Smoking influences outcome in patients who had thrombolysed ischaemic stroke:the ENCHANTED study

Background and purpose As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke(AIS),we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study(ENCHANTED).Methods Post-hoc analyses of ENCHANTED,an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS.Multivariable logistic regression models with inverse probability of treatment weighting(IPTW)propensity scores were used to determine associations of self-reported smoking status and clinical outcomes,according to 90-day modified Rankin Scale(mRS)scores and symptomatic intracerebral haemorrhage(sICH).Results Of 4540 patients who had an AIS,there were 1008(22.2%)current smokers who were younger and predominantly male,with more comorbidities of hypertension,coronary artery disease,atrial fibrillation and diabetes mellitus,and greater baseline neurological impairment,compared with non-smokers.In univariate analysis,current smokers had a higher likelihood of a favourable shift in mRS scores(OR 0.88,95%CI 0.77 to 0.99;p=0.038)but this association reversed in a fully adjusted model with IPTW(adjusted OR 1.15,95%CI 1.04 to 1.28;p=0.009).A similar trend was also apparent for dichotomised poor outcome(mRS scores 2–6:OR 1.18,95%CI 1.05 to 1.33;p=0.007),but not with the risk of sICH across standard criteria.Conclusion Smoking predicts poor functional recovery in patients who had thrombolysed AIS.Trial registration number NCT01422616.

Characteristics,management and response to alteplase in China versus non-China participants of the ENCHANTED trial

Background The characteristics of patients with acute ischaemic stroke(AIS)and their management vary across regions,which may influence outcomes.We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy(ENCHANTED),which tested different alteplase doses in AIS.Methods ENCHANTED was an international,multicentre,open,blinded-endpoint trial of the effects of low-dose(0.6 mg/kg)versus standard-dose(0.9 mg/kg)intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage(sICH)in 3310 patients with AIS.Results Participants(n=1419,48%)in China were younger,and more often male,hypertensive and with prior stroke and coronary artery disease,but less likely to have atrial fibrillation and use antihypertensive,antithrombotic and lipid-lowering agents,compared with non-China patients with AIS.Although China participants had more AIS due to large artery occlusion,were treated later and had differing ancillary management,there was no significant difference in 90-day modified Rankin scale scores 2–6(55.6% vs 47.8%;OR,adjusted for baseline and management factors 0.87(95%CI 0.71 to 1.07;p=0.20))and risk of sICH(Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria:1.4% vs 1.8%;p=0.12)compared with non-China participants.There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants.Conclusion Patients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic,clinical and management factors to patients with AIS in other regions.

No benefit of flat head positioning in early moderate-severe acute ischaemic stroke: a HeadPoST study subgroup analysis

background Although the Head Positioning in acute Stroke Trial(HeadPoST)showed no effect of the flat head position(FP;vs sitting up head position(SUP))on functional outcome,we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke(AIS)of at least moderate severity.Methods Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale(NIHSS)scores≥7,≥10 and≥14,randomised to FP or SUP<4.5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale(mRS)and death/disability(mRS scores 3-6),and any cardiovascular serious adverse event.Logistic regression analyses were undertaken adjusted for study design and baseline risk factors.results There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores:adjusted OR and 95%CI for ordinal shift and binary(3-6)mRS scores:for NIHSS≥7(n=867)0.92(0.67 to 1.25)and 0.74(0.52 to 1.04);NIHSS≥10(n=606)0.80(0.58 to 1.10)and 0.77(0.49 to 1.19);NIHSS≥14(n=378)0.82(0.54 to 1.24)and 1.22(0.69 to 2.14).Conclusions Early FP had no significant effect in patients with moderate-severe AIS.

Blood Pressure Lowering for the Secondary Prevention of Stroke

Hypertension is one of the most important modifiable risk factors for stroke,and greater than 50%of all stroke events are estimated to be attributable to elevated blood pressure(BP).Randomized trials and meta-analyses have demonstrated that reducing BP is the most effective and generalizable strategy for preventing recurrent stroke.Based on currently available evidence,BP should be reduced to below 140/90 mmHg in all patients during the chronic post-stroke phase and to below 130/80 mmHg when welltolerated.