VAI TRÒ THUỐC CHỐNG ĐÔNG ĐƯỜNG UỐNG MỚI TRONG PHÒNG NGỪA ĐỘT QUỴ Ở BỆNH NHÂN RUNG NHĨ KHÔNG DO BỆNH VAN TIM

Ts.Bs Đinh Hiếu Nhân Đại Học Y Dược TpHCM VAI TRỊ THUỐC CHỐNG ĐƠNG ĐƯỜNG UỐNG MỚI TRONG PHỊNG NGỪA ĐỘT QUỴ Ở BỆNH NHÂN RUNG NHĨ KHÔNG DO BỆNH VAN TIM I TỔNG QUAN Definitions of AF: A Simplified Scheme Term Definition Paroxysmal AF   AF that terminates spontaneously or with intervention within d of onset Episodes may recur with variable frequency Persistent AF  Continuous AF that is sustained >7 d Long-standing persistent AF  Continuous AF >12 mo in duration Permanent AF  The term “permanent AF” is used when the patient and clinician make a joint decision to stop further attempts to restore and/or maintain sinus rhythm Acceptance of AF represents a therapeutic attitude on the part of the patient and clinician rather than an inherent pathophysiological attribute of AF Acceptance of AF may change as symptoms, efficacy of therapeutic interventions, and patient and clinician preferences evolve   Nonvalvular AF  AF indicates atrial fibrillation AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair Atrial fibrillation  AF is the most common heart rhythm disturbance1  It is estimated that in individuals aged 40 years will develop AF1  In 2007, 6.3 million people in the US, Japan, Germany, Italy, Spain, France, and UK were living with diagnosed AF2  Owing to the aging population, this number is expected to double within 30 years3 Lloyd-Jones DM et al Circulation 2004;110:1042-1046 Decision Resources Atrial Fibrillation Report Dec 2008 Go AS et al JAMA 2001;285:2370-2375 Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg Rationale for Stroke Prevention in AF      AF is associated with a 25% life-time risk of stroke1 Cardio-embolic stroke has a 30-day mortality of 25% and a year mortality of almost 50%2 Cardio-embolic strokes are more severe and more often disabling than strokes of other etiology Once a stroke has happened the risk for subsequent cardio-embolic stroke is increased 2-3fold AF-related stroke has a 1-year mortality of ~50%3 Wolf PA et al Stroke 1991;22:983-988 Lin H-J et al Stroke 1996; 27:1760-1764 Marini C et al Stroke 2005;36:1115-1119 Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg Anticoagulation in AF: Stroke Risk Reduction  In the past, the most widely used medications for stroke prevention in patients with AF were vitamin K-antagonists (VKAs) and aspirin  VKAs are very effective in preventing stroke among AF- patients • Almost 70% relative risk reduction vs placebo Kirchhof P et al Working Group Report, 2009 Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg Stroke Risk Reduction in AF (Warfarin vs placebo) AFASAK: Peterson et al 811 Lancet 1989;1:175 BAATAF: Investigators 922 NEJM 1990;323;1505 CAFA: Connolly et al, 478 JACC 1991;18:349 SPAF: Investigators 508 Stroke 1990;21:538 SPINAF: Ezekowitz et al 972 NEJM 1992;327:1406 3691 COMBINED 100% 50% Warfarin better 0% –50% –100% Warfarin worse Seniorprofessur Neurologie UniversitätsKlinikum und Universität Heidelberg Arch Intern Med 1994;154:1449-1457 Risk-Based Antithrombotic Therapy Recommendations For patients with nonvalvular AF with prior stroke, transient ischemic attack, or a CHA2DS2-VASc score of or greater, oral anticoagulants are recommended Options include: • warfarin (INR 2.0 TO 3.0), or • dabigatran, or • rivaroxaban, or • apixaban Among patients treated with warfarin, the INR should be determined at least weekly during initiation of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended Re-evaluation of the need for and choice of antithrombotic therapy at periodic intervals is recommended to reassess stroke and bleeding risks COR LOE I I I I A B B B I A I C I C Secondary stroke prevention Recommendations In AF patients who suffer a stroke, aspirin should be considered for prevention of secondary stroke until the initiation or resumption of oral anticoagulation Systemic thrombolysis with rtPA is not recommended if the INR is above 1.7 (or, for patients on dabigatran, if aPTT is outside normal range) NOACs are recommended in preference to VKAs or aspirin in AF patients with a previous stroke After TIA or stroke, combination therapy of OAC and an antiplatelet is not recommended After intracranial haemorrhage, oral anticoagulation in patients with AF may be reinitiated after 4–8 weeks provided the cause of bleeding or the relevant risk factor has been treated or controlled European Heart Journal - doi:10.1093/eurheartj/ehw 210 Class Level IIa B III (harm) C I B III (harm) B IIb B Initiation or resumption of anticoagulation depends on severity of stroke* Time to re-initiation depends on infarct size: – – – 12 day rule TIA Mild stroke Moderate stroke Severe stroke As soon as imaging has excluded a cerebral haemorrhage 3–5 days after symptom onset 5–7 days after stroke onset weeks after stroke onset 12 Day *Mild = NIHSS score 16 NIHSS, National Institutes of Health Stroke Scale Personal communication, Hans-Christoph Diener, 2015 IV SỬ DỤNG VÀ ĐIỀU TRỊ BIẾN CHỨNG XUẤT HUYẾT Dose Selection of Oral Anticoagulant Options for Patients With Nonvalvular AF and CKD (Based on Prescribing Information for the United States)* Renal Function Warfarin Dabigatran† Rivaroxaban† Apixaban† 20 mg QD with the evening meal (CrCl >50 mL/min) 5.0 or 2.5 mg BID‡ Normal/mild impairment Dose adjusted for INR 2.0–3.0 150 mg BID (CrCl >30 mL/min) Moderate impairment Dose adjusted for INR 2.0–3.0 150 mg BID (CrCl >30 mL/min) Severe impairment Dose adjusted for INR 2.0–3.0§ End-stage CKD not on dialysis Dose adjusted for INR 2.0–3.0§ 15 mg QD with the evening meal (CrCl 30–50 mL/min) 75 mg BID║ 15 mg QD with the (CrCl 15–30 evening meal mL/min) (CrCl 15–30 mL/min) Not recommended¶ Not recommended¶ (CrCl