Summary Background Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) ...is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. Methods We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov , number NCT00928915. Findings Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7–197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). Interpretation In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA. Funding Octapharma.
In a previous phase 2 placebo-controlled trial, recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcome in patients with intracerebral ...hemorrhage. Those findings were not reproduced in this phase 3 trial, in which rFVIIa reduced hematoma growth but did not improve clinical outcomes.
In this phase 3 trial, recombinant activated factor VII (rFVIIa) reduced hematoma growth but did not improve clinical outcomes in patients with intracerebral hemorrhage.
Intracerebral hemorrhage is the most devastating form of stroke. Approximately 40% of patients with intracerebral hemorrhage die within 30 days, and the majority of survivors are left with severe disability.
1
,
2
Hematoma growth occurs in up to 70% of patients who have intracerebral hemorrhage documented by computed tomographic (CT) scanning performed within 3 hours after the onset of symptoms.
3
,
4
Furthermore, hemorrhage expansion is an independent determinant of death and disability.
4
In addition to intracerebral-hemorrhage growth, other predictors of poor outcome include age, baseline volume of the hemorrhage, Glasgow Coma Scale score, intraventricular hemorrhage, and infratentorial location.
5
There is no . . .
IMPORTANCE: Intracerebral hemorrhage (ICH) is the most devastating adverse event in patients receiving oral anticoagulation. There is only sparse evidence regarding ICH related to the use of ...non–vitamin K antagonist oral anticoagulant (NOAC) agents. OBJECTIVE: To evaluate the early clinical and radiological course, acute management, and outcome of ICH related to NOAC use. DESIGN, SETTING, AND PARTICIPANTS: Prospective investigator-initiated, multicenter observational study. All diagnostic and treatment decisions, including administration of hemostatic factors (eg, prothrombin complex concentrate), were left to the discretion of the treating physicians. The setting was 38 stroke units across Germany (February 1, 2012, to December 31, 2014). The study included 61 consecutive patients with nontraumatic NOAC-associated ICH, of whom 45 (74%) qualified for the hematoma expansion analysis. MAIN OUTCOMES AND MEASURES: Hematoma expansion, intraventricular hemorrhage, and reversal of anticoagulation during the acute phase. Recorded were the 3-month functional outcome, factors associated with an unfavorable outcome (modified Rankin Scale score, 3-6), any new intraventricular extension or an increase in the modified Graeb score by at least 2 points, and the frequency of substantial hematoma expansion (defined as relative ≥33% or absolute ≥6-mL volume increase). RESULTS: In total, 41% (25 of 61) of patients with NOAC-associated ICH were female, and the mean (SD) patient age was 76.1 (11.6) years. At admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range, 4-18). The mean (SD) baseline hematoma volume was 23.7 (31.3) mL. In patients with sequential imaging for the hematoma expansion analysis, substantial hematoma expansion occurred in 38% (17 of 45). New or increased intraventricular hemorrhage was observed in 18% (8 of 45). Overall mortality was 28% (17 of 60 follow-up data were missing in 1 patient) at 3 months, and 65% (28 of 43) of survivors had an unfavorable outcome (modified Rankin Scale score, 3-6). Overall, 57% (35 of 61) of the patients received prothrombin complex concentrate, with no statistically significant effect on the frequency of substantial hematoma expansion (43% 12 of 28 for prothrombin complex concentrate vs 29% 5 of 17 for no prothrombin complex concentrate, P = .53, or on the occurrence of an unfavorable outcome (modified Rankin Scale score, 3-6) (odds ratio, 1.20; 95% CI, 0.37-3.87; P = .76). CONCLUSIONS AND RELEVANCE: Non–vitamin K antagonist oral anticoagulant–associated ICH has a high mortality and an unfavorable outcome, and hematoma expansion is frequent. Larger-scale prospective studies are needed to determine whether the early administration of specific antidotes can improve the poor prognosis of NOAC-associated ICH.
The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November ...2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).
BACKGROUND AND PURPOSE:We determined the rates and predictors of acute kidney injury (AKI) and renal adverse events (AEs), and effects of AKI and renal AEs on death or disability in patients with ...intracerebral hemorrhage.
METHODS:We analyzed data from a multicenter trial which randomized 1000 intracerebral hemorrhage patients with initial systolic blood pressure ≥180 mm Hg to intensive (goal 110–139 mm Hg) over standard (goal 140–179 mm Hg) systolic blood pressure reduction within 4.5 hours of symptom onset. AKI was identified by serial assessment of daily serum creatinine for 3 days post randomization.
RESULTS:AKI and renal AEs were observed in 149 patients (14.9%) and 65 patients (6.5%) among 1000 patients, respectively. In multivariate analysis, the higher baseline serum creatinine (≥110 μmol/L) was associated with AKI (odds ratio 2.4 95% CI, 1.2–4.5) and renal AEs (odds ratio 3.1 95% CI, 1.2–8.1). Higher area under the curve for intravenous nicardipine dose was associated with AKI (odds ratio 1.003 95% CI, 1.001–1.005) and renal AEs (odds ratio 1.003 95% CI, 1.001–1.006). There was a higher risk to death (relative risk 2.6 95% CI, 1.6–4.2) and death or disability (relative risk 1.5 95% CI, 1.3–1.8) at 90 days in patients with AKI but not in those with renal AEs.
CONCLUSIONS:Intracerebral hemorrhage patients with higher baseline serum creatinine and those receiving higher doses of nicardipine were at higher risk for AKI and renal AEs. Occurrence of AKI was associated higher rates of death or disability at 3 months.
REGISTRATION:URLhttps://clinicaltrials.gov. Unique identifierNCT01176565.
Summary
Idarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect of dabigatran in animals and in healthy volunteers. The Study of ...the
REVERS
al
E
ffects of Idarucizumab in Patients on
A
ctive
D
abigatran (RE-VERSE AD™) is a global phase 3 prospective cohort study aimed at investigating idarucizumab in dabigatran-treated patients who present with uncontrollable or life-threatening bleeding, and in those requiring urgent surgery or intervention. We describe the rationale for, and design of the trial (clinicaltrials.gov NCT02104947).
Autonomic dysfunction, including increased sympathetic drive and blunted baroreflex, has repeatedly been observed in acute stroke. Of clinical importance is that the stroke-related autonomic ...imbalance seems to be linked to worse outcome after stroke. Here, we discuss the role of baroreflex impairment in acute stroke and its possible pathophysiological and therapeutic relevance. Summary of Review- Possible mechanisms linking baroreflex impairment with unfavorable outcome in stroke may include increased cardiovascular morbidity and mortality, promotion of secondary brain injury due to local inflammation, hyperglycemia, or altered cerebral perfusion.
We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke.
In this randomized trial, treatment of patients with intracerebral hemorrhage with recombinant activated factor VII (rFVIIa) within four hours after the onset of bleeding reduced the growth of the ...hematoma and the rates of disability and mortality (90-day mortality was 18 percent with rFVIIa and 29 percent with placebo). Serious thromboembolic adverse events were more common among patients treated with rFVIIa than among those who received placebo.
Despite the higher rates of some complications, early treatment with rFVIIa improved functional outcomes and survival among patients with intracerebral hemorrhage.
Intracerebral hemorrhage is one of the most disabling forms of stroke. More than one third of patients with this disorder die within one month after the onset of symptoms, and only 20 percent regain functional independence.
1
There is currently no effective treatment for intracerebral hemorrhage.
2
The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage,
3
,
4
and early hematoma growth is an important cause of neurologic deterioration.
5
–
8
An increase in volume of more than 33 percent is detectable on repeated computed tomography (CT) in 38 percent of patients initially scanned within three . . .
Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent ...decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.
PDF
