Welcome to the WSC 2022 Interactive Program

Background and Aims

Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of stroke, cardiovascular disease (CVD) and CVD mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV).

Methods

Measurements of brachial-ankle or carotid-femoral pulse wave velocity (baPWV or cfPWV) were obtained by a literature search either as individual participant or summary data, mostly from community-based observational studies. Age trajectories of PWV were estimated using mixed-effects meta-regression and generalized additive models for location, scale, and shape.

Results

This meta-analysis included 167 studies in 509743 subjects from 34 countries. PWV depended non-linearly on age, sex, and country. Global age-standardised averages were 12·5 m/s for baPWV and 7·45 m/s for cfPWV. Males had higher global levels than females of 0·77 m/s for baPWV and 0·35 m/s for cfPWV, but sex differences in baPWV diminished with age. In Asia, baPWV was substantially higher than in Europe (+1·83 m/s), whereas cfPWV was higher in Africa than in Europe (+0·41 m/s) and differed more strongly by country. High country income was associated with lower baPWV (0·55 m/s) and cfPWV (0·41 m/s).

Conclusions

High PWV in Asia, associated with high central blood and pulse pressure, may partly explain Asian high risk for intracerebral haemorrhage and small vessel stroke. Reference values provided may facilitate use of PWV as a marker of vascular ageing, for prediction of vascular risk and death, and in future therapeutic interventions.

Background and Aims

In patients with intracerebral hemorrhage (ICH) the presence of intraventricular hemorrhage (IVH) constitutes an important therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes.

Methods

This individual participant data(IPD) meta-analysis pooled 1,501 patients from two randomized trials and seven observational studies enrolled during 2004 to 2015. We compared IVF vs standard of care(SoC, including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH and/or IVH. The primary outcome was functional disability evaluated by the modified Rankin Scale(mRS, range:0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS:0-3 vs mRS:4-6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random-effects- and doubly-robust-models to calculate odds-ratios(OR) and absolute treatment-effects(ATE).

Results

Comparing treatment of 596 with IVF to 905 with SoC resulted in an ATE to achieve the primary outcome of 9.3%[95%CI4.4-14.1]. IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common-OR:1.75[95%CI1.39-2.17], reduced mortality, OR:0.47[95%CI 0.35-0.64], without increased adverse events, absolute difference:1.0%[95%CI-2.7-4.8]. Exploratory analyses provided that early IVF-treatment(≤48 hours) after symptom onset was associated with an ATE:15.2%[95%CI8.6-21.8] to achieve the primary outcome.

Conclusions

As compared to SoC, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage significantly improved functional outcome at 6 months. The treatment effect was linked to an early time-window<48h, specifying a target population for future trials.

Background and Aims

Sovateltide (Tycamzzi™) in animal models of acute cerebral ischemic stroke (ACIS) increased cerebral blood flow, had anti-apoptotic activity, and produced neurovascular remodeling when administered intravenously. In addition, it was safe and well-tolerated in healthy human volunteers, and it improved neurological outcomes in patients with ACIS 90 days post-treatment (NCT04046484).

Methods

A phase III study fully enrolled 158 patients with ACIS, of which 138 completed 90-day follow-up. All patients received standard treatment and were randomly assigned to either control (saline; n=70) or sovateltide cohort (n=68). The inclusion and exclusion criteria are at NCT04047563. Clinical outcome parameters NIHSS and mRS for ACIS were determined. Standard treatment and care were provided to all the patients. Sovateltide or normal saline was administered in three doses, each 0.3 μg/kg, as an intravenous bolus over 1 min at an interval of 3 ± 1 h on day 1, day 3, and day 6 post-randomization.

Results

Patient demographics and baseline characteristics were comparable between the two groups, including baseline NIHSS (saline 10.82 ± 0.41; sovateltide 9.79 ± 0.34) scores. The number of patients having a reduction of 2 or more in mRS was 52.86% in control and 72.06% in the sovateltide group (p=0.0199). mRS in the group treated with sovateltide compared to the comparator group at 90 days after treatment was significantly lower (p=0.0081). NIHSS showed similar improvement in the sovateltide group (p=0.0028) compared to the control group at 90 days of treatment.

Conclusions

Sovateltide significantly improved neurological outcomes in patients with acute cerebral ischemic stroke.

Background and Aims

Methods

Results

Conclusions