Effect of treatment delay, stroke type, and thrombolysis on the effect of glyceryl trinitrate, a nitric oxide donor, on outcome after acute stroke: a systematic review and meta-analysis of individual patient from randomised trials

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke

Management of blood pressure in acute stroke

The importance of elevated or low arterial blood pressure (BP) early after stroke, and the need for pharmacological intervention to control BP, remains controversial. Debate surrounds if, when and how to intervene. This debate is informed by conflicting results from observational data and underpowered clinical trials and substantive outcome data are lacking. Accordingly, management decisions have largely been left up to the individual treating physician and guidelines are based on ‘good practice’ and theory rather than level 1, grade A evidence. Substantial progress has been made in recent years, particularly in the field of hemorrhagic stroke, where recently presented and soon to completed large-scale trials may finally give us a firm evidence base. For ischemic stroke, many important studies have informed our understanding of the basic pathophysiology, epidemiology, treatment and outcomes of BP management in acute stroke and, although not yet constituting a solid ‘evidence base’, are helping us from the ‘cognitive quick-sand’ of small studies and personal experiences