ENOS研究显示，经皮硝酸甘油(GTN)可降低血压但并未改善急性卒中患者的功能转归。然而，如果患者在卒中发病6小时之内被随机化，GTN则与其转归改善有关。

        美国学者近期开展了一项预设亚组分析，纳入629例脑出血发生48小时之内且收缩压≥140 mm Hg的受试者，评估GTN(5 mg/d，治疗7天)和无GTN的效果。主要转归为90天时患者的改良Rankin评分。

        结果显示，患者们的基线平均血压为172/93 mm Hg，与未接受GTN治疗的319例患者相比，被分入GTN组的310例患者在第一天时血压明显降低(降低了7.5/4.2 mm Hg，P≤0.05);但二者的改良Rankin评分无差异(GTN转归恶化的校正比值比为1.04;95%置信区间为0.78–1.37;P=0.84)。

        在发病6小时内的61例亚组患者中，GTN可改善患者功能转归(比值比0.22;95%置信区间0.07–0.69;P=0.001)。两组之间严重不良事件发生率无显著差异。

        该研究表明，在脑出血发病48小时内的患者中，GTN可安全降低血压水平，但并不改善其功能转归。极早期治疗可能使患者获益但需进一步评估。

        相关研究12月8日在线发表于《卒中》(Stroke)杂志。

        原文

STROKEAHA.115.010368Published online before print December 8, 2015,doi: 10.1161/STROKEAHA.115.010368
Glyceryl Trinitrate for Acute Intracerebral Hemorrhage
Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis
1. Kailash Krishnan, MRCP,
2. Polly Scutt, MSc,
3. Lisa Woodhouse, MSc,
4. Alessandro Adami, MD,
5. Jennifer L. Becker, MD, FRCR,
6. Eivind Berge, MD, PhD,
7. Lesley A. Cala, MD, FRCR,
8. Ana M. Casado, MD,
9. Valeria Caso, MD, PhD,
10. Christopher Chen, MRCP, FAMS,
11. Hanna Christensen, MD, PhD,
12. Ronan Collins, MD, FRCPI,
13. Anna Czlonkowska, MD, PhD,
14. Robert A. Dineen, PhD, FRCR,
15. John Gommans, FRACP,
16. Panos Koumellis, MRCP, FRCR,
17. Kennedy R. Lees, MD, FRCP,
18. George Ntaios, MD, PhD,
19. Serefnur Ozturk, MD,
20. Stephen J. Phillips, MD, FRCPC,
21. Stuart J. Pocock, MSc, PhD,
22. Asita de Silva, DPhil, FRCP,
23. Nikola Sprigg, DM, MRCP,
24. Szabolcs Szatmari, MD,
25. Joanna M. Wardlaw, FRCR, FMedSci and
26. Philip M. Bath, FRCP, DSc
-Author Affiliations
1. From the Stroke Trials Unit, Division of Clinical Neuroscience (K.K., P.S., L.W., N.S., P.M.B.) and Radiological Sciences Research Group, Division of Clinical Neuroscience (R.A.D.), University of Nottingham, Nottingham, United Kingdom; Stroke Centre, Ospedale Sacro Cuore, Verona, Italy (A.A.); Department of Medical Imaging, College of Medicine, The University of Arizona, Tucson (J.L.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia (L.A.C.); Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Western General Hospital, Edinburgh, United Kingdom (A.M.C., J.M.W.); Stroke Unit, Santa Maria Hospital, University of Perugia, Perugia, Italy (V.C.); Department of Pharmacology, National University of Singapore, Singapore, Singapore (C.C.); Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark (H.C.); Stroke Service, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland (R.C.); Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); Department of Medicine, Hawke’s Bay Hospital, Hastings, New Zealand (J.G.); Department of Neuroradiology, Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, United Kingdom (P.K.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey (S.O.); Division of Neurology, Dalhousie University, Halifax, Canada (S.J. Phillips); Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom (S.J. Pocock); Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka (A.d.S.); and Department of Neurology, Clinical County Emergency Hospital, Targu Mures, Romania (S.S.).
1. Correspondence to Philip M. Bath, FRCP, DSc, Stroke, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, United Kingdom. E-mail philip.bath@nottingham.ac.uk
Abstract
Background and Purpose—The Efficacy of Nitric oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset.
Methods—In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days.
Results—Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference −7.5/−4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78–1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07–0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN.
Conclusions—In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies.