Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

Abstract

Background It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke.Methods We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression.Findings Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01−2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24−3.79). Other outcomes (disability -Barthel Index, quality of life -EQ-visual analogue scale, cognition -telephone mini-mental state examination, and mood -Zung depression scale) were also worse with continuing treatment.Interpretation In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse

European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease

“…46,47 A recent post-hoc analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) trial indicated a shift toward a worse outcome measured by the modified Rankin Scale by day 90 (OR 1.46, 95% CI 1.01–2.11). 48 In a more recent trial of patients treated with intravenous thrombolysis comparing intensive versus standard blood pressure lowering treatment did not show a significant difference in the effect on death or disability at 90 days, but did show increased mortality caused by intensive blood pressure lowering treatment (OR 1.52, 95% CI 1.09–2.13). 49 All of the trials included patients regardless of the atherosclerosis status of the intracranial arteries.…”