Art of Anticoagulation After Recent Ischemic Stroke
2020; Lippincott Williams & Wilkins; Volume: 51; Issue: 9 Linguagem: Inglês
10.1161/strokeaha.120.030997
ISSN1524-4628
AutoresDavid Seiffge, Martina Goeldlin,
Tópico(s)Antiplatelet Therapy and Cardiovascular Diseases
ResumoHomeStrokeVol. 51, No. 9Art of Anticoagulation After Recent Ischemic Stroke Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBArt of Anticoagulation After Recent Ischemic Stroke David J. Seiffge, MD Martina GoeldlinMD David J. SeiffgeDavid J. Seiffge Correspondence to: David Seiffge, MD, Department of Neurology and Stroke Center, Inselspital, University Hospital, Freiburgstrasse, CH-3010 Bern, Switzerland. Email E-mail Address: [email protected] https://orcid.org/0000-0003-3890-3849 Department of Neurology and Stroke Center, Inselspital, Bern University Hospital and University of Bern, Switzerland. , Martina GoeldlinMartina Goeldlin https://orcid.org/0000-0001-5800-116X Department of Neurology and Stroke Center, Inselspital, Bern University Hospital and University of Bern, Switzerland. Originally published6 Aug 2020https://doi.org/10.1161/STROKEAHA.120.030997Stroke. 2020;51:2618–2619This article is a commentary on the followingAnticoagulation Type and Early Recurrence in Cardioembolic StrokeSee related article, p 2724Atrial fibrillation is a major risk factor for stroke and accounts for roughly 20% of ischemic stroke cases. Although therapy with direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) is well established, the question when and how to start therapy—the art of anticoagulation after a recent stroke—is a huge unmet need in current stroke medicine.1The risk of early recurrent ischemic stroke is high among patients with a recent stroke and atrial fibrillation. Early initiation of anticoagulation is thought to protect patients from further damage due to early recurrence. However, recently infarcted brain tissue is vulnerable and anticoagulation might increase the risk of hemorrhagic transformation leading to increased morbidity and mortality.All recent large randomized controlled trials comparing DOACs and VKA in patients with atrial fibrillation excluded patients with a recent stroke.2 Furthermore, trial populations are only marginally representative for patients with acute stroke treated at stroke units and stroke centers.3 In contrast, the HAEST trial,4 published 20 years ago, enrolled patients with atrial fibrillation early and within 30 hours after recent stroke. They compared aspirin and low molecular weight heparin (LMWH) and found that LMWH increases the risk of intracerebral hemorrhage without reducing the risk of early recurrent stroke. Finally, current guideline recommendations are rather based on expert consensus than on high-quality data.In this issue of Stroke, Yaghi et al5 present data on this important topic, helping to guide clinical decisions. They analyzed data from 1289 consecutive patients with ischemic stroke and atrial fibrillation enrolled in prospective local stroke registries from 8 comprehensive stroke centers in the United States. They addressed 2 different questions: First, they investigated whether bridging (defined as LMWH or heparin before introduction of oral anticoagulants) compared with no bridging (no LMWH/heparin) before starting oral anticoagulation after a recent ischemic stroke is beneficial. They found that bridging was associated with an increased risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01–7.42], P=0.047) but did not reduce the risk of recurrent ischemic stroke. Second, they compared DOAC and VKA-therapy and found that DOAC treatment was associated with a lower rate of recurrent ischemic events within 90 days (5.3% versus 10.0%; hazard ratio, 0.51 [95% CI, 0.29–0.87]; P=0.015) without a significant difference in rate of symptomatic intracranial hemorrhage (1.2% versus 2.0%; hazard ratio, 0.57 [95% CI, 0.22–1.48]; P=0.246). They thus conclude that DOACs without prior bridging therapy seem to have the most favorable risk-benefit-profile in patients with ischemic stroke and AF.The authors should be complimented for running this collaborative, comprehensive study that reflects current practice in specialized centers in the United States. They analyzed a rich dataset and adjusted for many relevant (known) confounders including high-risk cardiac abnormalities (ie, presence of cardiac thrombus). However, unmeasured factors (such as infarct location and poststroke blood pressure control) and bias by indication may have influenced the results. Interestingly, roughly 15% of the patients received bridging therapy before starting any anticoagulation.Their findings have direct clinical implications: (1) bridging with LMWH/heparin should be generally avoided. However, further studies enrolling more patients with high-risk cardiac abnormalities are needed to identify whether particular subgroups might have a benefit from bridging, accounting for the pharmacokinetic differences between unfractionated heparin and LMWH. (2) DOAC should be preferred over VKA after a recent stroke due to the growing body of evidence that they are associated with better outcomes. Interestingly and in contrast to another recent study from Europe and Japan6 that found DOACs to be associated with lower risk of intracerebral hemorrhage but no difference in the risk of recurrent stroke, Yaghi et al5 found that DOAC therapy decreased the risk of early recurrence but did not find any difference in rates of symptomatic intracranial hemorrhage. These conflicting results are possibly related to differing observational periods (90 days in Yaghi et al5 and up to 5.4 years in the European/Japanese study) and diverging development of the risk of hemorrhage and stroke over time. However, both studies found that DOACs were associated with better outcomes compared to VKA.Although the study by Yaghi et al5 helps us with the how—avoid bridging, use DOACs—the when is still a matter of debate. Currently, 4 large randomized controlled trials—ELAN (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischemic Stroke Patients With Atrial Fibrillation; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03148457), OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke; URL: http://www.isrctn.com; Unique identifier: ISRCTN17896007), TIMING (TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02961348), and START (Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03021928)1—are enrolling >10 000 patients all together explore the optimal timing of DOAC therapy after a recent stroke. Their results are eagerly awaited.DisclosuresDr Goeldlin received funding from the Schweizerische Akademie der Medizinischen Wissenschaften (SAMW)/Bangerter-Rhyner-Foundation (Young Talents in Clinical Research grant) and the Swiss Stroke Society Förderpreis. The other authors report no conflicts.FootnotesFor Disclosures, see page 2619.This manuscript was sent to Kazunori Toyoda, Guest Editor, for review by expert referees, editorial decision, and final disposition.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: David Seiffge, MD, Department of Neurology and Stroke Center, Inselspital, University Hospital, Freiburgstrasse, CH-3010 Bern, Switzerland. Email david.[email protected]chReferences1. Seiffge DJ, Werring DJ, Paciaroni M, Dawson J, Warach S, Milling TJ, Engelter ST, Fischer U, Norrving B. Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation.Lancet Neurol. 2019; 18:117–126. doi: 10.1016/S1474-4422(18)30356-9Google Scholar2. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, et al.. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.Lancet. 2014; 383:955–962. doi: 10.1016/S0140-6736(13)62343-0CrossrefMedlineGoogle Scholar3. Yoon CH, Park YK, Kim SJ, Lee MJ, Ryoo S, Kim GM, Chung CS, Lee KH, Kim JS, Bang OY. Eligibility and preference of new oral anticoagulants in patients with atrial fibrillation: comparison between patients with versus without stroke.Stroke. 2014; 45:2983–2988. doi: 10.1161/STROKEAHA.114.005599LinkGoogle Scholar4. Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial.Lancet. 2000; 355:1205–1210. doi: 10.1016/s0140-6736(00)02085-7CrossrefMedlineGoogle Scholar5. Yaghi S, Mistry E, Liberman AL, Giles G, Asad D, Liu A, Nagy M, Kaushal A, Azher I, Mac Grory B, et al.. Anticoagulation type and early recurrence in cardioembolic stroke: the IAC study.Stroke. 2020; 51:2724–2732. doi: 10.1161/STROKEAHA.120.028867LinkGoogle Scholar6. Seiffge DJ, Paciaroni M, Wilson D, Koga M, Macha K, Cappellari M, Schaedelin S, Shakeshaft C, Takagi M, Tsivgoulis G, et al.; CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators. Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation.Ann Neurol. 2019; 85:823–834. doi: 10.1002/ana.25489Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesAnticoagulation Type and Early Recurrence in Cardioembolic StrokeShadi Yaghi, et al. Stroke. 2020;51:2724-2732 September 2020Vol 51, Issue 9Article InformationMetrics Download: 7,755 © 2020 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.030997PMID: 32757754 Originally publishedAugust 6, 2020 Keywordsrisk factoratrial fibrillationhemorrhageanticoagulantsEditorialsPDF download SubjectsIschemic StrokeCerebrovascular Disease/Stroke
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