Stroke prevention in atrial fibrillation

Nonvalvular atrial fibrillation (AF) is an independent risk factor for stroke. The overall risk of ischemic stroke in patients experiencing AF without prior stroke averages about 5% per year, but varies depending on the presence of coexistent thromboembolic risk factors. Patients with AF with low (about 1% per year), moderate (2%–4% per year) and high (≥ 6% per year) stroke risks have been identified, but the generalizability of available risk stratification schemes to clinical practice has not been defined. Adjusted-dose warfarin (target International Normalized Ratio [INR] 2–3) is highly efficacious for prevention of stroke in patients with AF (about 60% reduction) and is relatively safe for selected patients, if carefully monitored. Aspirin has a modest effect on reducing stroke (about 20% reduction). The role of transesophageal echocardiography is routine management of AF remains unsettled. Warfarin therapy should be considered for patients with AF predicted to have a high risk of stroke and who can safely receive it. Aspirin may be indicated for patients with AF at low risk for stroke and for those who cannot safely receive adjusted-dose warfarin. For those with moderate stroke risk, individual bleeding risks during anticoagulation and patient preferences should guide antithrombotic therapy.     

The impact of warfarin use on clinical outcomes in atrial fibrillation: a population-based study

BACKGROUND: Atrial fibrillation (AF) is the most common adult arrhythmia, and significantly increases the risk of ischemic stroke. Oral anticoagulation may be underused and may be less effective in community settings than clinical trial settings. OBJECTIVES: To determine the rates of thromboembolism and bleeding in an ambulatory cohort of patients with AF. METHODS: Observational study of Nova Scotian residents with AF identified by electrocardiogram in ambulatory settings between November 1999 and January 2001. Main outcome measures were rates of thromboembolism and bleeding over two years. RESULTS: Four hundred twenty-five patients were included in the study. The mean (+/-SD) age was 70.6+/-11.1 years, and 40% were women. Warfarin therapy was used by 68% of patients. Sixty-two per cent of patients had hypertension, 21% had a previous stroke or transient ischemic attack, 44% had congestive heart failure and 20% were diabetic. The overall rate of thromboembolic events was 2.7% in warfarin users and 8.5% in nonwarfarin users over two years, with an RR reduction of 68% (OR 0.31, 95% CI 0.09 to 0.91; P=0.047). The annual rate of ischemic stroke was 1.2% and 3.1% in warfarin and nonwarfarin users, respectively, with an RR reduction of 62% (OR 0.29, 95% CI 0.08 to 1.04; P=0.057). The overall rate of major bleeding was 2.6% in warfarin users and 1.4% in nonwarfarin users (P=0.667). The annual mortality rate was 7.79% in warfarin users and 9.93% in nonwarfarin users (P=0.192). CONCLUSIONS: Warfarin use was found to significantly reduce the rate of thromboembolic events without a concomitant increase in hemorrhagic events. The present study confirms the effectiveness of warfarin therapy in a population-based cohort.     

A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO)

BACKGROUND: atrial fibrillation (AF) is the commonest chronic arrhythmia with a prevalence of 9% in octogenarians and accounts for 24% of the stroke risk in this population. Although trials demonstrate reductions in stroke with warfarin, audit data show that it is still underused. However, anti-coagulation in the very elderly is not without risk. METHODS: randomised open labelled prospective study of primary thromboprophylaxis for AF. Patients aged >80 and <90 were randomised to receive dose-adjusted warfarin (INR 2.0-3.0) or aspirin 300 mg. All patients had permanent AF, were ambulant, had Folstein mini mental score >25 and had no contraindications to either treatment. Follow-up was for 1 year with 3 monthly visits. The primary outcome measure was a comparative frequency of combined endpoints comprising death, thromboembolism, serious bleeding and withdrawal from the study. RESULTS: seventy-five patients (aspirin 39; warfarin 36) were entered (mean age 83.9, 47% male). There were significantly more adverse events with aspirin (13/39; 33%) than warfarin (2/36; 6%), P = 0.002. 10/13 aspirin adverse events were caused by side effects and serious bleeding; there were three deaths (two aspirin, one warfarin). CONCLUSION: dose-adjusted warfarin was significantly better tolerated with fewer adverse events than aspirin 300 mg in this elderly population. Although aspirin 75 mg may have been better tolerated, there is no evidence for efficacy in AF at this dose.     

华法林与阿司匹林预防非瓣膜性心房颤动患者血栓栓塞的随机对照研究

目的通过前瞻性、随机、多中心研究比较阿司匹林与调整剂量华法林预防非瓣膜性心房颤动(房颤)患者发生血栓栓塞的有效性和安全性。方法在18个中心,根据入选标准将非瓣膜性房颤患者随机分配至阿司匹林组(150~160mg/d)和调整剂量华法林组(初始剂量2mg/d),目标国际标准化比值(INR)为2·0~3·0(年龄≥75岁者的INR为1·6~2·5)。常规门诊随访,调整华法林剂量并记录两组患者的终点事件和不良反应发生情况。主要终点事件为缺血性脑卒中和死亡,次要终点事件包括短暂性脑缺血发作、腔隙性脑梗死、外周动脉栓塞、急性心肌梗死和严重出血。结果共704例患者进入分析,阿司匹林组369例,华法林组335例。男性420例(59·7%),平均年龄(63·3±9·9)岁,两组患者基线特征(包括合并疾病和伴随用药)差异无统计学意义。随访时间中位数19个月(2~24个月)。与阿司匹林比较,调整剂量华法林明显降低主要终点事件发生率[2·7%比6·0%,P=0·03,OR0·44,95%可信区间(CI)为0·198~0·960],相对危险下降54%;缺血性脑卒中的相对危险下降62%(1·8%比4·6%,P=0·04,OR0·38,95%CI为0·147~0·977);总血栓栓塞事件相对危险下降52%(10·6%比5·4%,P=0·01,OR0·48,95%CI为0·269~0·858)。次要终点事件两组间差异无统计学意义。华法林组轻微出血和严重出血发生率均高于阿司匹林组(P<0·05)。华法林组总死亡率低于阿司匹林组[4例(1·2%)比8例(2·2%)],但差异无统计学意义(P>0·05);包括主要和次要终点的联合终点事件华法林组低于阿司匹林组(8·4%比13·0%,P=0·047)。结论与阿司匹林相比,华法林可明显降低国人非瓣膜性房颤患者脑卒中的发生率,华法林组出血的发生率高于阿司匹林组,但多数出血并发症发生在INR>3·0。严密监测(INR2·0~3·0)下的调整剂量华法林安全有效。     

高龄非瓣膜性房颤的华法林治疗11例体会

目的:探讨华法林治疗高龄非瓣膜性房颤患者安全有效的抗凝强度。方法:对11例高龄非瓣膜房颤有抗凝适应证者予华法林治疗,将抗凝强度控制在INR为1.5~2.0,观察疗效和出血并发症。结果:观察期间11例患者无致命性出血,仅1例皮肤出血且未停药。7例患者反复发作的短暂性脑缺血发作和脑梗塞症状得到控制。3例有2种以上危险因素的患者未出现栓塞并发症。结论:低抗凝强度(INR1.5~2.0)抗凝对高龄非瓣膜性房颤患者安全有效。     

Prevention of stroke in patients with atrial fibrillation

Nonvalvular atrial fibrillation (AF) is an independent risk factor for stroke that becomes increasingly prevalent as populations age. More than half a dozen clinical trials have demonstrated that anticoagulation with the vitamin K antagonist warfarin is the most effective therapy for stroke prophylaxis in AF. The narrow therapeutic index of warfarin requires that the intensity of anticoagulation be maintained within the international normalized ratio (INR) range of 2.0 to 3.0 to optimize efficacy while minimizing bleeding risk. The pharmacokinetics of warfarin are subject to variability due to interactions with multiple drugs and foods, making maintenance of the INR within this range difficult to achieve in clinical practice without close coagulation monitoring and frequent dose adjustments. Current guidelines recommend oral anticoagulation for high-risk individuals with AF but these inherent limitations lead to substantial underprescribing, particularly in elderly patients at greatest risk. This has stimulated the development of new agents with improved benefit-risk profiles, such as ximelagatran, the first of the oral direct thrombin inhibitors, which has a wider therapeutic margin and low potential for drug interactions, allowing fixed dosing without anticoagulation monitoring. Ximelagatran has been evaluated for stroke prevention in AF in the Stroke Prevention using an Oral Direct Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) program, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials of ximelagatran in AF, SPORTIF III and V, found a fixed oral dose of ximelagatran (36 mg twice daily) comparable to dose-adjusted warfarin (INR 2.0 to 3.0) in preventing stroke and systemic thromboembolic complications among high-risk patients with AF. Results from the population of over 7000 patients in SPORTIF III and V demonstrate noninferiority of ximelagatran compared with warfarin. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin of 1.6% per year versus 2.3% per year, respectively ( P = 0.10). SPORTIF V further supports noninferiority between the two agents with an absolute risk reduction of 0.45%, well within the predefined noninferiority margin (95% confidence interval -0.13, 1.03; P = 0.13). Although event rates for major bleeding did not differ significantly with ximelagatran versus warfarin in either study, combined rates for major and minor bleeding were significantly reduced with ximelagatran. The overall net clinical benefit, taking into account effects on stroke or systemic embolic events, major bleeding, and death, was also greater with ximelagatran compared with warfarin in both studies. Elevated serum transaminase enzymes were observed in approximately 6% of patients given ximelagatran in these trials. These typically occurred 1 to 6 months after initiating treatment and usually abated without clinical sequelae whether or not treatment was continued. Given the consistency of response, the favorable overall benefit-risk ratio and the convenience of fixed oral dosing, ximelagatran may increase the number of patients with AF eligible for anticoagulation and amplify the potential for prophylaxis against stroke.     

Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V

BACKGROUND: Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) may be related to INR control. METHODS: We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials. The mean+/-SD follow-up was 16.6 +/- 6.3 months. Patients were divided into 3 equal groups (those with good control [>75%], those with moderate control [60%-75%], or those with poor control [<60%]) according to the percentage time with an INR of 2.0 to 3.0. Outcomes were compared according to INR control. The main outcome measures were death, bleeding, MI, and stroke or SEE. RESULTS: The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good control group (1.69% and 1.58%, respectively) (P<.01 for all). Compared with the good control group, the poor control group had higher rates of MI (1.38% vs 0.62%, P = .04) and of stroke or SEE (2.10% vs 1.07%, P = .02). CONCLUSIONS: In patients with atrial fibrillation taking warfarin, the risks of death, MI, major bleeding, and stroke or SEE are related to INR control. Good INR control is important to improve patient outcomes.     

Efficacy and safety of aspirin,clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS₂ score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02–59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan–Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.     

Warfarin use and long-term outcomes in patients with acute myocardial infarction and atrial fibrillation

Warfarin use in patients with acute myocardial infarction (AMI) and atrial fibrillation (AF) remains challenging. We describe use of warfarin up to 1 year after hospitalization among patients with AMI and AF according to stroke and bleeding risk, and identify factors associated with long-term mortality in this population. Patients with AMI and AF who underwent cardiac catheterization during their AMI hospitalization in 1995–2007 were identified from the Duke Databank for Cardiovascular Disease. Warfarin use at discharge, 6 months, and 1 year as well as long-term vital status were assessed by surveys. Rates of warfarin use were presented according to CHADS₂ and CHA₂DS₂VASc stroke and ATRIA bleeding risk scores. Cox proportional hazards modeling was used to determine whether warfarin use at discharge was independently associated with 1-year mortality. A total of 879 patients hospitalized with AMI with AF were identified. Median age was 72 (25th, 75th percentiles: 64, 79), and median follow-up was 4.1 years (1.3, 7.4). The rate of warfarin use at discharge was 24 % and did not differ by CHADS₂, CHA₂DS₂VASc, or ATRIA risk scores. Warfarin use remained similar at 6 months (26 %) and 1 year (27 %). Long-term mortality was high and did not differ by whether warfarin was or was not prescribed at discharge (72 and 71 %, respectively). Factors associated with 1-year mortality were history of heart failure (HR 1.58, 95 % CI 1.32–1.90), higher Charlson comorbidity index (HR 1.19, 95 % CI 1.11–1.28), and older age (HR 1.03 per 1-year increase, 95 % CI 1.02–1.05). Warfarin use at discharge among patients hospitalized for AMI who had comorbid AF was low and remained low at 1 year. Warfarin use at hospital discharge was not associated with either 1-year mortality or long-term mortality.     

Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.     

Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting.

BACKGROUND: Evidence-based clinical practice guidelines recommend the use of warfarin sodium for stroke prevention in most patients with atrial fibrillation (AF) who do not have risk factors for hemorrhagic complications, irrespective of age. METHODS: The medical records of all residents of a convenience sample of long-term care facilities in Connecticut (n = 21) were reviewed. The percentages of all patients with AF (AF patients) and ideal candidates for warfarin therapy (ie, AF patients with no risk factors for hemorrhage) who received warfarin were determined; for patients receiving warfarin, the percentage of days spent in the therapeutic range of international normalized ratio (INR) values (2.0-3.0) was also assessed. The relationship between receipt of warfarin and the presence of stroke and bleeding risk factors was assessed in multivariate models. RESULTS: Atrial fibrillation was present in 429 (17%) of the 2587 long-term care residents. Overall, 42% of AF patients were receiving warfarin. However, only 44 (53%) of 83 ideal candidates were receiving this therapy. In residents who received warfarin therapy, the therapeutic range of INR values was maintained only 51% of the time. The odds of receiving warfarin in the study sample decreased with increasing number of risk factors for bleeding and increased (nonsignificant trend) with increasing number of stroke risk factors present. CONCLUSIONS: Atrial fibrillation is very common among residents of long-term care facilities. Even among apparently ideal candidates, warfarin therapy is underused for stroke prevention in patients with AF. Prescribing decisions and monitoring related to warfarin therapy in the long-term care setting warrant improvement.     

Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation

OBJECTIVE: To determine optimal intensity of international normalized ratio (INR) of warfarin therapy for the prevention of ischemic events in patients with non-valvular atrial fibrillation (NVAF), we evaluated the risk of severe recurrent stroke, systemic embolism and major hemorrhagic complications according to INR and age. METHODS: We carried out the National Cardiovascular Center (NCVC) NVAF Secondary Prevention Study and analyzed data with those of Japanese Nonvaluvular Atrial Fibrillation-embolism Secondary Prevention Cooperative Study to elucidate relationships of major stroke and hemorrhage with INR and age. In both studies, all patients with cardioembolic stroke were given warfarin, monitored with INR every month, and followed up for primary endpoints of stroke and embolism to other parts of the body, and for secondary endpoints of major hemorrhagic complications requiring blood transfusion or hospitalization. We regarded ischemic stroke with NIH stroke scale (NIHSS) score > or = 10 or systemic embolism as a major ischemic event and ischemic stroke with NIHSS score <10 as a minor ischemic event. There were 203 patients enrolled in total (152 men and 51 women). We investigated the relationship of occurrence of the events with INR and age, and calculated the incidence rates of major and minor ischemic events and major hemorrhagic events. RESULTS: During the mean follow-up of 653 days, major ischemic stroke and systemic embolism occurred in only 4 patients with INR <1.6, minor ischemic stroke in 10 patients with INR 1.50-2.66, and major hemorrhage in 9 patients with INR 2.30-3.56. Patients with major ischemic or hemorrhagic events were significantly older than those without any events (75+/-4 years vs. 67+/-7 years, p<0.001 unpaired t test). Incidence rates of any events at INR < or = 1.59, 1.60-1.99, 2.00-2.59 and > or = 2.60 were 8.6%, 3.8%, 4.9%, and 25.7%/year, respectively. CONCLUSIONS: Major ischemic or hemorrhagic events occur often in the elderly NVAF patients, in whom an INR value of between 1.6 and 2.6 seems optimal to prevent such events.     

华法林对非瓣膜病心房颤动抗栓的安全性和有效性研究

目的观察华法林对非瓣膜病心房颤动(房颤)患者抗凝治疗的有效性和安全性。方法在18个中心进行阿司匹林(150～160 mg/d)与调整剂量华法林组随机对照研究中选取患者。华法林初始剂量2 mg/d,目标国际标准化比值(INR)2.0～3.0(年龄≥75岁者为1.6～2.5),常规门诊随访,分析该组患者终点事件和出血事件的发生及与抗凝强度的关系。结果共335例患者随机服用华法林,男204例(60.9%),年龄(62.6±10.3)岁,随访2～24个月(中位数19个月)。华法林平均剂量(3.19±0.69)mg。共进行 INR 测定3482人次,其中2378次 INR(占68.3%)维持2.0～3.0。用药期间发生主要终点事件10例(2.7%),次要终点事件19例(5.7%)。服用华法林期间总出血发生率为23例(6.9%),其中严重出血5例(1.5%),轻微出血18例(5.4%);发生血栓栓塞事件(缺血性卒中及体循环栓塞)19例(5.4%),其中15例(4.5%)患者发生事件时的 INR<2.0。多因素 logistic 回归显示,抗凝出血和血栓栓塞事件的独立危险因素均为年龄>75岁,前者收缩压≥160mm Hg,血肌酐升高,INR>3.0;后者有卒中病史,左室射血分数<0.40%和 INR<2.0。结论中国人非瓣膜病房颤患者应用华法林抗凝 INR 维持在2.0～3.0是安全有效的,但应避免 INR>3.0,以最大限度减少出血并发症,尤其应严密监测高龄、合并心力衰竭和肾功能异常的患者。     

华法林对中国人心房颤动患者抗栓的安全性和有效性研究

目的　通过回顾性分析心房颤动 (房颤 )患者的抗栓治疗 ,初步探讨中国人华法林国际标准化率 (INR)的合理范围。方法　调查 4 35例房颤患者应用华法林抗凝及INR监测情况 ,分析出血和血栓栓塞事件的危险因素及与INR的关系。结果　华法林疗程时间中位数 7个月 ,平均剂量为(2 77± 0 83)mg。共发生出血事件 31例 (7 11% ) ,其中严重出血 5例 ,轻微出血 2 6例。发生出血患者年龄略高于对照组 [(6 5 1± 10 0 )岁与 (6 2 0± 12 2岁 ) ],但差异无统计学意义 (P =0 2 5 9) ;出血患者血压高于对照组 ,合并心力衰竭较多 (P =0 0 5 )。多因素分析中INR≥ 3为预测出血的独立危险因素 (OR =3 74 )。血栓栓塞事件 37(17 4 7% )例 ,发生缺血性卒中或栓塞的危险随INR下降明显增加。结论　房颤患者华法林抗凝目标INR值应避免低于 1 5或高于 3 0。     

Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients

Atrial fibrillation (AF) affects 2.5 million patients in the United States. The incidence of this condition increases with age, such that approximately 5% of people > 65 years of age have AF. Because of the lack of organized atrial contraction and thrombus formation in the left atrium, patients with AF are at increased risk of stroke. The estimated risk of stroke among all AF patients is 5% per year. Among patients without mitral stenosis, there is a graded relationship of stroke risk with the number of CHADS? risk factors. Warfarin is the recommended treatment for embolic stroke prophylaxis in AF in intermediate- to high-risk patients. However, elderly patients who are deemed to be at risk of falls are often not started on warfarin therapy secondary to a perceived higher risk of bleeding complications. These risks have been evaluated, but conclusive data regarding the risk-benefit trade-off are elusive. This review summarizes available data on the use of warfarin in elderly patients with AF, focusing on the risk of bleeding, and will specifically address the utility of falls risk assessment in the decision to initiate warfarin therapy for AF.     

Rivaroxaban vs. Warfarin in Japanese Patients With Atrial Fibrillation

Background:?The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. Methods and Results:?J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). Conclusions:?J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice. (Circ J?2012; 76: 2104-2111).     

老年心房颤动高危患者抗凝治疗的药物选择及安全性

目的探讨老年心房颤动患者抗凝治疗的药物剂量选择及安全性。方法选择确诊的老年心房颤动患者210例,按照年龄将60～79岁130例作为老年段及≥80岁80例作为高龄段。2个年龄段患者按服药治疗不同分为老年华法林组30例、高龄华法林组30例,老年联合用药组50例(氯吡格雷75 mg+阿司匹林100 mg),老年阿司匹林组50例和高龄阿司匹林组50例(阿司匹林100 mg)。观察服用华法林剂量及国际标准化比值(INR);各组患者栓塞及出血发生率。结果高龄华法林组剂量(2.88±0.46)mg,INR 2.29±0.55,老年华法林组剂量(2.93±0.75)mg,INR 2.30±0.52,差异无统计学意义(P>0.05)。老年华法林组和高龄华法林组及老年联合用药组栓塞发生率明显低于老年阿司匹林组和高龄阿司匹林组(P<0.05)。与老年华法林组和高龄华法林组及老年阿司匹林组和高龄阿司匹林组比较,老年联合用药组出血发生率明显高(P<0.05)。结论老年心房颤动患者服用华法林或氯吡格雷+阿司匹林能更有效预防脑卒中事件的发生,老年、尤其是高龄高危患者服用华法林治疗,INR控制在1.5～2.5是安全、有效。对于不适合应用华法林的患者,可应用氯吡格雷+阿司匹林预防血栓形成。     

不同抗凝强度华法令预防非瓣膜病心房颤动患者血栓栓塞(附212例临床观察)

目的　探讨不同抗凝强度华法令预防非瓣膜病心房颤动 (Af)患者血栓栓塞事件的效果及其不良反应。方法　 2 12例非瓣膜病Af患者随机分为两组 ,分别给予华法令抗凝强度国际标准化比率 (INR) 1 80～2 . 4 0 (低等强度 ,12 3例 )和INR2. 4 1～ 3 .0 0 (中度强度 ,89例 )抗凝治疗。观察两组血栓栓塞并发症及出血等不良反应发生率。结果　低等强度抗凝组血栓栓塞年发生率为 0 . 6 6 % ,与中等强度抗凝组的 0 13%比较无显著差异 (P >0 . 0 5 )。低强度抗凝组的出血不良反应年发生率为 2 .4 % ,明显低于中等强度抗凝组的 7 9% (P <0 . 0 5 ) ,但两组均未见严重出血及其他严重不良反应。结论　华法令抗凝强度 1. 80～ 3. 0 0能明显降低非瓣膜病Af患者血栓栓塞发生率。INR 2 . 4 1～ 3 .0 0时自发出血危险性增加。     

Apixaban in patients with atrial fibrillation and prior coronary artery disease: Insights from the ARISTOTLE trial

Background

A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD.

Methods and results

In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71–1.27, P for interaction = 0.12; HR 0.96, 95% CI 0.81–1.13, P for interaction = 0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD.

Conclusions

In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.