一项研究表明,对于脑出血 (ICH),借助药物降低血压 (BP) 可减少复发事件。[115]Chapman N, Huxley R, Anderson C, et al. Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial. Stroke. 2004 Jan;35(1):116-21.https://www.ahajournals.org/doi/full/10.1161/01.str.0000106480.76217.6fhttp://www.ncbi.nlm.nih.gov/pubmed/14671247?tool=bestpractice.com 应严格控制患者的血压,这对于那些出血位置为典型高血压血管病变部位的患者尤为重要。一些研究显示,降低血压至<130/90 mmHg 可显著减少脑内出血 (ICH) 复发的风险。[54]Hemphill JC 3rd, Greenberg SM, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60.https://www.ahajournals.org/doi/full/10.1161/str.0000000000000069http://www.ncbi.nlm.nih.gov/pubmed/26022637?tool=bestpractice.com 其他研究证明,如此强化降低收缩压 (SBP) 不能增加临床获益,也不能降低死亡率和残疾率。实际上,收缩压 (SBP) 为 110-139 mmHg 的患者,发生肾损伤的比例高于目标血压为 140-179 mmHg 的患者。因此,建议将 SBP 降至 140-179 mmHg。[60]Qureshi AI, Palesch YY, Barsan WG, et al.; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43.http://www.ncbi.nlm.nih.gov/pubmed/27276234?tool=bestpractice.com 美国心脏病学会/美国心脏协会 (American College of Cardiology/American Heart Association) 指南建议二级卒中预防的目标血压为<130 mmHg/80 mmHg。[116]Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):e13-115.https://www.ahajournals.org/doi/full/10.1161/HYP.0000000000000065http://www.ncbi.nlm.nih.gov/pubmed/29133356?tool=bestpractice.com
在为了预防心源性栓塞性卒中或血栓栓塞而使用抗凝治疗却导致 ICH 的情况下,确定重新开始抗凝是否恰当存在困难。一方面,重新开始抗凝可能会增加 ICH 复发的风险;[117]Murthy SB, Gupta A, Merkler AE, et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke. 2017 Jun;48(6):1594-600.https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.116.016327http://www.ncbi.nlm.nih.gov/pubmed/28416626?tool=bestpractice.com 然而,另一方面,不进行抗凝可能增加血栓栓塞的风险。总体而言,应避免 ICH 后使用抗凝药物,除非存在人工心脏瓣膜或其他类似的绝对适应证。[118]Eckman MH, Rosand J, Knudsen KA, et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003 Jul;34(7):1710-6.https://www.ahajournals.org/doi/full/10.1161/01.str.0000078311.18928.16http://www.ncbi.nlm.nih.gov/pubmed/12805495?tool=bestpractice.com 美国卒中协会 (American Stroke Association) 指南建议,避免在脑叶出血后恢复使用口服抗凝剂,而在非肺叶 ICH 的情况下仍可考虑使用。[54]Hemphill JC 3rd, Greenberg SM, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60.https://www.ahajournals.org/doi/full/10.1161/str.0000000000000069http://www.ncbi.nlm.nih.gov/pubmed/26022637?tool=bestpractice.com 一项 meta 分析显示,恢复口服抗凝剂可能仍与死亡率降低和结局良好相关,因为抗凝相关 ICH 合并心房颤动的幸存者发生缺血性卒中的风险高于 ICH 复发的风险。[119]Biffi A, Kuramatsu JB, Leasure A, et al. Oral anticoagulation and functional outcome after intracerebral hemorrhage. Ann Neurol. 2017 Nov;82(5):755-65.http://www.ncbi.nlm.nih.gov/pubmed/29028130?tool=bestpractice.com 维生素 K 拮抗剂华法林通常是重新开始抗凝治疗时的首选抗凝剂,可能是因为其可逆性,但数据表明新型口服抗凝剂与自发性 ICH 的相关性较弱。[120]Hobbs FR, Taylor CJ, Jan Geersing G, et al. European Primary Care Cardiovascular Society (EPCCS) consensus guidance on stroke prevention in atrial fibrillation (SPAF) in primary care. Eur J Prev Cardiol. 2016 Mar;23(5):460-73.http://journals.sagepub.com/doi/10.1177/2047487315571890http://www.ncbi.nlm.nih.gov/pubmed/25701017?tool=bestpractice.com[121]Katsanos AH, Mavridis D, Parissis J, et al. Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis. Ther Adv Neurol Disord. 2016 Sep;9(5):359-68.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994786/http://www.ncbi.nlm.nih.gov/pubmed/27582891?tool=bestpractice.com[122]Bentz BA. Nonvitamin K antagonist oral anticoagulants in everyday practice: Stroke prevention in atrial fibrillation and treatment of venous thromboembolism. J Am Assoc Nurse Pract. 2015 Dec;27(12):721-31.http://www.ncbi.nlm.nih.gov/pubmed/26676209?tool=bestpractice.com 当使用新型口服抗凝剂治疗导致继发性 ICH 时,这些药物与更小的血肿和更好的功能结局相关。[117]Murthy SB, Gupta A, Merkler AE, et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke. 2017 Jun;48(6):1594-600.https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.116.016327http://www.ncbi.nlm.nih.gov/pubmed/28416626?tool=bestpractice.com[123]Oertel LB, Fogerty AE. Use of direct oral anticoagulants for stroke prevention in elderly patients with nonvalvular atrial fibrillation. J Am Assoc Nurse Pract. 2017 Sep;29(9):551-61.http://www.ncbi.nlm.nih.gov/pubmed/28805310?tool=bestpractice.com[124]Raccah BH, Perlman A, Danenberg HD, et al. Major bleeding and hemorrhagic stroke with direct oral anticoagulants in patients with renal failure: systematic review and meta-analysis of randomized trials. Chest. 2016 Jun;149(6):1516-24.http://www.ncbi.nlm.nih.gov/pubmed/26836922?tool=bestpractice.com
在考虑重新开始抗凝治疗时,必须权衡缺血性卒中的风险与出血的风险。尚不清楚重新开始抗凝治疗的最佳时机。等待至少 4 周是合理的,尤其是对于没有机械性心脏瓣膜的患者。[54]Hemphill JC 3rd, Greenberg SM, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60.https://www.ahajournals.org/doi/full/10.1161/str.0000000000000069http://www.ncbi.nlm.nih.gov/pubmed/26022637?tool=bestpractice.com 阿司匹林似乎对 ICH 复发风险增加有相对轻微的作用,因而可以考虑在血栓事件高风险患者中谨慎使用,甚至可在继发性 ICH 后使用。[125]Perry LA, Berge E, Bowditch J, et al. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2017 May 25;(5):CD012144.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD012144.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28540976?tool=bestpractice.com 应当注意的是,一项队列研究显示,在接受以每日阿司匹林为基础的抗血小板治疗而不常规使用质子泵抑制剂 (proton-pump inhibitor, PPI) 的患者中,与较年轻患者相比,老年患者发生严重出血的风险更高,并且面临该风险的时间更长。这项研究显示,在 75 岁或 75 岁以上的患者中,严重出血事件有一半发生在上消化道。需常规给予PPI 治疗对严重上消化道出血进行预防的患者数较少,研究者们总结得出,应鼓励联合用药。[126]Li L, Geraghty OC, Mehta Z, et al. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017 Jul 29;390(10093):490-9.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30770-5/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/28622955?tool=bestpractice.com
对于心房颤动伴抗凝相关 ICH 的患者,左心耳 (LAA) 封堵装置可能是抗凝治疗的一种替代方案。与安慰剂相比,LAA 手术作为抗栓塞干预取得了早期成功;然而,需要更多的数据来确定该手术相对于抗凝治疗的安全性和有效性。[127]Tereshchenko LG, Henrikson CA, Cigarroa J, et al. Comparative effectiveness of interventions for stroke prevention in atrial fibrillation: a network meta-analysis. J Am Heart Assoc. 2016 May 20;5(5): e003206.https://www.ahajournals.org/doi/10.1161/JAHA.116.003206http://www.ncbi.nlm.nih.gov/pubmed/27207998?tool=bestpractice.com
基于患者在出血原因检查中所发现的卒中危险因素和相关疾病,患者可能需要采取一些其他的二级预防措施。