Robinson Thompson G, Wang Xia, Arima Hisatomi, Bath Philip M, Billot Laurent, Broderick Joseph P, Demchuk Andrew M, Donnan Geoffery A, Kim Jong S, Lavados Pablo M, Lee Tsong-Hai, Lindley Richard I, Martins Sheila C O, Olavarria Veronica V, Pandian Jeyaraj D, Parsons Mark W, Pontes-Neto Octavio M, Ricci Stefano, Sato Shoichiro, Sharma Vijay K, Nguyen Thang H, Wang Ji-Guang, Woodward Mark, Chalmers John, Anderson Craig S
From the Department of Cardiovascular Sciences, National Institute for Health Research Biomedical Research Unit, University of Leicester, (T.G.R.); George Institute for Global Health, Neurological and Mental Health Division (X.W., H.A., L.B., R.I.L., M.W., J.C., C.S.A.), Faculty of Medicine, University of New South Wales (X.W., H.A., L.B., M.W., J.C., C.S.A.), and Department of Geriatric Medicine, Westmead Clinical School (R.I.L.), University of Sydney, Australia; Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, United Kingdom (P.M.B.); Department of Neurology and Rehabilitation Medicine, University of Cincinnati Neuroscience Institute (J.P.B.); Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Canada (A.M.D.); Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia (G.A.D.); Department of Neurology, Asan Medical Center, University of Ulsan, Seoul, Korea (J.S.K.); Department of Neurology and Psychiatry, Clinica Alemana de Santiago, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Chile (P.M.L., V.V.O.); Departamento de Ciencias Neurológicas, Facultad de Medicina, Universidad de Chile, Santiago (P.M.L.); Department of Neurology, Stroke Center, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (T.-H.L.); Stroke Division of Neurology Service, Hospital de Clinicas de Porto Alegre, University of Rio Grande do Sul, Brazil (S.C.O.M.); Department of Neurology, Christian Medical College, Ludhiana, Punjab, India (J.D.P.); Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (M.W.P.); Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Brazil (O.M.P.-N.); Uo Neurologia, USL Umbria 1, Sedi di Citta di Castello e Branca, Italy (S.R.); Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (S.S.); Yong Loo Lin School of Medicine, National University of Singapore (V.K.S.); Division of Neurology, National University Hospital, Singapore (V.K.S.); Department of Cerebrovascular Disease, 115 People's Hospital, Ho Chi Minh City, Vietnam (T.H.N.); The Shanghai Institute for Hypertension, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, China (J.-G.W.); Department of Epidemiology, Johns Hopkins University, Baltimore, MD (M.W.); George Institute for Global Health, University of Oxford, United Kingdom (M.W.); Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (C.S.A.); and The George Institute China, Peking University Health Sciences Center, Beijing (C.S.A.).
Stroke. 2017 Jul;48(7):1877-1883. doi: 10.1161/STROKEAHA.116.016274. Epub 2017 Jun 15.
Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study).
Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2-6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria.
There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81-1.26; =0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75-1.20; =0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87-1.21; =0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00-3.30; =0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant (-trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2-6; OR, 0.84; 95% CI, 0.62-1.12 versus OR, 1.16; 95% CI, 0.99-1.36).
Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.
许多接受急性缺血性卒中溶栓治疗的患者之前接受过抗血小板治疗（APT），这可能会增加症状性脑出血的风险。在一项预先设定的亚组分析中，我们报告了国际多中心ENCHANTED研究（强化高血压控制与溶栓治疗卒中研究）参与者中，根据之前是否使用APT，不同剂量静脉注射阿替普酶的对比效果。
在3285例接受阿替普酶治疗的患者（平均年龄66.6岁；38%为女性）中，这些患者在症状发作4.5小时内被随机分配接受低剂量（0.6mg/kg）或标准剂量（0.9mg/kg）静脉注射阿替普酶，其中752例（22.9%）报告之前使用过APT。90天时的主要结局是死亡或残疾的联合终点（改良Rankin量表[mRS]评分，2 - 6分）。其他结局包括mRS评分3至6分、mRS序数变化以及根据各种标准标准判定的症状性脑出血。
在对第一周的基线特征和管理因素进行调整后，之前接受过APT的患者与未接受过APT的患者在结局方面没有显著差异；以mRS评分2至6分定义（调整后的优势比[OR]，1.01；95%置信区间[CI]，0.81 - 1.26；P = 0.953），3至6分（OR，0.95；95% CI，0.75 - 1.20；P = 0.662），或mRS序数变化（OR，1.03；95% CI，0.87 - 1.21；P = 0.770）。根据卒中监测研究溶栓安全实施定义，之前接受过APT的阿替普酶治疗患者有更高的症状性脑出血发生率（OR，1.82；95% CI，1.00 - 3.30；P = 0.051）。尽管不显著（P趋势，0.053），但与未使用APT的患者相比，之前接受过APT的患者中，低剂量阿替普酶的结局倾向于比标准剂量阿替普酶更好（mRS评分2 - 6分；OR，0.84；95% CI，0.62 - 1.12对比OR，1.16；95% CI，0.99 - 1.36）。
低剂量阿替普酶可能会改善之前接受过APT的溶栓治疗急性缺血性卒中患者的结局，但这需要在随机对照试验中进一步评估。
