Clopidogrel hydrogen sulphate for atrial fibrillation

INTRODUCTION: Atrial fibrillation is a common cardiac rhythm abnormality with a considerable cardiovascular disease burden worldwide. It is an independent major risk factor for stroke. Stroke prevention with anticoagulation or antiplatelet agents has been an important area of clinical research. Warfarin is the most widely used antithrombotic therapy for stroke prophylaxis for last several years, and now dabigatran (150 mg b.i.d.) is more effective than warfarin in stroke prevention in individuals at increased of stroke. In addition, several studies have evaluated the efficacy of clopidogrel for stroke prophylaxis either alone or in combination with aspirin. AREAS COVERED: This review summarizes the key findings of the trials looking at the efficacy of clopidogrel in stroke prevention. A literature search was performed using PubMed and Google Scholar. The trials that evaluated the efficacy of clopidogrel in preventing atherothrombotic events or stroke were also included. EXPERT OPINION: Clopidogrel prevents more vascular events, including stroke, in patients with a recent myocardial infarction, stroke or peripheral vascular disease than aspirin. Combination of clopidogrel and aspirin provides a greater reduction of stroke than aspirin or clopidogrel monotherapy, but at an increased risk of bleeding. Dual antiplatelet therapy (clopidogrel and aspirin) is inferior to warfarin in primary stroke prevention for patient with atrial fibrillation and thus should be considered for stroke prophylaxis only in patients ineligible for warfarin. However, with the advent of newer agents, like direct thrombin inhibitors and Factor Xa inhibitors, the role of antiplatelet therapy for stroke prevention in atrial fibrillation remains unclear.     

Stroke prevention in atrial fibrillation patients

Importance of the field: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice and is associated with an increased risk of stroke, mortality and significant morbidity. Given the rapidly increasing incidence and prevalence of AF, and the resulting public health burden of the consequences associated with this arrhythmia, stroke prevention is an extremely important topic.

Areas covered in this review: This review covers the epidemiology of AF, the pathophysiology of ischemic stroke in AF and current antithrombotic therapy choices for stroke prevention in this condition. In addition, this article discusses important topics such as the assessment of stroke risk stratification and bleeding risk assessment, which are key issues in deciding upon thromboprophylaxis for AF patients. Finally, the review highlights the advent of new anticoagulant therapies and discusses the future challenges for researchers in this area.

What the reader will gain: This review summarizes all of the major antithrombotic trials conducted in AF patients over the last twenty years and highlights the importance of anticoagulation therapy for the prevention of stroke, after appropriate individual stroke and bleeding risk assessment.

Take home message: Assessment of individual stroke risk and bleeding risk is key in determining appropriate thromboprophylaxis for AF patients, given the associated thromboembolic and hemorrhagic complications. The availability of newer, safer and more convenient drugs will mean that oral anticoagulation is available for a larger proportion of AF patients who may benefit from it.     

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Abstract

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.

Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6?years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.

Results: The study included 2494 patients (age = 76.0?±?9.5?years, CHA₂DS₂-VASc = 4.0?±?1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1?±?10.3 years), with better kidney function (mean CrCl = 80.6?±?35.8?ml/min) and lower CHA₂DS₂-VASc (3.7?±?1.4) and HAS-BLED (2.1?±?0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3?±?1.6 and 2.6?±?0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p?<?.001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.

Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).     

达比加群酯预防房颤患者卒中的临床研究

目的 观察达比加群酯预防房颤患者卒中的疗效及安全性。方法 纳入房颤患者80例均符合抗凝治疗指征。按照奇偶数法随机分为观察组（n=40）和对照组（n=40）。观察组给予达比加群酯110 mg,2次/d;对照组给予华法林2.5 mg/d,并定期测定国际标准化比值（INR）,根据INR调整剂量。两组疗程均为6个月。记录两组患者卒中、全身性栓塞和大出血发生情况。两组患者出院时检查凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）和D-二聚体等凝血指标。结果 观察组患者卒中/全身性栓塞的发生率为17.5%,对照组为37.5%,两组患者卒中/全身性栓塞发生率有统计学差异（P<0.05）;观察组患者大出血发生率显著低于对照组,差异有统计学意义（P<0.05）。两组患者凝血功能指标差异均无统计学意义。治疗后,两组血脂水平均较治疗前显著改善,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组血脂水平改善更为明显,组间差异有统计学意义（P<0.05）。结论 与华法林比较,对有房颤患者行抗凝治疗达比加群酯具备同等疗效,且安全性更高。     

Warfarin and aspirin as thromboprophylaxis in atrial fibrillation

1 Anticoagulant therapy with warfarin is now established as effective thromboprophylaxis against stroke in atrial fibrillation, in high-risk persons. Aspirin is indicated in moderate-risk persons or if warfarin is contraindicated.
2 Risk stratification is suggested, using clinical factors supplemented by echocardiography, to aid choice of prophylaxis.
3 Further studies are required to establish how best to identify undiagnosed patients who have atrial fibrillation; to develop new therapeutic strategies; and to refine risk stratification to define which patients with atrial fibrillation are at the highest risk of stroke.     

阵发性心房颤动与血浆硫化氢水平的相关性研究

目的：观察阵发性心房颤动患者血浆硫化氢(H2S)水平变化,研究其与阵发性心房颤动的相关性。方法50例阵发性心房颤动患者作为病例组,50例健康受试者作为对照组,采用去蛋白法测定血清H2S水平。结果病例组血浆H2S水平(28.63±12.74)μmol/L显著低于对照组(49.21±10.95)μmol/L (P<0.01)。结论阵发性心房颤动的发生可能与患者血浆H2S水平的降低有关。     

治疗心房纤颤和扑动的新药决奈达隆

决奈达隆为胺碘酮的类似物,结构中不含碘,减少了碘所致的器官毒性,为新型的抗心律失常药。2009年7月1日获FDA批准,用于治疗心房纤颤或心房扑动的心脏病患者。本文通过对决奈达隆进行文献检索,对其药理作用、药动学、临床评价、药物相互作用、不良反应等方面进行了综述。     

心房颤动的导管消融治疗

心房颤动是临床最常见心律失常之一,可显著增加心血管事件的发生率和死亡率.近年来房颤导管消融治疗在房颤治疗中的地位不断提升,有越来越多的新技术及新术式被用于临床.尽管存在着心脏压塞、肺静脉狭窄等并发症,但导管消融治疗的安全性和有效性已得到多项研究证实,现已逐渐成为房颤的主要治疗手段之一.该文对房颤导管消融治疗的机制、消融技术、手术方法及并发症综述如下.     

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。     

Effectiveness and safety of rivaroxaban in nonvalvular atrial fibrillation: data from a contemporary Spanish registry

Objective: To ascertain the clinical profile, management and rates of thromboembolic and bleeding complications in a contemporary cohort of patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban treatment, with a particular focus on some subgroups of patients.

Methods: Retrospective study that included all NVAF patients who started treatment with rivaroxaban for the prevention of stroke or systemic embolism between December 2012 and December 2015. Rates of outcomes (stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death) during follow-up were calculated.

Results: A total of 732 patients (mean age 76.4?±?9.2?years; 54.5% women) were included. Comorbidities were common (hypertension 87.5%; diabetes 26.5%; renal insufficiency 24.6%; prior stroke/transient ischemic attack 16.8%). Mean CHA₂DS₂-VASc was 3.9?±?1.5 and HAS-BLED 2.3?±?0.9; 61.9% of patients were rivaroxaban naïve users. After a mean treatment period of 22.7?±?7.4?months, rates of stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death were 1.8, 1.0, 3.2, 0.4 and 5.5 events per 100 patient-years, respectively. Rates of stroke and death were higher in patients >75?years (vs. ≤75?years) and in patients with prior stroke/transient ischemic attack or renal insufficiency. Rates of major bleeding were higher among patients >75?years and in patients with prior stroke/transient ischemic attack.

Conclusions: In this contemporary Spanish cohort of NVAF patients on rivaroxaban, patients had many comorbidities, a high thromboembolic risk and a moderate bleeding risk. Overall, rates of stroke and bleeding complications were low and similar to other previous studies. These data suggest that rivaroxaban is effective and safe in routine practice.     

Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence

Objectives: Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial).

Methods: Medical claims and Electronic Health Records were retrieved retrospectively from Optum’s Integrated Claims–Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts.

Results: Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR?=?0.41 [0.21–0.80], p?=?.009). Rivaroxaban patients with an eCrCl below 50?mL/min (N?=?229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N?=?647) was 6.0 per 100 PY (HR?=?0.09 [0.01–0.72], p?=?.02). For the other renal function levels (i.e. eCrCl 50–80 and ≥80?mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function.

Conclusions: Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50?mL/min. For all renal function groups, major bleeding risks were not statistically different between treatment groups.     

Considerations and treatment options for patients with comorbid atrial fibrillation and diabetes mellitus

Introduction: Atrial fibrillation (AF) and diabetes mellitus (DM) are common worldwide and their incidence is increasing, representing a significant public health and economic burden as well as an increase in individual increased morbidity and mortality risk profiles. Both conditions are closely related, as patients with DM are at increased risk of incident AF, and AF patients with DM are at higher risk of cardiovascular events compared to non-AF patients.

Areas covered: This review article aims to provide an overview of the current evidence linking DM and AF, as well as the impact of obesity, weight loss and stroke on these coexisting conditions. Second, the effects of new oral anti hyperglycaemic medications on cardiovascular risk will be considered.

Expert opinion: In conclusion, coexisting AF and DM represent a high risk population of patients requiring aggressive risk factor identification and treatment optimisation. The multifactorial interplay between these conditions requires individual assessment of patient risk profiles with the aim of minimising the impact of each modifiable risk factor.     

辛伐他汀对心房颤动患者左房内径影响的研究

目的：探讨辛伐他汀对心房颤动患者左房内径（LAD）的影响。方法：选取确诊的房颤患者56例,随机分为辛伐他汀干预组（28例）和对照组（28例）。分别于入院时及随访6个月后测量LAD。结果：辛伐他汀干预组入院时（43.73±4.33）mm与随访后（40.86±3.80）mm的LAD比较,差异有统计学意义（P〈0.05）,而对照组二者差异无统计学意义（P〉0.05）;辛伐他汀干预组（40.86±3.80）mm和对照组（44.18±3.73）mm随访后的LAD比较,差异有统计学意义（P〈0.05）。结论：辛伐他汀可以有效防治心房颤动患者LAD增大,有望成为房颤治疗的新途径。     

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.

Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.

Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.     

非瓣膜性房颤患者脑梗死急性期抗凝治疗时机分析

目的:调查济宁医学院附属医院非瓣膜性房颤患者脑梗死急性期启动抗凝治疗的时机,为抗凝策略提供参考.方法:采取回顾性病例研究方法,抽取该院2019年1月1日至2019年12月31日出院、诊断为急性脑梗死(或短暂性脑缺血发作)和非瓣膜性房颤的患者为研究对象,记录患者启动抗凝治疗距脑梗死症状出现的时间,并采集相关的临床资料.分...     

New anticoagulants for venous thromboembolism and atrial fibrillation: what the future holds

Introduction: The field of anticoagulation has seen impressive progress over the last decade. The introduction of the Non Vitamin K Oral Anticoagulants (NOACs) has revolutionized practice surrounding thromboprophylaxis, treatment of thromboembolic disease and stroke prevention in atrial fibrillation (AF). However, the search for the ‘holy grail’ of anticoagulation, an agent that combines optimal efficacy with minimal bleeding diathesis, continues.

Areas covered: In this paper we aim to summarize the current evidence from pre-clinical studies and early phase clinical trials, presenting the pharmacodynamic and pharmacokinetic properties as well as the safety and efficacy profiles of the most important antithrombotic agents in development.

Expert opinion: Research focused on the development of new anticoagulation agents is rapidly expanding. Although the exploration of antithrombotic agents that act on well-established targets such factor Xa and thrombin remains the mainstay, attention has also shifted to other factors in the coagulation cascade. The evidence emerging from clinical research is growing, generating exciting possibilities in the field of anticoagulation.     

Drug-induced atrial fibrillation

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and an important cause of hospitalization, morbidity, and mortality. A myriad of drugs can induce AF. However, drug-induced AF (DIAF) receives little attention. Thus, this review is an attempt to attract the attention on this adverse effect.

Areas covered: Published reports of drug-induced AF (DIAF) are reviewed in this paper, from January 1974 to December 2011, using the PubMed/Medline database and lateral references.

Expert opinion: In most cases, DIAF is paroxysmal and terminates spontaneously, but sometimes AF persists and it is necessary to perform a cardioversion to restore sinus rhythm and avoid progression to persistent AF. Because of the short duration of DIAF, in addition to physicians/patients not being knowledgeable about this side effect, the real incidence and clinical consequences of DIAF are presently unknown. DIAF is an increasing problem, as some widely prescribed drugs can present this adverse effect. The risk is expected to increase in the elderly and in patients with comorbidities. It is important that physicians understand the significance of DIAF, to increase the collaboration between cardiac and non-cardiac professionals, and to educate patients to make them aware of this adverse side effect.     

Drug therapy for atrial fibrillation

Although the maintenance of sinus rhythm would be the ideal scenario for patients with atrial fibrillation (AF), recent randomised trials have questioned the value of this approach. A careful interpretation of their results showed the limited efficacy of currently available antiarrhythmic drugs in maintaining sinus rhythm, as well as their potentially serious side effects. Therefore, it is imperative to develop safer and more effective drugs for AF. Based on our improved understanding of the pathophysiology of AF and the mechanism of action of antiarrhythmic drugs, significant efforts are being made to develop new antiarrhythmic agents that would prevent electrophysiological remodelling, would be selective for the atria and, therefore, would not prolong ventricular repolarisation, thus lacking any proarrhythmic effect.     

New evidences for old concerns with oral anticoagulation in atrial fibrillation: focus on dabigatran

Introduction: Nonvalvular atrial fibrillation (NVAF) is associated with a fivefold excess risk of stroke. Antithrombotic therapy is crucial to reduce the risk of stroke. During past decades, vitamin K antagonists (warfarin or acenocoumarol) have been widely used for this purpose. However, they have several disadvantages that limit their daily use in clinical practice.

Areas covered: In patients with NVAF at risk of stroke, the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial demonstrated that, compared with warfarin, dabigatran 150 mg b.i.d. was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage, whereas dabigatran 110 mg b.i.d. exhibited similar rates of stroke and systemic embolism, but lower rates of major hemorrhage. Fortunately, data about dabigatran are not limited to RE-LY trial. In fact, many substudies have been drawn, providing new and important evidences about the benefits of dabigatran.

Expert opinion: The most recent evidences about efficacy and safety of dabigatran in patients with NVAF, focusing on different substudies of RE-LY trial, are reviewed. In summary, dabigatran is beneficial not only in general population with NVAF but also in different subgroups of patients or different clinical settings (i.e., CHADS2 score, INR control, type of AF, elderly, previous transient ischemic attack or stroke, cardioversion and so on).