|
Sum of points according to the CHA2DS2VASc scale | ||
|
One “major” risk factor or ≥ 2 “clinically significant minor risk factors” |
Oral anticoagulants |
|
|
One "clinically significant small risk factor" |
Oral anticoagulants or acetylsalicylic acid at a dose of 75 – 325 mg/day. Oral coagulants have an advantage over acetylsalicylic acid. |
|
|
No risk factors |
Acetylsalicylic acid or do not use antithrombotic agents. It is preferable not to use antithrombotic agents. |
Antiplatelet drugs, including acetylsalicylic acid, are also widely applicable, and if there are indications for the use of acetylsalicylic acid, it is advisable to use it at a dose of 75–325 mg/day. It has been proven that in smaller doses the antithrombotic effect is not achieved, and in larger doses the risk of bleeding increases.
The risk of bleeding complications should also be assessed (Table 4).
Index value HAS- BLED≥ 3 indicates a high risk of bleeding. In this case, the dose of the antithrombotic drug should be carefully selected, and the risk of bleeding during treatment with vitamin K antagonists and acetylsalicylic acid is comparable.
Table 4
Has-bleeding risk scale
|
Clinical characteristics |
Number of points (minimum 9) |
|
|
Arterial hypertension (systolic blood pressure >160 mmHg) | ||
|
Impaired renal function (dialysis, transplantation or serum creatinine > 200 µmol/l); liver (for example, cirrhosis or a more than twofold increase in bilirubin, combined with a threefold increase in AST, ALT, or alkaline phosphatase. | ||
|
Bleeding (history, or predisposition, hemorrhagic diathesis, anemia, etc.) | ||
|
Labile INR (unstable, high, or recently reached target INR) | ||
|
Age over 65 years | ||
|
Taking certain medications or alcohol (1 point each) (antiplatelet drugs, NSAIDs, alcohol abuse) |
Prevention of thromboembolic complications during cardioversion
The increased risk of thromboembolism after cardioversion is well known. In this regard, anticoagulation is considered mandatory before elective cardioversion if AF persists for more than 48 hours or its duration is unknown (Fig. 3).
Treatment with vitamin K antagonists (INR 2.0–3.0) should be continued for at least 3 weeks before cardioversion. Thromboprophylaxis is recommended before electrical or drug cardioversion in patients with AF duration >48 hours. Vitamin K antagonist therapy should be continued for at least 4 weeks after cardioversion, given the risk of thromboembolism associated with dysfunction of the left atrium and its appendage (so-called “atrial stunning” ≫). In the presence of risk factors for stroke or recurrent AF, treatment with vitamin K antagonists is carried out lifelong, even if sinus rhythm is maintained after cardioversion.
If an episode of AF lasts less than 48 hours, cardioversion can be performed urgently under cover of intravenous unfractionated heparin (followed by infusion or subcutaneous administration of low molecular weight heparin).
In patients with risk factors for stroke, treatment with oral anticoagulants is started after cardioversion and continued for life. Unfractionated or low molecular weight heparin is used until the target INR (2.0-3.0) is achieved. In the absence of risk factors for thromboembolism, oral anticoagulants should not be prescribed.
Patients with AF >48 hours and haemodynamic compromise (angina, myocardial infarction, shock or pulmonary edema) should undergo urgent cardioversion. Before restoring the rhythm, unfractionated (UFH) or low molecular weight (LMWH) heparin is prescribed. After cardioversion, oral anticoagulants are prescribed, and heparin treatment is continued until the target INR (2.0-3.0) is achieved. The duration of anticoagulant therapy (4 weeks or lifelong) depends on the presence of stroke risk factors.
The mandatory 3-week anticoagulation before cardioversion may be reduced if transesophageal echocardiography does not reveal thrombus in the left atrium or left atrial appendage. Using this method, it is possible to detect not only a thrombus in the left atrial appendage or in other parts of this chamber of the heart, but also spontaneous echoes or
plaque in the aorta. Transesophageal echocardiography-guided cardioversion may serve as an alternative to 3 weeks of anticoagulation before restoring rhythm when experienced personnel and technical capabilities are available, and when early cardioversion is necessary, anticoagulation is not possible (patient refusal or high risk of bleeding), or there is a high likelihood of thrombus in the left the atrium or its appendage. If transesophageal echocardiography does not reveal a thrombus in the left atrium, then UFH or LMWH is prescribed before cardioversion, the administration of which is continued until the target INR is achieved while taking oral anticoagulants.
If a thrombus is present in the left atrium or left atrial appendage, treat with a vitamin K antagonist (INR 2.0–3.0) and repeat transesophageal echocardiography. When the thrombus dissolves, cardioversion can be performed, after which lifelong therapy with oral anticoagulants is prescribed. If thrombus persists, rhythm restoration may be abandoned in favor of ventricular rate control, especially if AF symptoms are controlled given the high risk of thromboembolism with cardioversion.
With an INR of more than 3.5, the risk of bleeding, including intracranial, increases significantly, and with an INR of 2.0-3.0, the risk of bleeding is not higher than with less than 2.0, but there is a therapeutic effect.
To assess the risk of bleeding, bleeding risk scales have been developed for patients receiving anticoagulant therapy. The most famous and effective in practice is the HAS-BLED (IIa A) scale. A value of 3 or more means a high risk of bleeding and requires vigilance - IIa B, but this does not exclude the use of oral anticoagulants.
HAS-BLED bleeding risk scale:
When taking oral anticoagulants and vitamin K antagonists, the INR serves as a guide to the clinical effect. For the prevention of thromboembolic complications in AF without heart valve lesions, the therapeutic range of INR is 2.0-3.0 (the optimal range between effectiveness and safety; ideally 2.2-2.3). Maintaining the INR within 1.5-2.5 in elderly patients did not pay off (the number of strokes increased), therefore, maintaining the INR less than 2.0 is not recommended. With INR>3.5, the risk of bleeding, primarily intracranial, increases significantly.
Sensitivity to warfarin is determined by carriage of the cytochrome P450 2C9 gene (CYP2C9), which controls the metabolism of warfarin in the liver, and the vitamin K epoxide reductase complex gene (VKORC1). They determine the required dose of warfarin and the risk of bleeding. Genotyping of these genes is justified only in patients with a high risk of bleeding. In 2010, the FDA published warfarin maintenance dose levels based on the polymorphisms of the above genes.
Separate groups of patients:
- planned surgical interventions: If the risk of thromboembolic complications is not high and there are no mechanoprosthetic heart valves, temporary withdrawal of vitamin K antagonists with the creation of subtherapeutic anticoagulation (INR) is possible<1,5) на срок до 48 часов без перехода на гепарин – IIa C. При приеме варфарина обычно отменяют за 5 дней до операции. В случае же высокого риска тромбэмболических осложнений или наличия механопротезов клапанов сердца временная отмена пероральных антикоагулянтов рекомендована с переходом на терапевтические дозы гепарина или НМГ («терапия моста») – IIa C. После вмешательства возобновление приема антагониста витамина К (в прежней дозе) возможно вечером дня операции при условии полного и успешного гемостаза – IIa B. При этом в случае «терапии моста» на этапе возобновления приема антагониста витамина К время перекреста с гепарином или НМГ должно быть не менее 5 суток. Если операция проводится экстренно, то можно, при необходимости дать небольшие дозы витамина К.
- ACVA or TIA: before starting antithrombotic therapy, it is necessary to make sure that blood pressure is controlled and to exclude cerebral hemorrhage using CT or MRI - IIa C. In the absence of intracranial bleeding, the issue of prescribing oral anticoagulants can be decided no earlier than 2 weeks after stroke, and in the presence of intracranial bleeding bleeding, anticoagulants should not be prescribed - IIa C. If the focus of ischemic stroke is large, it is advisable to postpone the prescription of anticoagulants due to the risk of hemorrhagic transformation of the focus - IIa C. If a patient with AF develops a TIA, but stroke is excluded and there is no risk of bleeding, then it is recommended as it is possible to initiate the use of anticoagulants earlier - IIa C. In case of hemorrhagic stroke, anticoagulants are discontinued immediately and re-prescribed after a long period of time and in the absence of a high risk of recurrent hemorrhagic stroke.
- Chronic ischemic heart disease: In case of a stable course of IHD (there is no acute ischemia and no TBKA is planned), monotherapy with oral anticoagulants, primarily warfarin, can be used (it is at least as effective as aspirin in the secondary prevention of IHD, but there is less risk of bleeding than when taking acetylsalicylic acid and clopidogrel; studies ASPECT-2, WARIS-2) – IIb C. After surgical revascularization of the myocardium in a patient with AF, the issue of combining vitamin K antagonists with one of the antiplatelet agents can be considered, but this is poorly studied – IIb C.
- PCI: It is necessary to avoid, if possible, implantation of drug-eluting stents, since in this case it will be necessary to take triple antithrombotic therapy for at least 1 year, and try to install bare metal stents. In this case, triple antiplatelet therapy is required for 1 month, then vitamin K antagonist + clopidogrel for a year - IIa C. In case of implantation of drug-eluting stents, triple antiplatelet therapy is required for 3-6 months, then vitamin K antagonist + clopidogrel until years after stenting - IIa C. If the patient is planning TBKA and has a high or moderate risk of thromboembolism, then INR values should be left within 2.0-3.0, but choose, if possible, radial access - IIa C. For primary emergency TBKA and INR more than 2.0, it is better to abstain from taking IIb/IIIa receptor blockers. Triple or dual antithrombotic therapy should be carried out in combination with proton pump inhibitors or H2-histamine receptor inhibitors and maintain the INR within the range of 2.0-2.5 - IIb C.
- OKS: in case of ACS and PCI, triple antiplatelet therapy is required for at least 6 months, then a vitamin K antagonist + clopidogrel or acetylsalicylic acid until a year after stenting - IIa C. In case of ACS without PCI, either a combination of a vitamin K antagonist is recommended for a year (INR 2, 0-3.0) with acetylsalicylic acid or monotherapy with a vitamin K antagonist with an INR of 2.5-3.5 – IIa C. Approaches to the treatment of ACS during initial therapy with new oral anticoagulants have not been studied, so in this case it is recommended to switch to warfarin. ECV for unstable hemodynamics, inability to control heart rate or persistent ischemia; preferably intravenous administration of beta-blockers (I C) or non-dihydropyridine ACs (IIa C; in the absence of clinical signs of HF); in the presence of severe CHF, digoxin (IIb C) and/or amiodarone (I C) can be used.
- elderly: with age, in terms of preventing thromboembolic complications, the effectiveness of antiplatelet agents decreases, but the effectiveness of oral anticoagulants remains; but in the elderly, the risk of stroke and other thromboembolism gradually increases, despite continued use of anticoagulants.
- valve defects: for a combination of atrioventricular valve defects, only oral anticoagulants; If there is a mitral valve defect, its correction should be separately considered. The target INR values for a mechanical prosthetic mitral valve are at least 2.5, for the aortic valve – 2.0 (I B).
- pregnancy: ECV is possible in all trimesters (same power charges) – I C; in the first trimester, try to avoid any medications; beta blockers are best avoided (fetal growth restriction); in terms of anticoagulant therapy: only with a high risk of TE, in the first trimester only heparin or LMWH, VKA only from the 2nd trimester (I C) and canceled a month before birth (I B); to reduce heart rate, beta blockers and AK (very carefully in the first trimester) – IIa C; in terms of restoring rhythm, you can use flecainamide or ibutilide – IIb C; if beta blockers and AKs are contraindicated, digoxin – IIb C can be used.
- postoperative AF: 30% after CABG, 40% after valve surgery and 50% after combined heart surgery develop AF; effective prevention - beta blockers and amiodarone, also, but less effectively reduce the risk of sotalol and atrial pacing; ACE inhibitors and ARBs, as well as corticosteroids, statins are controversial, sometimes even harmful.
- CHF: to control heart rate, first of all, beta blockers - I A. If they are insufficiently effective, digoxin - I B. Non-dihydropyridine ACs only with preserved EF and with ineffectiveness of beta blockers - IIb C. In case of unstable hemodynamics and low EF, it is recommended to start treatment with amiodarone – I B; in the absence of DPP, the alternative in such cases is digoxin - I C. If there are indications for CRT, consider ablation of the AV node - IIa B. In severe CHF and unstable hemodynamics, only amiodarone is used to control the rhythm - I C. It is possible to consider performing RFA – IIb B.
- DPP: in the presence of a combination of symptomatic DPP and AF, RFA is indicated - I A; in socially responsible professions, even with non-symptomatic DPP and AF - I B. In asymptomatic, but clearly manifest forms of DPP and AF, RFA can also be considered (recommended for additional examination of TEES) - I B. In the absence of obvious indications against the background of a combination of DPP and AF, RFA may be carried out after an explanatory conversation about possible risks at the request of the patient – IIa B.
Shows better results than standard bleeding risk scores that are based only on clinical risk factors. As is known, the benefit of using oral anticoagulants (OAC) for AF is based on a balance between reducing the risk of ischemic stroke and increasing the risk of major bleeding. Currently, the most commonly used scale to assess the risk of bleeding during OAC is HAS-BLED, which takes into account clinical risk factors. However, in recent years there has been evidence that some biomarkers can provide additional information about the risk of bleeding in patients with AF, so it would be reasonable to assume that our ability to predict these complications will improve if these variables are also included in the model. The new scale for assessing the risk of bleeding is called ABC (from the English words “age”, “biomarkers” and clinical history). It has demonstrated higher sensitivity and feasibility than the popular clinical scores HAS-BLED and ORBIT, so it has good prospects as a tool to inform clinical decisions in the field of anticoagulation in patients with AF. The study on this new scale was published in the June 4, 2016 issue of the Lancet.
This study was conducted by a team of scientists from Uppsala University in Sweden with financial support from Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim and Roche Diagnostics. The scientists included in the new model those available biomarkers that seemed to them to have the highest predictive value in assessing the risk of bleeding in AF. These included growth differentiation factor-15 (GDF-15), which is a marker of oxidative stress; troponin T, determined by highly sensitive assay methods (hs-TnT), which is a marker of myocardial damage; cystatin C or estimated glomerular filtration rate (eGFR) used to assess kidney function, as well as markers of anemia (hemoglobin or hematocrit). The model also included clinical risk factors and levels of the N-terminal fragment of brain natriuretic peptide type B precursor (NT-proBNP), which has been used as a biomarker of stroke risk.
The new risk score was first validated in a large cohort of patients who participated in the ARISTOLE trial (Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation), in which patients received either apixaban (Eliquis, manufactured by Bristol-Myers Squibb/Pfizer) or warfarin. Biomarker data were available for a total of 14,537 ARISTOLE participants. Major bleeding occurred in 662 people.
Additional Information: Even short-term administration of NSAIDs to patients with atrial fibrillation on anticoagulants increases the risk of bleeding
Using the new ABC Bleeding Risk Score, the researchers found that the strongest predictors of major bleeding in ARISTOLE participants were GDF-15, hemoglobin, hs-TnT, age, and a history of previous bleeding. These five variables were included in a new, revised version of the ABC model, whose ability to predict the risk of major bleeding was compared with that of the HAS-BLED score and the newer ORBIT score. The so-called c-index was 0.68 for the ABC scale (a value of 1.0 corresponds to ideal model resolution, and a value of 0.5 is considered poor and approximately corresponds to the predictive value of a coin toss). The HAS-BLED scale had a c-index of 0.61, and the ORBIT scale had a c-index of 0.65. The differences between both these scales and the ABC scale were significant: P<0,001 для шкалы HAS-BLED и P=0,0008 для шкалы ORBIT. Шкала ABC демонстрировала равные результаты у пациентов, которые получали в рамках исследования апиксабан или варфарин, и никаких значимых взаимодействий с эффектами тестировавшихся препаратов обнаружить не удалось.
The researchers then moved on to externally validate their results using biomarker data from the RE-LY trial (Randomized Evaluation of Long-term Anticoagulation Therapy), in which patients with AF received either dabigatran (Pradaxa, manufacturer Boehringer Ingelheim) or warfarin. Archival blood samples for biomarker testing were available for 8468 patients, with 463 major bleeding events occurring during the study. In the RE-LY study population, the new ABC scale also demonstrated a higher c-index value than its two competing scales: ABC had a c-index of 0.71, HAS-BLED had a c-index of 0.62, and ORBIT had a c-index of 0.71. 0.68 (differences were highly significant: P<0,0001 и P=0,0016, соответственно). Шкала ABC также превосходила шкалы HAS-BLED и ORBIT с точки зрения способности прогнозировать внутричерепные кровоизлияния: значения c-индекса для трех шкал составили 0,66, 0,58 и 0,60, соответственно). Внешняя валидизация является важным шагом при подтверждении ценности новых шкал, и, таким образом, шкала ABC успешно справилась с этим этапом, превзойдя конкурентные шкалы.
It is also noteworthy that the new score also assessed bleeding risk equally well in different subgroups of patients with AF and was even able to predict risk quite accurately in patients with low HAS-BLED and ORBIT scores.
Answering the question about the availability of the new scale for real practical use, the authors of the work reported that highly sensitive methods for determining troponin are already available in many countries around the world, and in June 2016. Roche plans to market a kit for determining a new biomarker, GDF-15. As for the complexity of the calculations, the authors do not consider this a significant problem: doctors are already actively using nomograms, electronic calculators or mobile applications to determine such commonly used parameters as, for example, creatinine clearance or the GRACE score, so, given the practical value of the scale ABC, most likely, similar auxiliary tools will quickly appear for it too.
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HAS-BLED scale
The HAS-BLED score is a simple and reliable clinical tool for assessing the 1-year risk of major bleeding. Major bleeding is defined as: any intracranial hemorrhage, bleeding requiring hospitalization, or accompanied by a decrease in hemoglobin > 2 g/l, or requiring blood transfusion.
The scale was created based on a real-life cohort of 3978 patients with atrial fibrillation.
The bleeding risk score was introduced by R. Pister et al in 2010 and was named HAS-BLED as an acronym:
— Hypertension - hypertension (systolic blood pressure > 160 mmHg);
— Abnormal renal/liver function - impaired renal function— 1 point (chronic dialysis, or serum creatinine > 200 µmol/L, or history of kidney transplantation) and/orliver dysfunction— 1 point (chronic liver disease or functional impairment: bilirubin > 2× upper limit of normal, or elevated aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase > 3× upper limit of normal);
— Stroke - stroke;
— Bleeding history or predisposition - history of bleeding and/or predisposition to it (eg, bleeding diathesis, anemia);
— Labile international normalized ratio (INR)- labile international normalized ratio< 60 % (an indicator of the blood coagulation system, calculated when determining prothrombin time, the indicator was introduced for uniformity in assessing the effect of anticoagulants on prothrombin time and correcting the prescription of anticoagulant doses);
— Elderly - age (>65 years);
— Drugs/alcohol concomitantly - taking medications together (eg, anticoagulants and non-steroidal anti-inflammatory drugs)— 1 point and/or alcohol— 1 point.
1 point is assigned for each item, the result is a simple sum of points. The maximum number of points on the scale is 9.
The effectiveness of any antithrombotic treatment must be balanced against the risk of major bleeding, especially intracerebral bleeding, which is often fatal. Therefore, the risk of bleeding should be assessed before prescribing anticoagulants in patients with atrial fibrillation.
Patients at high risk of bleeding (HAS-BLED score > 3) should undergo regular clinical evaluation after initiation of oral anticoagulant therapy.
The HAS-BLED score has been included in European and Canadian guidelines for the treatment of atrial fibrillation since 2010. The scale has been validated in various independent cohorts and correlates well with the risk of intracerebral hemorrhage.
Bibliography
1. Pisters R., Lane D.A., Nieuwlaat R., de Vos C.B., Crijns H.J., Lip G.Y. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey // Chest. — 2010 Nov. - 138(5). - 1093-100.
2. Authors/Task Force Members, Camm A.J., Lip G.Y., De Caterina R. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association // Eur. Heart J. - 2012 Nov. - 33(21). - 2719-47.
3. Lip G.Y., Frison L., Halperin J.L., Lane D.A. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score / / J. Am. Coll. Cardiol. — 2011 Jan 11. — 57(2). - 173-80.
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