Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks

 

Abstract

Background

Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke mediated by embolism of stasis-precipitated thrombi from the left atrial appendage.

Objectives

To characterize the efficacy and safety of oral anticoagulants (OACs) for the primary prevention of stroke in patients with chronic AF.

Search methods

We searched the Cochrane Stroke Group Trials Register (last searched in June 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to June 2004), and the reference lists of recent review articles. We also contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials.

Selection criteria

All randomized controlled trials comparing OACs with control in patients with chronic non-valvular atrial fibrillation and no history of transient ischemic attack (TIA) or stroke.

Data collection and analysis

Trials for inclusion were independently selected by two authors who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, intention-to-treat. Since the published results of four trials included 3% to 8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators.

Main results

Of 2313 participants without prior cerebral ischemia from five randomized trials, the mean age was 69 years. Participant features and study quality were similar between trials: the OAC in all five trials was warfarin. About half of participants (N = 1154) were randomized to adjusted-dose warfarin with mean achieved INRs ranging between 2.0 to 2.6. During 1.5 years mean follow up, warfarin was associated with large, highly statistically significant reductions in all strokes (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.26 to 0.59), ischemic stroke (OR 0.34, 95% CI 0.23 to 0.52), all disabling or fatal stroke (OR 0.47, 95% CI 0.28 to 0.80), death (OR 0.69, 95% CI 0.50 to 0.94) and the combined endpoint of all stroke, myocardial infarction or vascular death (OR 0.56, 95% CI 0.42 to 0.76). The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy, but the confidence intervals were wide.

Authors' conclusions

Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke, disabling or fatal stroke, and death for patients with non-valvular AF. The benefits were not substantially offset by increased bleeding among these participants in randomized clinical trials. Limitations include relatively short follow up and imprecise estimates of bleeding risks from the selected participants enrolled in the trials. For primary prevention of stroke in AF patients, about 25 strokes and about 12 disabling or fatal strokes would be prevented yearly for every 1000 atrial fibrillation patients given OACs.

 

Plain language summary

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks

Oral anticoagulants prevent stroke and death in people with atrial fibrillation. Atrial fibrillation is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the blood stream to the brain and cause a stroke. Anticoagulant drugs, such as warfarin, slow blood clotting. The degree of inhibition of blood clotting during warfarin treatment is measured by a blood test called the international normalized ratio (INR). Dosages of warfarin that lead to INRs of 2.0 to 2.6 reduce death and stroke when given to patients with atrial fibrillation. Oral anticoagulants can cause bleeding into the brain and elsewhere. However, provided that there is careful control of dosage (requiring INR measurements at least monthly with warfarin), the risk of serious bleeding is low. The decision about whether or not to use oral anticoagulants in patients with atrial fibrillation is guided by a number of factors, including the individual's risk of stroke, which varies widely among patients with atrial fibrillation. Most people with atrial fibrillation should be considered for treatment with oral anticoagulants based on their risk of stroke, ability to tolerate anticoagulation without bleeding, and access to adequate anticoagulation monitoring.

 

摘要

背景

口服抗凝血劑用於非瓣膜性心房顫動且先前無中風或暫時性腦缺血病史之病人以預防中風

非瓣膜性心房顫動(AF)會增加由左心房附體中因血液停滯促生的血栓導致之栓塞性中風的風險。

目標

此目的是描述口服抗凝血劑(OACs)用於慢性AF病人作為中風初級預防的效力與安全性。

搜尋策略

我們搜尋Cochrane Stroke Group Trials Register(搜尋至2004年6月)。此外，我們搜尋Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004)， MEDLINE (1966年至2004年6月)，以及最近的回顧論文之參考索引。我們並聯絡 Atrial Fibrillation collaboration 與在此領域工作的專家以確認未發表和進行中的試驗。

選擇標準

比較OACs與對照組用於慢性非瓣膜性心房顫動且無暫時性腦缺血(TIA)或中風病史之病人的所有隨機對照試驗(randomized controlled trial)。

資料收集與分析

兩位作者各自選擇要被納入的試驗，篩選每一個預後因子並核對資料。Peto方法被用來合併勝算比(odds ratio)。所有的分析方法，只要可能的話，是治療意向分析(intentiontotreat)。既然已發表的4個試驗中包括了3%至8%的參與者是先前有過中風或TIA的，尚未發表的部份則經由Atrial Fibrillation Investigators取得排除那些參與者的結果。

主要結論

在5個隨機試驗中的2313位先前沒有腦缺血的參與者，其平均年齡為69歲。參與者的特徵與研究品質在各試驗間是相似的：在所有5個試驗中的OAC都是warfarin。約有一半的參與者(n = 1154)被分派給予調整過劑量的warfarin使得達到的INRs平均介於2.0到2.6之間。在平均1.5年的追蹤期內，warfarin在所有的中風(OR 0.39，95%　CI　0.26 to 0.59)，缺血性中風(OR 0.34, 95% CI 0.23 to 0.52)，所有致殘或致死性中風(OR 0.47, 95% CI 0.28 to 0.80)，死亡(OR 0.69, 95% CI 0.50 to 0.94)，以及所有中風、心肌梗塞或血管因素的死亡的合併終點(OR 0.56, 95% CI 0.42 to 0.76)上，造成了統計學上相當顯著的降低。觀察到的顱內與顱外出血機率並沒有因OACs治療而顯著增加，但信賴區間很寬。

作者結論

使用調整劑量的warfarin治療以使得INRs達到2至3，減少了非瓣膜性AF病人的中風、失能或致死性中風，以及死亡。此利益在隨機臨床試驗中的這些參與者中，實質上並沒有因為增加的出血而抵銷。在限制方面包括了相對短暫的追蹤時間以及在選擇加入這些試驗的參與者時並沒有精確地評估出血風險。針對AF病人的中風初級預防，使用OACs的每1000名心房顫動的病人中，約有25件中風與約12件致殘或致死性中風可以被避免。

翻譯人

本摘要由奇美醫院陳軾正翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

口服抗凝血劑用於心房顫動的病人可預防中風與死亡。心房顫動是一種不規則的心跳，導致血栓形成在心臟的上部腔室(心房)。這些血栓可能脫落並隨著血流到達腦部並造成中風。抗凝血劑，例如warfarin，減緩了血液凝固。在wafarin治療期間其抑制血液凝固的程度是用一種名為international normalized ratio (INR)的血液測試來測量的。給予心房顫動的病人wafarin使其劑量讓INR達到2.0到2.6之間，減少了死亡與中風。口服抗凝血劑可能造成腦部或其他地方出血。然而，如果有仔細地控制劑量(使用warfarin時最少需要每個月測量一次INR)，嚴重出血的風險是很低的。針對是否給予心房顫動病人使用口服抗凝血劑的決定受到一些因素的指引，包括個人中風的風險，而其在不同的心房顫動病人間有很大的變異。大多數的心房顫動病人應該根據他們中風的風險、耐受抗凝血劑而不會出血，以及適當監控抗凝血劑使用的能力，來考慮使用口服抗凝血劑治療。