Làm tan huyết khối tĩnh mạch đối với đột quỵ do thiếu máu cục bộ cấp sau cơn nhồi máu cơ tim gần đây

Làm tan huyết khối tĩnh mạch đối với đột quỵ do thiếu máu cục bộ cấp sau cơn nhồi máu cơ tim gần đây Cơ sở và mục đích — Tính an toàn của IV – rtPA (chất kích hoạt plasminogen mô tĩnh mạch) trong điều trị đột quỵ do thiếu máu cục bộ cấp tính (AIS) sau nhồi máu cơ tim (MI) gần đây vẫn còn là vấn đề tranh luận. Chúng tôi đã nghiên cứu sự an toàn của việc cung cấp IV – rtPA cho bệnh nhân AIS bị MI trong vòng 3 tháng trước đó. tháng. Bệnh nhân được chia thành 2 nhóm: được điều trị hoặc không được điều trị với liều IV – rtPA tiêu chuẩn cho AIS. Các biến chứng tim (vỡ / chèn ép tim, thuyên tắc huyết khối trong tim, hoặc loạn nhịp đe dọa tính mạng) được so sánh giữa các nhóm và được đánh giá theo loại NMCT (nhồi máu cơ tim không có đoạn ST chênh lên [STEMI], hoặc STEMI) và thời gian trôi qua giữa các mạch Các sự kiện. Kết quả — Một trăm lẻ hai bệnh nhân đã được bao gồm; 46 (45,1%) được lấy từ tổng quan tài liệu. Tuổi trung bình (khoảng tứ phân vị) là 64 (53–75) tuổi, và 69 (67,6%) là nam giới. Bốn mươi bảy (46,1%) nhận IV – rtPA. Trong nhóm được điều trị, lần lượt 25 bệnh nhân (53,2%) và 23 (48,9%) có AIS, MI và STEMI đồng thời, so với 12 (21,8%; P = 0,002) và 36 (65,5%; P = 0,110) bệnh nhân không được điều trị. Bốn (8,5%) bệnh nhân được điều trị bằng IV – rtPA chết vì vỡ / chèn ép tim liên quan hoặc giả định, tất cả đều có STEMI trong tuần trước đột quỵ. Biến chứng này xảy ra ở 1 (1,8%) bệnh nhân trong nhóm không được điều trị (P = 0,178). Không có sự khác biệt về thuyên tắc huyết khối (1 [2,1%) so với 2 [3,6]; P = 1.000) và loạn nhịp tim đe dọa tính mạng (3 [6,4%) so với 7 [12,7]; P = 0,335). Không có bệnh nhân không mắc bệnh STEMI nào dùng IV – rtPA có biến chứng tim. Kết luận — Ở bệnh nhân AIS và NMCT gần đây hoặc đồng thời, loại MI và thời gian trôi qua giữa 2 sự kiện nên được cân nhắc khi quyết định cung cấp IV – rtPA. Mặc dù các biến cố không phải STEMI gần đây hoặc xảy ra đồng thời có vẻ an toàn, nhưng STEMI trong tuần trước đột quỵ cần được lưu ý ngay. Số lượng thấp các sự kiện và sự thiên lệch về công bố có thể có trong kết luận của chúng tôi

Original Contribution Intravenous Thrombolysis for Acute Ischemic Stroke After Recent Myocardial Infarction Case Series and Systematic Review João Pedro Marto, MD; Linda Azevedo Kauppila, MD; Cláudia Jorge, MD; Sofia Calado, MD; Miguel Viana-Baptista, MD, PhD; Teresa Pinho-e-Melo, MD; Ana Catarina Fonseca, MD, PhD Downloaded from http://ahajournals.org by on August 22, 2019 Background and Purpose—The safety of IV–rtPA (intravenous tissue-type plasminogen activator) for acute ischemic stroke (AIS) treatment after recent myocardial infarction (MI) is still a matter of debate We studied the safety of delivering IV–rtPA to AIS patients with a MI within the preceding months Methods—Retrospective review of consecutive AIS admitted to tertiary university hospitals’ and systematic literature review for AIS patients with history of MI in the previous months Patients were divided into groups: treated or not treated with standard IV–rtPA dose for AIS Cardiac complications (cardiac rupture/tamponade, intracardiac thrombus embolization, or life-threatening arrhythmias) were compared between groups and assessed by type of MI (non–STsegment–elevation myocardial infarction [STEMI], or STEMI) and time elapsed between vascular events Results—One hundred and two patients were included; 46 (45.1%) were derived from literature review Median age (interquartile range) was 64 (53–75) years old, and 69 (67.6%) were men Forty-seven (46.1%) received IV–rtPA In the treated group, 25 (53.2%) and 23 (48.9%) patients had, respectively, concurrent AIS and MI and STEMI, in comparison with 12 (21.8%; P=0.002) and 36 (65.5%; P=0.110) patients in the nontreated Four (8.5%) IV–rtPA–treated patients died from confirmed or presumed cardiac rupture/ tamponade, all with a STEMI in the week preceding stroke This complication occurred in (1.8%) patients in the nontreated group (P=0.178) There were no differences in thrombus embolization (1 [2.1%) versus [3.6]; P=1.000) and life-threatening arrhythmias (3 [6.4%) versus [12.7]; P=0.335) No non-STEMI patients receiving IV–rtPA had cardiac complications Conclusions—In patients with AIS and recent or concurrent MI, MI type and the time elapsed between the events should be taken into consideration when deciding to deliver IV–rtPA Although recent non-STEMI or concurrent events seem safe, STEMI in the week preceding stroke should prompt caution The low number of events and publication bias may have influenced our conclusions.   (Stroke 2019;50:00-00 DOI: 10.1161/STROKEAHA.119.025630.) Key Words: heart ◼ hospital ◼ myocardial infarction ◼ stroke ◼ systematic review ◼ therapeutics ◼ tissue-type plasminogen activator A fter myocardial infarction (MI), there is an increased risk of acute ischemic stroke (AIS).1,2 However, how to manage an AIS after recent MI, namely if IV–rtPA (intravenous tissue-type plasminogen activator) should be performed, is a question that remains to be answered Clinical trials that led to the approval of intravenous alteplase in AIS excluded patients with acute MI or presumed post-MI complications.3–5 The most feared complications of treating these patients with IV– rtPA are myocardial rupture, cardiac tamponade after post-MI pericarditis, and embolization of ventricular thrombus Also, patients with acute MI are usually treated with double antiplatelet treatment and anticoagulants that may increase the risk of hemorrhagic transformation of ischemic brain tissue A survey of stroke clinicians’ practice regarding thrombolysis prescription outside formal inclusion criteria6 disclosed that one-third would consider performing thrombolysis after recent non–ST-segment–elevation myocardial infarction (NSTEMI), whereas only 25% would so after recent ST-segment–elevation myocardial infarction (STEMI) American Heart Association/ American Stroke Association guidelines initially considered recent MI (preceding months) as an absolute contraindication to treatment with IV–rtPA.7 In 2013, recent MI was considered as a relative contraindication,8 and in both 2016 American Heart Association/ American Stroke Association Scientific Statement and 2018 guidelines, IV–rtPA was considered reasonable.9,10 The strength given Received March 17, 2019; final revision received June 30, 2019; accepted July 10, 2019 From the Department of Neurology, Hospital Egas Moniz, Centro Hospitalar Lisboa Ocidental, Portugal (J.P.M., S.C., M.V.-B.); CEDOC – Nova Medical School, Universidade Nova de Lisboa, Portugal (J.P.M., S.C., M.V.-B.); Stroke Unit, Department of Neurology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal (L.A.K., T.P.-e.-M., C.F.); Department of Cardiology, Hospital de Santa Maria, University of Lisboa, Portugal (C.J.); and Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal (T.P.-e.-M., C.F.) The online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.119.025630 Correspondence to Ana Catarina Fonseca, MD, PhD, Serviỗo de Neurologia, Hospital de Santa Maria, Avenida Professor Egas Moniz, 1649-035 Lisboa, Portugal Email acfonseca@medicina.ulisboa.pt © 2019 American Heart Association, Inc Stroke is available at https://www.ahajournals.org/journal/str DOI: 10.1161/STROKEAHA.119.025630 2  Stroke  October 2019 to these latest recommendations depends on MI characteristics and is based on expert’s opinion European Stroke Organization guidelines give no indication on how to manage these patients.11 With only seldom case reports available, evidence supporting or contradicting IV–rtPA treatment in AIS after recent MI is scarce We studied the safety of IV–rtPA in stroke patients with an MI within the preceding months by performing a hospital case series analysis and a systematic literature review Methods Study Design and Patient Selection This article adheres to the American Heart Association Journals’ implementation of the Transparency and Openness Promotion Guidelines Anonymized data supporting the findings of this study will be available on reasonable request We retrospectively reviewed a database of consecutive AIS admitted to tertiary university hospitals’ stroke units (from January 2004 to December 2018 in Centro Hospitalar Lisboa Norte and from January 2010 to December 2018 in Centro Hospitalar Lisboa Ocidental) and performed a systematic literature review searching for AIS patients with a history of MI in the previous months Patients were divided into groups: treated with IV–rtPA (standard dose for AIS - 0.9 mg/kg) and those without IV–rtPA treatment (control group) Patients with MI during or after IV–rtPA treatment were not considered For the purpose of the systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.12 The present study was approved by local ethics committees Downloaded from http://ahajournals.org by on August 22, 2019 Stroke and MI Definition Stroke was defined as a new syndrome of rapidly developing clinical symptoms or signs of focal disturbance of cerebral function, lasting longer than 24 hours and with no apparent cause other than vascular origin, regardless of whether infarction was evident on cerebral imaging.13 MI was considered if there was a rise or fall of cardiac biomarker values (preferably cardiac troponin), with at least value above the 99th percentile upper reference limit, and with at least one of the following: symptoms of ischemia; new or presumed new significant ST-segment–T wave changes or new left bundle branch block; and development of pathological Q waves.14 For STEMI, the following criteria were considered: new ST-elevation at the J point in at least contiguous leads of ≥2.5 mm in men 7 d Hemorrhagic transformation (P1/P2) and sICH according to the ECASS-II classification ECASS-II indicates European Cooperative Acute Stroke StudyII; IV–rtPA, intravenous thrombolysis; NSTEMI, non–ST-segment–elevation myocardial infarction; sICH, symptomatic intracranial hemorrhage; and STEMI, ST-segment–elevation myocardial infarction *One patient with inferior STEMI died after cardiac arrest of unknown cause †Confirmed and fatal in left anterior STEMI One patient with inferior STEMI and presumed wall rupture/ cardiac tamponade after dying from cardiogenic shock One patient with inferior STEMI with nonfatal pericardial effusion ‡One patient with inferior STEMI had both arrhythmia (ventricular fibrillation) and embolization complications §One patient with inferior STEMI had pulseless electrical activity Downloaded from http://ahajournals.org by on August 22, 2019 significant, which can be due to the small number of included patients In addition, higher mean age and a lower frequency of PCI in the IV–rtPA group may have contributed to these results.17,24 The low number of events5 precludes a multivariate logistic regression model adjusting for potential confounders Thrombus embolization events were rare and had a similar frequency in both groups, which seems to be in line with the last American Heart Association/ American Stroke Association guidelines statement that may be reasonable to perform IV–rtPA in patients with stroke and intracardiac thrombus.10 There were no differences between groups regarding the occurrence of arrhythmias The acute stress response triggered by the cerebral ischemic event, natural history of MI, and its location, maybe partially responsible for this complication After MI, patients are given antithrombotic regimens that may increase the risk of hemorrhagic complications after thrombolysis Although therapeutic anticoagulation is a formal contraindication,10 dual antiplatelet therapy has raised concerns.25,26 Recent published data27 and recommendations10 not support withholding thrombolysis due to dual antiplatelet therapy, although regimens with potent P2Y12 inhibitors (prasugrel or ticagrelor) may need further study In our study, the rate of radiological and symptomatic hemorrhagic transformation was lower than reported in the ECASS-II trial,16 and no differences were verified between patients with or without IV–rtPA treatment No patients were pretreated with potent P2Y12 inhibitors previous to IV–rtPA treatment In the era of EVT, patients unqualified for IV–rtPA due to medical complications can receive primary mechanical thrombectomy It has been shown that mechanical thrombectomy has good results in patients with contraindications for IV–rtPA,28,29 but not all patients fulfill criteria for EVT (eg, proximal vessel occlusion), and there is no clear evidence that primary EVT has the same results as bridging therapy.30,31 Nevertheless, in patients with AIS after recent STEMI (not concurrent), and large vessel occlusion, primary mechanical thrombectomy may be considered For patients with concurrent AIS and MI, a combined treatment has been proposed.9,32,33 Because IV–rtPA is the only approved treatment for both vascular events, it can be perceived as the best solution A viable option is to give the established dose of alteplase for stroke and, if indicated, proceed with PCI.9 If PCI is performed, procedural decisions (stenting versus balloon angioplasty or type of stent), as well as antithrombotic regimen, can be tailored in each patient according to the risk of ischemic hemorrhagic transformation In patients fulfilling criteria, EVT and PCI can be combined.32 While deciding to give IV–rtPA for AIS and recent MI, the physician should be aware of clinical signs that may suggest increased probability of cardiac complications (eg, pericardial rub) or consider using urgent transthoracic echocardiography.33 Our study has limitations The low number of included patients limits our ability to perform adjusted analysis and, therefore, our conclusions Also, because all cases of confirmed or suspected cardiac wall rupture or tamponade were derived from the literature search, publication bias, with potential overestimation of these cardiac complications, cannot be excluded Nevertheless, this bias is inherent to a systematic review of case reports The lower frequency of STEMI and nonconcurrent events in the IV–rtPA group may indicate a selection bias, reflecting the higher caution of stroke physician in treating these patients Conclusions In patients with AIS and recent or concurrent MI, type of MI and the time elapsed between the events should be taken in consideration while deciding to deliver IV–rtPA Although recent NSTEMI or concurrent events were not associated with cardiac complications, STEMI in the week preceding stroke should prompt caution The low number of events and publication bias may have influenced our conclusions Disclosures Dr Viana-Baptista reports personal fees from Sanofi-Genzyme Portugal, Daiichi Sankyo, and Boehringer Ingelheim outside the submitted 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Association Stroke Council and Council on Epidemiology and Prevention Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for. .. used: ? ?Myocardial Infarction? ??; “Inferior Wall Myocardial Infarction? ??; “Anterior Wall Myocardial Infarction? ??; ? ?Stroke? ??; ? ?Stroke, Lacunar”; ? ?Infarction, Posterior Cerebral Artery”; “Brain Stem Infarctions”;... received thrombolysis later than weeks after MI, and therefore, there may be a selection bias Myocardium fibrosis and scarring are completed weeks after MI, so the definition of recent MI for thrombolysis