Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial

Kailash Krishnan,Robert A Dineen,Nikola Sprigg,Stephen J Phillips,John Gommans,Joanna M Wardlaw,Christopher Chen,Alessandro Adami,Panos Koumellis,Polly Scutt,Kennedy R Lees,Ana M Casado,George Ntaios,Anna Członkowska ,Rónán Collins ,Lisa J Woodhouse ,L.a Cala ,Şerefnur Öztürk ,Szabolcs Szatmári ,Hanne Christensen ,Jennifer Becker ,Philip M Bath

doi:10.1016/j.jstrokecerebrovasdis.2016.01.010

Abstract

Background and purposeMore than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.MethodsENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life.ResultsBlood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events.ConclusionsAmong patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.

Highlights

There were no significant differences between the 2 groups at day 90 in any of the secondary clinical outcomes (Table 3) or death (Fig S3), or serious adverse rates (Table S1). In this preplanned subgroup analysis of patients in Efficacy of Nitric Oxide in Stroke (ENOS) with acute intracerebral hemorrhage (ICH), there was no difference in the primary outcome of function between patients randomized to 7 days of continuing versus stopping prestroke antihypertensive therapy[17]; this finding was consistent across all prespecified subgroups of patients
There were no differences in safety outcomes or secondary outcome measures at day 90
The overall neutral results seen for the continue versus stop comparison in ENOS16 are similar to those seen in the smaller Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) trial.[14]

Summary

Introduction

Lowering BP long term after stroke is key for secondary prevention,[8] it remains unclear whether prestroke antihypertensive drugs should be continued or stopped temporarily during the acute phase.[9] Arguments both for and against each strategy can be postulated and guidelines lack firm recommendations related to this subject.[10,11] Continuing prior antihypertensive drugs after ICH might limit hematoma expansion, reduce the development of cerebral edema and early recurrence, and improve longterm outcome.[8,12] And yet, continuing treatment may lead to the development of hypotension, thereby compromising regional cerebral perfusion because of dysfunctional cerebral autoregulation.[13] Further, continuing treatment involves administering tablets at a time when many patients have dysphagia and limited enteral access, a risk for aspiration pneumonia. Antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.

Methods

Results

Conclusion