Intensive versus guideline‐recommended blood pressure reduction in acute lacunar stroke with intravenous thrombolysis therapy: The ENCHANTED trial

Abstract

Background and purpose This was an investigation of the differential effects of early intensive versus guideline‐recommended blood pressure (BP) lowering between lacunar and non‐lacunar acute ischaemic stroke (AIS) in the BP arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods In 1,632 participants classified as having definite or probable lacunar (n = 454 [27.8%]) or non‐lacunar AIS according to pre‐specified definitions based upon clinical and adjudicated imaging findings, mean BP changes over days 0–7 were plotted, and systolic BP differences by treatment between subgroups were estimated in generalized linear models. Logistic regression models were used to estimate the BP treatment effects on 90‐day outcomes (primary, an ordinal shift of modified Rankin scale scores) across lacunar and non‐lacunar AIS after adjustment for baseline covariables. Results Most baseline characteristics, acute BP and other management differed between lacunar and non‐lacunar AIS, but mean systolic BP differences by treatment were comparable at each time point (all pinteraction > 0.12) and over 24 h post‐randomization (−5.5, 95% CI −6.5, −4.4 mmHg in lacunar AIS vs. −5.6, 95% CI −6.3, −4.8 mmHg in non‐lacunar AIS, pinteraction = 0.93). The neutral effect of intensive BP lowering on functional outcome and the beneficial effect on intracranial haemorrhage were similar for the two subgroups (all pinteraction > 0.19). Conclusions There were no differences in the treatment effect of early intensive versus guideline‐recommended BP lowering across lacunar and non‐lacunar AIS.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage

“…The ENCHANTED trial observed no significant heterogeneity of the treatment effect (shift on 3-month mRS score) in subgroups including demographics (age, sex, ethnicity), pre-treatment with antiplatelets, dose of alteplase (low vs. standard), stroke severity stratified by NIHSS scores and stroke subgroups where large vessel occlusion might be anticipated, AIS subtypes classified on the basis of clinician diagnosis of large vessel atherosclerosis, cardioembolism or lacunar stroke. 80,82 Notably, in the prespecified subgroup analysis of severe stroke defined by computed tomography or magnetic resonance angiogram confirmation of large vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atherosclerotic disease, or high (>10) baseline NIHSS score there was no significant difference in the primary outcome of death or disability at three months in the two treatment arms. However, intensive blood pressure lowering significantly increased threemonth mortality (OR 1.52, 95%CI: 1.09-2.13; p ¼ 0.014) compared with guideline blood pressure lowering, despite significantly lower clinicianreported ICH (OR0.63, 95%CI: 0.43-0.92; p ¼ 0.016).…”

The Potential Impact of Neuroimaging and Translational Research on the Clinical Management of Lacunar Stroke

“…The potentially harmful effect of intensive blood lowering could also be more relevant in the hyperacute phase for the potential decrease in residual compensatory perfusion flow that could accelerate the ischemic process. However, a substudy of the enhanced control of hypertension and thrombolysis stroke study (ENCHANTED) did not suggest any deleterious effect of acute blood pressure lowering, as the functional outcome in patients with lacunar stroke treated with thrombolysis was similar, independently of standard (blood pressure < 185/110 mmHg) vs. intensive (systolic target 130-140 mmHg) within one hour from randomization [191].…”

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

“…16 Our results suggest greater END after thrombolysis for LVO participants allocated to intensive BP lowering treatment, but the play of chance cannot be excluded in relation to the small subset of participants in these particular analyses. However, our recent post-hoc analysis with larger samples (N ¼ 1311) that included ENCHANTED BP arm participants with severe AIS (defined by the combination of LVO and baseline NIHSS score > 10), 17 as well as another analysis in participants with definite non-lacunar AIS (N ¼ 784), 18 both showed an increased risk of death in those who were allocated to intensive BP lowering, which adds to the concern of large BP falls in these types of AIS patients.…”