen than with aspirin plus dipyridamole treatment, while in the SIFA trial, noncerebral bleeding events occurred significantly less frequently in indobufen than warfarin recipients (0.6 vs 5.1%) and major bleeding events occurred only in the warfarin group. Conclusion: Indobufen is as effective as warfarin in the prophylaxis of thromboembolic events in at risk patients with nonrheumatic atrial fibrillation, as aspirin plus dipyridamole in the prevention of CABG occlusion and may be more effective than aspirin or pentoxifylline in improving walking capacity in patients with intermittent claudication. The improved tolerability profile of indobufen (favourable gastric tolerance and reduced haemorrhagic complications) compared with aspirin 300 to 325 mg 3 times daily or warfarin, in addition to a similar antiplatelet effect, suggests indobufen can be considered a drug with a definite role in the management of atherothrombotic events. In particular, indobufen may be an effective alternative for at risk patients with nonrheumatic atrial fibrillation in whom anticoagulant therapy is contraindicated or who are at higher risk of bleeding.     

Ximelagatran

Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using ximelagatran across the population at risk, reducing the incidence of thromboembolic events.     

Spotlight on dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation

The need for safe, effective and easily administered and monitored antithrombotic treatments that do not have the issues common to warfarin treatment has led to the development of new anticoagulant drugs. Dabigatran etexilate (Pradaxa?, Pradax?) is a prodrug of the direct thrombin inhibitor dabigatran, a direct, reversible, potent inhibitor of thrombin. Dabigatran does not interact with food, and is associated with very few known drug interactions. Dabigatran etexilate, at dosages of 110 and 150 mg twice daily, was shown to be noninferior to warfarin with regard to the incidence of stroke or systemic embolism in a large, randomized, partially blinded, multicentre study in a wide spectrum of patients with atrial fibrillation. Moreover, the higher dosage was associated with significantly greater efficacy than warfarin in this regard. These results were supported by secondary endpoints and subgroup analyses. In general, dabigatran etexilate is well tolerated, although it is associated with a higher rate of dyspepsia than warfarin. Major bleeding was as common in recipients of the higher dosage as, and less common in recipients of the lower dosage of dabigatran etexilate than, that in recipients of warfarin, and intracranial bleeding, life-threatening major bleeding and total bleeding were less common in recipients of either dabigatran etexilate dosage than in warfarin recipients. However, the higher dosage of dabigatran etexilate was associated with a higher rate of gastrointestinal bleeding than warfarin was. The incidence of hepatotoxicity did not significantly differ across treatment groups. In conclusion, dabigatran etexilate 150 mg twice daily is more effective than warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation, and is generally well tolerated, particularly with regard to bleeding endpoints compared with warfarin. It requires more frequent administration than warfarin, but provides multiple improvements to various issues associated with warfarin administration. Direct comparisons with other new anticoagulant drugs would be beneficial, as would further investigation into the effects in different patient populations, long-term effects, and the gastrointestinal bleeding and dyspepsia observed with dabigatran etexilate treatment. Dabigatran etexilate is a promising new option for the prevention of stroke and systemic embolism in patients with atrial fibrillation.     

Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.     

吲哚布芬用于心房颤动的网状Meta及药物经济学评价

目的：评估吲哚布芬与抗凝药物用于非瓣膜性心房颤动患者的有效性、安全性及经济性。方法：系统检索吲哚布芬与抗凝药物治疗非瓣膜性心房颤的临床试验。采用网状Meta分析评价吲哚布芬与抗凝药物的疗效及安全性。从支付方角度,以成本-效果分析进行药物经济性评价。结果：本研究共纳入5篇研究,房颤患者72 599例。吲哚布芬与阿哌沙班（RR：0.97,95% CI：0.92,1.03）、达比加群酯110 mg（RR：1.03,95% CI：0.98;1.09）在临床净效益（卒中、系统性栓塞、出血事件及全因死亡率）事件发生数上无统计学差异。吲哚布芬与利伐沙班（RR：1.167,95% CI：1.10;1.23）、达比加群酯150 mg（RR：1.10,95% CI：1.04;1.16）、依度沙班（RR：1.07,95% CI：1.02;1.14）、华法林（RR：1.22,95% CI：1.15;1.29）相比,吲哚布芬可降低临床净效益事件发生数。原始研究中,在一年观察期内吲哚布芬组未观察到任何严重出血事件发生。吲哚布芬日成本27.8元,低于抗凝药物。结论：吲哚布芬可降低临床净效益事件发生数,降低临床相关非严重出血事件的发生率,在观察期内未出现严重出血事件。此外,吲哚布芬的日均成本低于抗凝药物,具有一定的成本优势。由于缺乏直接比较结果,未来仍需进一步开展多中心大样本的临床试验,为判断吲哚布芬治疗房颤疗效、安全性及经济性提供证据支持。     

Dietary implications for patients receiving long-term oral anticoagulation therapy for treatment and prevention of thromboembolic disease

Introduction: The effectiveness of oral anticoagulation therapy with warfarin (a vitamin K antagonist) in the treatment of thromboembolic disease, including stroke prophylaxis in patients with atrial fibrillation is well recognised. However, warfarin has a narrow therapeutic window and an unpredictable anticoagulation response, which make it difficult to achieve and maintain optimal anticoagulation. Various dietary factors, including sudden changes in eating patterns, can significantly alter anticoagulation control, thereby potentially exposing patients to the risk of bleeding or thromboembolic complications. Dietary vitamin K intake is a particularly important factor, given the mechanism of action of warfarin.

Areas covered: In this article, we cover the sources of vitamin K and their potential effect of dietary vitamin K on anticoagulation response to warfarin. We also discuss the results of studies on the effect of vitamin K supplementation on anticoagulation stability.

Expert commentary: A stable dietary vitamin K, promoted by daily oral vitamin K supplementation, can improve anticoagulation stability in patients on warfarin therapy. There is experimental evidence in animals that dietary vitamin K affects anticoagulation response to the direct thrombin inhibitor, ximelagatran. Whether dietary vitamin K affects anticoagulation response to the currently licensed direct oral anticoagulants (DOACs) in man remains to be investigated.     

Direct oral anticoagulants and cardiovascular prevention in patients with nonvalvular atrial fibrillation

Introduction: Patients with atrial fibrillation have an increased risk for stroke, systemic embolism and cardiovascular events, including myocardial infarction and cardiovascular death. However, the majority of studies that have analyzed the efficacy of anticoagulants have been focused only on their effects on the risk of stroke.

Areas covered: The available evidence about the association between atrial fibrillation and cardiovascular disease as well as the effects of oral anticoagulation on cardiovascular death and myocardial infarction, with a particular focus on direct oral anticoagulants, was updated in this review.

Expert opinion: The management of patients with atrial fibrillation should not be limited to the prevention of stroke, but should also include the prevention of cardiovascular events. Despite treatment with vitamin K antagonists, many patients with atrial fibrillation still develop cardiovascular complications, particularly individuals whose anticoagulation is difficult to control. Direct oral anticoagulants overcome the majority of limitations of vitamin K antagonists and compared with warfarin, they lead to a greater reduction in the risk of stroke or systemic embolism, all-cause mortality, and intracranial hemorrhage. Although these drugs can only be compared indirectly, it seems that not all direct oral anticoagulants are equal with regard to the prevention of myocardial infarction.     

Dabigatran Etexilate

The need for safe, effective, and easily administered and monitored antithrombotic treatments that do not have the issues common to warfarin treatment has led to the development of new anticoagulant drugs. Dabigatran etexilate (Pradaxa®, Pradax?) is a prodrug of the direct thrombin inhibitor dabigatran, a direct, reversible, potent inhibitor of thrombin. Dabigatran does not interact with food, and is associated with very few known drug interactions. Dabigatran etexilate, at dosages of 110 and 150 mg twice daily, was shown to be noninferior to warfarin with regard to the incidence of stroke or systemic embolism in a large, randomized, partially blinded, multicenter study in a wide spectrum of patients with atrial fibrillation. Moreover, the higher dosage was associated with significantly greater efficacy than warfarin in this regard. These results were supported by secondary endpoints and subgroup analyses. In general, dabigatran etexilate is well tolerated, although it is associated with a higher rate of dyspepsia than warfarin. Major bleeding was as common in recipients of the higher dosage as, and less common in recipients of the lower dosage of dabigatran etexilate than, that in recipients of warfarin, and intracranial bleeding, life-threatening major bleeding, and total bleeding were less common in recipients of either dabigatran etexilate dosage than in warfarin recipients. However, the higher dosage of dabigatran etexilate was associated with a higher rate of gastrointestinal bleeding than warfarin. The incidence of hepatotoxicity did not significantly differ across treatment groups. In conclusion, dabigatran etexilate 150 mg twice daily is more effective than warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation, and generally well tolerated, particularly with regard to bleeding endpoints compared with warfarin. It requires more frequent administration than warfarin, but provides multiple improvements to various issues associated with warfarin administration. Direct comparisons with other new anticoagulant drugs would be beneficial, as would further investigation into the effects in different patient populations, long-term effects, and the gastrointestinal bleeding and dyspepsia observed with dabigatran etexilate treatment. Dabigatran etexilate is a promising new option for the prevention of stroke and systemic embolism in patients with atrial fibrillation.     

心房颤动抗栓药物治疗进展

心房颤动(房颤)是导致卒中和外周栓塞的重要独立预测因素,华法林抗凝治疗可降低卒中率,但目前华法林临床应用不足。正在研究或已经上市的新型抗栓药物包括达比加群酯、利伐沙班和阿派沙班等可能革命性的改变这一现状。     

华法林治疗非瓣膜性房颤的效果及安全性分析

目的探讨华法林治疗非瓣膜性房颤的临床效果及安全性。方法选择患者80例,分为两组,每组各40例,观察组给予华法林口服,对照组则给予阿司匹林,比较两组患者治疗后心脏彩超的检查结果,并统计发生缺血性脑卒中、全身性栓塞、大出血的情况。结果观察组患者的左室射血分数显著高于对照组（P〈0．05）,发生缺血性脑卒中、全身性栓塞、大出血的比例显著低于对照组（P〈0．05）。结论华法林抗凝可预防老年非瓣膜性房颤发生脑卒中、血管栓塞及大出血。提高心脏射血分数。