Intracerebral Hemorrhage
Total Page:16
File Type:pdf, Size:1020Kb
Circulation Journal ORIGINAL ARTICLE Circ J 2019; 83: 441 – 446 doi: 10.1253/circj.CJ-18-0938 Stroke Safety of Anticoagulant Therapy Including Direct Oral Anticoagulants in Patients With Acute Spontaneous Intracerebral Hemorrhage Yuki Sakamoto, MD; Chikako Nito, MD, PhD; Yasuhiro Nishiyama, MD, PhD; Satoshi Suda, MD, PhD; Noriko Matsumoto, MD, PhD; Junya Aoki, MD, PhD; Takashi Shimoyama, MD, PhD; Takuya Kanamaru, MD, PhD; Kentaro Suzuki, MD; Takuya Nishimura, MD; Masahiro Mishina, MD, PhD; Kazumi Kimura, MD, PhD Background: Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (<7 days from onset), sponta- neous ICH were retrospectively enrolled from a prospective registry. Whether to start anticoagulation was at the attending physicians’ discretion, and thromboembolic or hemorrhagic events during hospitalization were analyzed. A total of 236 patients (80 women [34%]; median age 69 [interquartile range 61–79] years; National Institutes of Health stroke scale score 7 [3–16]) were enrolled. Of them, 47 patients (20%) had an indication for anticoagulant therapy (33 had atrial fibrillation, 14 developed deep vein thrombosis), and 41 of 47 patients (87%) were actually treated with anticoagulant therapy (DOACs were used in 34 patients) after a median of 7 days from ICH onset. There was neither hematoma expansion nor excessive hemorrhagic complications during hospitalization after starting anticoagulant therapy. Conclusions: Anticoagulant therapy was conducted for approximately 90% of anticoagulation-indicated patients after a median of 7 days from ICH onset. The predominant anticoagulant medications were DOACs. Anticoagulant therapy started from the acute phase of ICH should be safe. Key Words: Atrial fibrillation; Deep vein thrombosis; Direct oral anticoagulants; Intracerebral hemorrhage; Safety ntracerebral hemorrhage (ICH) is a devastating patients only with anticoagulation-related ICH. The safety hemorrhagic event associated with high mortality or and effectiveness of anticoagulant therapy in patients I severe neurological sequelae.1 One of the areas of with acute spontaneous intracerebral, not intracranial, uncertainty in managing ICH patients is whether to provide hemorrhage are not fully known. Moreover, the safety or anticoagulant therapy for those needing anticoagulation,2,3 effect of direct oral anticoagulants (DOACs) after ICH is especially in acute settings; ICH patients have a high risk also unknown. DOACs are theoretically more suitable of thromboembolic disease,4 but patients with a history of for patients with non-valvular atrial fibrillation (AF) or ICH carry a significant risk of recurrent ICH when treated deep vein thrombosis (DVT) and ICH, because ICH has with a vitamin K antagonist (VKA) after initial ICH.5 Past occurred less frequently in patients treated with DOACs retrospective studies suggested that initiating anticoagulant compared with those treated with a VKA in clinical trials.12–17 therapy after ICH in patients needing anticoagulation Thus the aims of the present study were to elucidate the might be beneficial, though optimal timing for starting current status and safety of anticoagulant therapy, including treatment was undetermined.6–10 However, the patients DOACs, for acute spontaneous ICH patients in real-world included in many past studies were heterogeneous in terms settings. of the type of hemorrhage (intracranial, not intracerebral, hemorrhage including traumatic, subarachnoid, subdural, and epidural hemorrhage),11 and most studies included Received August 22, 2018; revised manuscript received September 26, 2018; accepted November 17, 2018; J-STAGE Advance Publication released online December 27, 2018 Time for primary review: 27 days Department of Neurological Science (Y.S., C.N., Y.N., S.S., N.M., J.A., T.S., T.K., K.S., T.N., K.K.), Department of Neuro-pathophysiological Imaging (M.M.), Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Mailing address: Yuki Sakamoto, MD, Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. E-mail: [email protected] ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected] Circulation Journal Vol.83, February 2019 442 SAKAMOTO Y et al. Table 1. Patients’ Baseline Clinical Characteristics AC group Non-AC group Variable P value (n=41) (n=195) Female sex, n (%) 13 (32) 67 (34) 0.857 Age, years, median (IQR) 72 (65–80) 68 (59–78) 0.115 BMI, kg/m2, median (IQR) 23.0 (20.2–24.9) 22.2 (20.1–24.4) 0.416 Prior history of ischemic stroke, n (%) 10 (24) 11 (6) 0.001 Prior history of hemorrhagic stroke, n (%) 1 (2) 19 (10) 0.213 Vascular risk factor, n (%) Hypertension 35 (85) 163 (84) 1.000 Diabetes mellitus 13 (32) 35 (18) 0.056 Hyperlipidemia 12 (29) 50 (26) 0.697 Current smoking 10 (24) 54 (28) 0.847 Daily alcohol intake 23 (56) 100 (51) 0.609 Preadmission mRS score, median (IQR) 0 (0–1) 0 (0–0) 0.923 Initial NIHSS score, median (IQR) 11 (3–19) 7 (3–15) 0.336 Initial hematoma volume, ml, median (IQR) 8.0 (4.5–27.0) 6.6 (2.6–14.0) 0.119 Lobar hemorrhage, n (%) 10 (24) 29 (15) 0.164 Blood test results at admission, median (IQR) Hemoglobin, g/dL 13.7 (11.8–15.5) 13.6 (12.5–15.0) 0.735 Platelet count, ×104/μL 19.4 (16.8–22.7) 20.7 (16.8–24.6) 0.278 eGFR, mL/min/1.73 m2 60 (43–74) 72 (59–85) 0.002 Length of hospital stay, days, median (IQR) 21 (14–31) 16 (10–26) 0.026 mRS score at discharge, median (IQR) 4 (3–5) 4 (2–4) 0.445 AC group: patients treated with anticoagulant therapy during hospitalization. Non-AC group: patients not treated with anticoagulant therapy during hospitalization. AC, anticoagulation; BMI, body mass index; eGFR, estimated glomerular filtration rate; ICH, intracerebral hemorrhage; IQR, interquartile range; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale. Methods index ICH was counted as “history of hemorrhagic stroke”. Neurological severity was assessed using the National Subjects Institutes of Health Stroke Scale (NIHSS), and functional From September 2014 through March 2017, consecutive outcomes were evaluated using the modified Rankin Scale patients with acute (<7 days from onset), spontaneous (mRS). Anthropometric measurements and routine blood ICH admitted to our Stroke Unit (SU) were retrospectively biochemistry examinations were performed on admission. enrolled from a prospective registry. In general, acute ICH Hematoma volume was evaluated with non-contrast patients were admitted to the SU and antihypertensive computed tomography (CT) on admission using the ABC/2 treatment started as soon as possible, targeting systolic method. Magnetic resonance imaging, including T2*- blood pressure (BP) <140 mmHg. Patients with secondary gradient echo imaging (T2*), was performed during admis- ICH and/or who underwent surgical intervention in the sion, and the presence and location of cerebral microbleeds acute phase (<7 days from onset) were excluded. This were assessed using previously reported criteria.19 Cerebral study was approved by the institutional ethics committee. amyloid angiopathy (CAA) was diagnosed using modified Written, informed consent was obtained from all patients Boston criteria.20 AF was diagnosed with 12-lead ECG or or their next-of-kin. cardiac monitoring during the SU stay. DVT was diagnosed using lower extremity ultrasonography or enhanced CT. Clinical Characteristics Any thromboembolic and hemorrhagic events during Clinical background characteristics, including sex, age, hospitalization were collected from the medical charts. cardiovascular risk factors, and past medical histories, were recorded on admission. Cardiovascular risk factors Anticoagulant Therapy and Follow-up Imaging were defined as: (1) hypertension, history of using antihy- Whether to start anticoagulation was at the attending pertensive agents, systolic BP ≥140 mmHg, or diastolic BP physicians’ discretion. Detailed anticoagulant therapy ≥90 mmHg before or ≥2 weeks after stroke onset; (2) information, if started, including the timing, class (VKA, diabetes mellitus, use of hypoglycemic agents, random DOAC, or other), and dose, were collected. Hematoma glucose level ≥200 mg/dL, or glycosylated hemoglobin expansion after starting anticoagulant therapy was assessed ≥6.5% on admission; (3) hyperlipidemia, use of antihyper- with follow-up cranial CT. lipidemic agents, or a serum total cholesterol level ≥220 mg/dL; (4) current smoker; and (5) daily alcohol Statistical Analysis intake. The HAS-BLED score was calculated based on the All patients were divided into 2 groups: those treated with published guideline.18 Aortic plaque was not assessed as a anticoagulant therapy during hospitalization (AC group) component of the score. Because the present study aimed and those not (Non-AC group). First, clinical background to assess the safety of anticoagulant therapy after ICH, the characteristics were compared between groups. In addition, Circulation Journal Vol.83, February 2019 Anticoagulant Therapy in Acute ICH 443 Table 2. Baseline Clinical Characteristics of Anticoagulant-Indicated Patients With and Without Anticoagulation