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抗凝關鍵時刻：了解維生素K拮抗劑治療何時該用、用對人

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22
4 月

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維生素K拮抗劑（如華法林）是預防血栓的核心藥物，特別適用於機械瓣膜、心房顫動等高風險患者。正確評估中風與出血風險並設定INR目標，是確保療效與安全的關鍵。

Indications for vitamin K antagonist therapy

維生素 K 拮抗劑治療的適應症

https://diagnostics.roche.com/global/en/article-listing/indications-pt-inr.html

了解何時維生素 K 拮抗劑療法對我的病人有益。
Understanding when vitamin K antagonist therapy is beneficial for my patients.

雖然止血對生存是必要的，但病理性血栓形成或血栓症卻帶來重大健康風險。
While hemostasis is necessary for survival, the pathological formation of a blood clot, or thrombosis, poses significant health risks.

病人接受維生素 K 拮抗劑（VKA）的主要適應症如下：
The main indications for a patient to receive vitamin K antagonists (VKAs) are the following:

  • 機械心臟瓣膜  Mechanical heart valves
  • 心房顫動  Atrial fibrillation
  • 深靜脈血栓和肺栓塞
    Deep vein thrombosis and pulmonary embolism
  • 心肌梗塞  Myocardial infarction
  • 急性缺血性中風  Acute ischemic stroke

 

機械心臟瓣膜 Mechanical heart valves

由於更換任何帶有機械假體的瓣膜後血栓栓塞併發症的風險增加，因此永久抗凝治療是合理的。 1,2 大多數心臟瓣膜缺陷是在生命後期獲得的，並且是由於退行性心臟瓣膜疾病造成的。當遺傳性或獲得性缺陷嚴重限制瓣膜功能時，心臟瓣膜置換變得必要。

Permanent anticoagulation therapy is justified by an increased risk of thromboembolic complications after replacement of any valve with a mechanical prosthesis.1,2 Most heart valve defects are acquired later in life and are due to degenerative heart valve disease. Heart valve replacement becomes necessary when hereditary or acquired defects severely limit valve function.

心臟瓣膜疾病的主要原因： 3
Main causes of heart valve disease:3

  • 先天性心臟病
    Congenital heart disease
  • 风湿热  Rheumatic fever 
  • 心肌病  Cardiomyopathy
  • 由于心脏病发作导致的心肌损伤
    Heart muscle damage due to heart attack
  • 老化  Aging
  • 先前感染過心內膜炎
    A previous infection with endocarditis 

獲得性瓣膜狹窄可能是瓣膜組織有機變化的結果；瓣膜功能不全可能是心室容量負荷或充血性心力衰竭的次要結果。

Acquired valvular stenosis may be a consequence of organic changes to the tissue of the valve; insufficiency may be a secondary consequence of ventricle volume load or congestive heart failure.

今天，心臟瓣膜手術和/或介入治療的指徵被認為更早。在歐洲，約 25%的心臟手術是進行矯正性心臟瓣膜手術：機械心臟瓣膜特別耐用，但要求患者終身服用口服抗凝藥物。生物心臟瓣膜假體的好處是不需要長期抗凝，但會較早鈣化，並且需要在 10 到 15 年後更換，這樣會增加第二次瓣膜更換手術的風險。

Today, the indication for operation and/or interventional treatment of the heart valves is considered earlier.4 In Europe, corrective heart valve surgery is performed in approximately 25% of all heart operations: Mechanical heart valves are particularly long-lived, but require that the patient takes life-long oral anticoagulation medication.2 Biological heart valve prostheses have the benefit of not requiring prolonged anticoagulation, but calcify sooner and have to be replaced after 10 to 15 years,5 with an increased risk linked to the second valve replacement surgery.

抗凝治療 Anticoagulation

建議所有機械瓣膜患者終身使用口服抗凝治療，使用維生素 K 拮抗劑（VKA）。 6

Lifelong oral anticoagulation treatment using a VKA is recommended for all patients with a mechanical valve.6

根據美國胸科醫學會（ACCP）的指導方針，對於患者建議如下： 7
According to the American College of Chest Physicians (ACCP) guidelines, the following is recommended for patients:7

  • 對於有機械主動脈瓣的患者，VKA 治療的目標 INR 為 2.5（範圍 2.0-3.0），優於較低的目標（2C 級建議）
    In patients with a mechanical aortic valve, VKA therapy with a target INR of 2.5 (range 2.0-3.0) over lower targets (Grade 2C recommendation)
  • 對於有機械主動脈瓣的患者，VKA 治療的目標 INR 為 2.5（範圍 2.0-3.0），優於較高的目標（1B 級建議）
    In patients with a mechanical aortic valve, VKA therapy with a target INR of 2.5 (range 2.0-3.0) over higher targets (Grade 1B recommendation)
  • 在有機械二尖瓣的患者中，VKA 治療的目標為 3.0（範圍 2.5-3.5），優於較低的 INR 目標（2C 級建議）
    In patients with a mechanical mitral valve, VKA therapy with a target of 3.0 (range 2.5-3.5) over lower INR targets (Grade 2C recommendation)
  • 在同時有機械心臟瓣膜的患者中，無論是主動脈瓣還是二尖瓣，目標 INR 為 3.0（範圍 2.5-3.5），優於目標 INR 2.5（範圍 2.0-3.0）（2C 級建議）
    In patients with mechanical heart valves in both the aortic and mitral position, target INR 3.0 (range 2.5-3.5) over target INR 2.5 (range 2.0-3.0) (Grade 2C recommendation)

美國心臟病學會（ACC）/美國心臟協會（AHA） 8 對抗凝治療的使用提供了相似的建議。然而，目標 INR 應根據患者的風險因素和假體的血栓形成性進行調整。 6

The American College of Cardiology (ACC)/American Heart Association (AHA)8 provide fairly similar recommendations regarding the use of anticoagulation. However, the target INR should be adapted to patient risk factors and the thrombogenicity of the prothesis.6

透過個別調整抗凝劑強度、患者參與以及使用國際標準化比率（INR）作為控制參數，可以改善術後死亡率和併發症。研究如 ESCAT（早期自我控制抗凝試驗） 9,10 顯示，在患者進行自我管理的情況下，他們能夠在最佳治療目標範圍內保持更高的時間百分比，從而顯著降低併發症的發生率。歐洲心臟病學會（ESC）和歐洲心胸外科協會（EACTS）最近的指導方針也強烈支持 INR 自我管理，前提是進行適當的培訓和質量控制（I 類，B 級建議） 6

Post-operative mortality and morbidity can be improved through individual adjustment of anticoagulation intensity, involvement of the patient, and the use of the international normalized ratio (INR) as a control parameter. Studies such as ESCAT (Early Self Controlled Anticoagulation Trial)9,10 have shown that in cases where patients practice self-management they remain within their optimum therapeutic target range for a higher percentage of time and so significantly reduce the rate of complications. Recent guidelines from the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) also strongly support INR self-management provided appropriate training and quality control are performed (class I, level B recommendation)6

非維生素 K 拮抗劑口服抗凝治療在有機械心臟瓣膜的患者中是禁忌的。 11

Non-vitamin K antagonist oral anticoagulant (NOAC) treatment is contraindicated in patients with a mechanical heart valve.11

風險因素： Risk factors:

心房顫動、以往血栓栓塞、左心室功能不全、促凝狀況、舊型血栓生成瓣膜、機械三尖瓣或多於 1 個機械瓣膜。 8

trial fibrillation, previous thromboembolism, left ventricular dysfunction, hypercoagulable conditions, older-generation thrombogenic valves, mechanical tricuspid valves, or more than 1 mechanical valve.8

心房顫動 Atrial fibrillation

心房顫動（AF）是人們最常見的心律不整。在 AF 中，心臟的兩個上腔（心房）以混亂和不規則的方式跳動。這種情況會導致血流不暢和心臟內血塊的形成，這些血塊可能隨後釋放到大腦的動脈中，導致中風。這主要是老年人的問題。

Atrial fibrillation (AF) is the most common heart rhythm abnormality that people develop. During AF the heart’s two upper chambers (the atria) beat chaotically and irregularly. The condition causes poor blood flow and the development of blood clots within the heart which can subsequently release into the arteries of the brain and cause a stroke. It is primarily a problem of the elderly.

AF 通常被分類如下：
AF is often classified as follows:

  • 反覆性 AF：兩次或更多次的 AF 發作
    Recurrent AF: two or more episodes of AF

  • 發作性心房顫動：發作在七天內自動結束
    Paroxysmal AF: episodes end spontaneously within seven days

  • 持續性心房顫動：需要藥物或電擊轉復來終止心律失常
    Persistent AF: pharmacologic or electrical cardio-version is required to terminate the arrhythmia

  • 永久性心房顫動：儘管接受治療以結束心律失常，仍持續存在心房顫動，或當電擊轉復不適合時
    Permanent AF: sustained AF despite treatment to end the arrhythmia or when cardio version is inappropriate

大約 15%-20%的缺血性中風發生在有心房顫動的患者中。 12 在心房顫動患者中，中風的歸因風險隨著年齡顯著增加，從 50-59 歲的 1.5%上升到 80-89 歲的 23.5%。 13 事實上，年長的心房顫動患者中風風險最高，出血風險也最高。 14 在調整合併心血管疾病後，心房顫動與死亡風險增加 50%至 90%相關。 15 此外，中風是導致嚴重長期殘疾的主要原因。 16

Approximately 15%-20% of ischemic strokes occur in patients with AF.12 The attributable risk of stroke in AF patients increases significantly with age, rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years.13 Indeed, elderly patients with AF are at the highest risk for stroke and the highest risk for hemorrhage.14 After adjusting for comorbid cardiovascular conditions, AF is associated with a 50% to 90% increase in mortality risk.15 Furthermore, stroke is a leading cause of serious long-term disability.16

心房顫動是全球最常見的心律不整，根據 2010 年的估計，全球年齡調整後的患病率為 0.5%——近 3350 萬人。在過去 20 年中，由於心房顫動的住院人數增加了 66%，而且新興證據也顯示心房顫動與肺栓塞之間存在關聯。

AF is the most common arrhythmia worldwide and the estimated global age adjusted prevalence was 0.5% in 2010 – nearly 33.5 million individuals.17 During the last 20 years there has been a 66% increase in hospitalizations due to AF and emerging evidence has also indicated an association between AF and pulmonary embolism.18

抗凝療法  Anticoagulation

五項具有里程碑意義的臨床試驗——AFASAK、SPAF、BAATAF、CAFA 和 SPINAF——已經證明了口服抗凝劑華法林在預防心房顫動患者中中風的明確好處。

Five landmark clinical trials – AFASAK, SPAF, BAATAF, CAFA, and SPINAF – have demonstrated the unequivocal benefits of the VKA, warfarin, in preventing stroke among patients with AF.19-23 

最近 BAFTA 研究確認了這一點，該研究顯示與阿司匹林相比，華法林治療可顯著降低老年人中風風險 64%。重大出血的風險降低了 12%（雖然不具顯著性）。

This was confirmed recently by the BAFTA study that showed stroke risk is significantly lowered by 64% with warfarin treatment compared to aspirin in an elderly population. The risk for major hemorrhage was reduced by 12% (although non-significant).24

在口服抗凝治療指示的情況下，應進行風險分層（例如使用 CHA2DS2-VASc 評分）以估計非瓣膜性心房顫動患者中中風的風險。 25 CHA2DS2-VASc 評分系統根據患者的年齡和性別以及以下中風風險因素分配分數： 26

Where oral anticoagulation is indicated, a risk stratification (e.g. using the CHA2DS2-VASc score) should be performed to estimate the risk of stroke in patients with nonvalvular AF.25 The CHA2DS2-VASc scoring system assigns a score based on the age and sex of a patient as well as the following risk factors for stroke:26

  • 充血性心力衰竭病史
    Congestive Heart Failure history

  • 高血壓病史  Hypertension history

  • 中風/短暫性缺血發作（TIA）/血栓栓塞病史
    Stroke/transient ischemic attack (TIA)/thromboembolism history

  • 血管疾病病史
    Vascular disease history

  • 糖尿病病史
    Diabetes mellitus history

最近的歐洲心臟病學會指導方針強烈建議（I 類 – A 級）使用 CHA2DS2-VASc 評分來預測心房顫動患者的中風風險。 27 一般來說，沒有臨床中風風險因素的患者不需要抗血栓治療，而有中風風險因素的患者（即男性 CHA2DS2-VASc 評分為 1 或以上，女性為 2 或以上）可能會從口服抗凝劑治療中受益。 27

Recent ESC guidelines highly recommend (class I – level A) the CHA2DS2-VASc score for stroke risk prediction in AF patients.27 In general, patients without clinical stroke risk factors do not need antithrombotic therapy, while patients with stroke risk factors (i.e. CHA2DS2-VASc score of 1 or more for men, and 2 or more for women) are likely to benefit from oral anticoagulant therapy.27

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