Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke

Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen B.; Schwab, Stefan; Köhrmann, Martin

doi:10.1016/j.jstrokecerebrovasdis.2016.06.031

Cited by 42 publications

(27 citation statements)

References 10 publications

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“…As advanced age is not a contraindication to the use of rivaroxaban [14], he was treated with this DOAC at the dose of 15 mg/die starting 5 days after the index event, despite the presence of intraventricular bleeding occurred after the thrombolytic therapy for the first event. Our results are even more encouraging given that randomized clinical trials with DOACs have excluded acute ischemic stroke patients, and the safety of DOAC administration soon after an index event has only been addressed by observational, prospective, and non-randomized studies [8][9][10][11][12][13]. In particular, in two prospective studies, the treatment with DOACs was commenced after a mean time of four and five days from the index event and no intracranial bleeding was observed during hospitalization [8,13], suggesting the safety of the early use of DOACs after an ischemic episode.…”

Section: Discussionmentioning

confidence: 71%

“…However, randomized clinical trials on DOACs have systematically excluded patients with recent ischemic stroke (<7 days) in whom the risk of sHT is higher [4][5][6][7]. Despite the lack of conclusive clinical evidence, the available data from observational, longitudinal studies suggest that the early use of DOACs is safe and might reduce the risk of sHT [8][9][10][11][12][13]. Therefore, in clinical practice, these agents are perceived as safe and increasingly used even during the first days after ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

Gentile¹,

Aless²,

Adami³

2017

JNSK

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In the setting of acute cardioembolic stroke, poor evidence exists on the use of anticoagulation early after the event, as well as in the presence of intraventricular bleeding. Moreover, the best timing to start therapy remains controversial for the high risk of hemorrhagic transformation (HT). Here, we describe the case of an 88-year-old man with atrial fibrillation (AF) and an acute ischemic stroke, who experienced early ischemic stroke recurrence and intraventricular bleeding after thrombolysis. Despite intraventricular bleeding and in light of the reduced kidney function, the decision was made to administer rivaroxaban 15 mg/die starting 5 days after the index event. The early use of rivaroxaban 15 mg/die was associated with clinical improvement in the absence of symptomatic HT and radiological worsening of intraventricular bleeding, and the pre-existing bleeding was regularly reabsorbed. Notably, 1 year after the ischemic stroke, the patient was still on oral anticoagulation with rivaroxaban 15 mg/die, without occurrence of hemorrhagic complications. To our knowledge, this is the first evidence of the efficacy and safety of early anticoagulation with rivaroxaban 15 mg/die after an acute ischemic stroke and early stroke recurrence despite the presence of intraventricular bleeding. Due to the early ischemic recurrence, the decision was made to start anticoagulant therapy despite the presence of ventricular bleeding, and in the absence of contraindications to the use of rivaroxaban [14], it was deemed, at the dose of 15 mg/die, as the optimal strategy due to the patient's reduced glomerular filtration rate (34 ml/min) [5,15]. During the following days, the neurological conditions of the patient improved, with amelioration of both motor and language symptoms. On day 11, a brain CT demonstrated the reabsorption of the intraventricular bleeding without occurrence of new ischemic lesions ( Figure 1G). On discharge, the NIHSS score was 2 and the patient was prescribed home treatment with rivaroxaban. At the 3-month follow-up, the patient had resumed his occupation as farmer and, 1 year after the ischemic stroke, he was still on oral anticoagulation with rivaroxaban 15 mg/die, without reporting hemorrhagic complications. Keywords: DiscussionIn patients with acute cardioembolic stroke, the best time to start anticoagulation remains controversial due to the risk of sHT. As DOACs display a lower intracranial bleeding risk compared to the VKAs, initiation of DOAC therapy has been proposed to follow the 'rule of thumb' of 1-3-6-12: 1 day after a transient ischemic attack (TIA), 3 days after a non-disabling stroke, 6 days after a moderate stroke, and at least 12 days after a severe stroke [14]. However, additional clinical evidence is needed to draw definitive conclusions on this crucial issue.Here, we describe the case of an elderly AF patient with an acute ischemic stroke, who required prompt anticoagulation for early recurrence. As advanced age is not a contraindication to the use of rivaroxaban [14], he was tr...

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

Gentile¹,

Aless²,

Adami³

2017

JNSK

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“…Однако имеющихся ре-зультатов отдельных регистров больных, перенесших ОНМК [15,16,[19][20][21][22][23][24], недостаточно для оценки каче-ства медикаментозного лечения, его динамики в ходе проспективного наблюдения данной категории боль-ных в амбулаторно-поликлинической практике в Рос-сийской Федерации [25][26][27].…”

Section: Outpatient Registry Of Stroke -Region амбулаторный регистр мunclassified

Drug Treatment of Patients With the History of Acute Stroke: Data of the Pilot Phase of the Outpatient Registry «region»

Boytsov

Lukyanov

Yаkushin

et al. 2017

Racionalʹnaâ farmakoterapiâ v kardiologii

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1 Государственный научно-исследовательский центр профилактической медицины Россия, 101990, Москва, Петроверигский пер., 10 2 Рязанский государственный медицинский университет имени академика И.П. Павлова Россия, 390026, Рязань, ул. Высоковольтная, 9 3 Российский национальный исследовательский медицинский университет им. Н. И. Пирогова Россия, 117997, Москва, ул. Островитянова, 1Цель. Оценить медикаментозное лечение больных, перенесших острое нарушение мозгового кровообращения (ОНМК), в рамках проспективных амбулаторных регистров. Материал и методы. В амбулаторный регистр больных, перенесших ОНМК любой давности (регистр ОНМК-ЛД), а также в амбулаторный регистр первого обращения (ОНМК-ПО) в поликлинику после перенесенного мозгового инсульта на базе одной из поликлиник г. Рязани были включены в рамках пилотного этапа, соответственно, 200 и 115 пациентов. В ходе проспективного наблюдения оценены соответствие на-значенной и реально принимаемой медикаментозной терапии клиническим рекомендациям, ее преемственность, а также приверженность пациентов лечению. Результаты. На амбулаторном этапе, особенно в период до референсного ОНМК, большинство больных не получало адекватной терапии для снижения риска развития ОНМК и других сердечно-сосудистых осложнений. В регистре ОНМК-ПО, по сравнению с регистром ОНМК-ЛД (в нем дата развития ОНМК была в среднем на 4,8 года раньше), в постинсультном периоде значимо чаще (р<0,05) назначались лекарственные препараты с доказанным благоприятным действием на прогноз (в т.ч. статины при ОНМК -46,9% по сравнению с 11%; статины при ише-мической болезни сердца (ИБС) -43% и 10,3%; антиагреганты при ИБС без фибрилляции предсердий -57,7% и 27%, антикоагулянты при фибрилляции предсердий -17,6% и 2,3%). Через 3 года наблюдения в регистре ОНМК-ЛД и 2 года -в регистре ОНМК-ПО частота при-нимаемой терапии значимо не отличалась от частоты назначений на этапе включения в регистры, за исключением статинов (их принимали в 1,7 и 1,5 раз реже). Прогностически значимые назначения этапа включения выполнялись в отдаленном периоде наблюдения в 49% и 70% случаев (в среднем 58%), соответственно, однако частота впервые назначенной терапии составила 44% и 19% от общего числа назначе-ний в данном периоде, соответственно. Согласно опроснику Мориски-Грина приверженными лечению были 17,7 и 51,7% пациентов, со-ответственно. Заключение. Результаты пилотного этапа исследования РЕГИОН (амбулаторные регистры ОНМК-ЛД и ОНМК-ПО) показали, что качество назначенной медикаментозной терапии пациентов в поликлинике является недостаточным. Сравнение данных регистров ОНМК-ЛД и ОНМК-ПО позволяет сделать предварительный вывод о том, что за 5-летний период, разделяющий давность развития ОНМК в этих регистрах, ка-чество лечения пациентов значительно улучшилось, хотя и в недостаточной степени. На этапе отдаленного проспективного наблюдения доля выполнения сделанных ранее прогностически значимых назначений составила в среднем лишь около 60%. В целом за время наблюдения, с учетом вновь сделанных назначений частота проведения должной медикаме...

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“…For heparins in therapeutic doses, on the other hand, a high risk of bleeding is known from previous studies in acute stroke, which is why these rare highrisk constellations remain under strict risk-benefit assessment (e. g., mechanical valve prosthesis in mitral position, vessel dissection) [57]. Once intracranial hemorrhage is excluded by imaging studies, the start of oral anticoagulation is currently individualized, taking into account the size of the infarction, clinical condition of the patient, risk of embolism, blood pressure control, concomitant medication and other factors usually between day 1 and day 12 after cardioembolic stroke [44,58].…”

Section: Antithrombotic Therapymentioning

confidence: 99%

Cardiac Arrhythmia following Stroke

Kallmünzer

Schwab

2017

Neurology International Open

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The autonomous innervation of the heart is based on a complex interaction of central and peripheral mechanisms in sympathetic and parasympathetic parts of the autonomic nervous system (▶Fig. 1). An extrinsic cardiac innervation is distinguished from an intrinsic one. Extrinsic systemTo put it simply, a center of the efferent parasympathetic innervation of the heart is found in the nucleus of the medulla oblongata, especially in the nucleus dorsalis [1]. The preganglionic fibers leave the central nervous system along with the vagus nerve and are connected to the second neuron in cardiac ganglion cells. Sympath etic fibers, on the other hand, originate from the nucleus intermediolateralis of the upper thoracic cord [2]. They reach the plexus cardiacus by means of the so-called "cardiac nerves" (usually 4 right-sided and 3 left-sided nervi cardiaci), after interposition in the border ganglia, especially in the ganglion stellatum. For the control of cardiac functions, the profound part of the plexus cardiacus is decisive; it extends between the tracheal bifurcation and the aortic arch, divides into a right and left half and in its further course follows the right or left coronary artery. The function of the efferent limb is modified by afferents from various organ systems, including the gastrointestinal tract or the carotissinus, by means of multisynaptic reflex arcs (e. g., baroreflex) [1]. In addition, in the blood circulating catecholamine, the release of which in the adrenal system is also subject to the autonomic system, mediates beta-adrenergic effects on the myocardium. It is postulated that dysbalances in the extrinsic system, in particular the pathological disinhibition of sympathetic activity, are relevant to the development of cardiac arrhythmias [1,[3][4][5]. For example, extensive brain stem damage can lead to suppression of central parasympathetic functions and overcoming of sympathetic tone [6], thus promoting the occurrence of cardiac arrhythmias. Conversely, blockade of the ganglion stellatum or renal sympathetic denervation should reduce the risk of ventricular arrhythmias in patients with prolonged-QT syndromes [7]. It is noteworthy in this context that extensive cardiac denervation, which may be present after orthotopic heart transplantation, is associated with a lower risk of supra ventricular rhythm disturbances, especially atrial fibrillation [8]. In these cases, the denervation should have protective effects and protect the myocardium from the autonomic imbalances of the extrinsic system before transmission. It should be noted, however, that organ donors are usually much younger and the vascular damage to the donor organs is often less pronounced, which significantly reduces the risk of atrial fibrillation independent of cardiac denervation [9].

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Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke

Cited by 42 publications

References 10 publications

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

Early Anticoagulation for Recurrent Ischemic Stroke despite the Presence of Ventricular Bleeding

Drug Treatment of Patients With the History of Acute Stroke: Data of the Pilot Phase of the Outpatient Registry «region»

Cardiac Arrhythmia following Stroke

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