Interaction of brain imaging features and effects of intensive blood pressure lowering after endovascular treatment for acute ischaemic stroke: the pre-specified secondary analyses of ENCHANTED2/MT trial.

Background: The second Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED2/MT) was terminated early when the intensive blood pressure lowering to a systolic level of 120 mm Hg or lower, compared to 140-180 mm Hg, was harmful in patients who received successful endovascular therapy for acute ischaemic stroke due to large-vessel occlusion. We aimed to determine the interaction of key brain imaging features and the effect of treatment on clinical outcomes.

Methods: ENCHANTED2/MT was a prospective, randomised, open-label, blinded-endpoint, controlled trial that aimed to assess the effectiveness of different intensities of blood pressure control on the functional independence in patients who had received successful endovascular therapy for acute ischaemic stroke from large-vessel occlusion at 44 hospitals in China between July 20, 2020 and March 7, 2022. In these pre-specified secondary analyses, neuroradiologists reviewed the baseline brain images of participants (computerised tomography [CT], CT with angiography [CTA] and digital subtraction angiography [DSA]) blind to treatment allocation, to determine the degree of cerebral infarction on the Alberta Stroke Program Early CT Score (ASPECTS), collateral status according to modified TAN score, and degree of reperfusion on the expanded Treatment In Cerebral Infarction (eTICI) scale. The primary outcome was functional independence, according to the distribution of scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Multivariable logistic regression analysis was done according to the modified intention-to-treat principle in all participants with available outcome data. ENCHANTED2/MT is registered with ClinicalTrials.gov, NCT04140110.

Findings: Of 816 participants in the trial, in whom 407 were assigned to more intensive blood pressure lowering and 409 were assigned to less intensive blood pressure lowering treatment, there were 533, 372, and 757 participants with available data for ASPECTS, collateral flow, and eTICI analyses, respectively. Intensive blood pressure lowering was associated with worse functional independence in participants with complete reperfusion (eTICI 3: adjusted odds ratio [aOR] 1.51, 95% CI 1.14-2.02) but not in those with incomplete reperfusion (eTICI 2b/c: aOR 1.29, 95% CI 0.73-2.28), without significant interaction (p_interaction = 0.82). There was no significant interaction between blood pressure treatment and ASPECTS (0-5 vs. 6-10: aOR 1.27, 95% CI 0.77-2.11 vs. aOR 1.37, 95% CI 0.91-2.07; p_interaction = 0.14) on functional independence. However, more intensive blood pressure lowering treatment was associated with worse functional independence in participants with poor collateral status (aOR 1.99, 95% CI 1.11-3.57) compared to those with good collateral status (aOR 0.87, 95% CI 0.53-1.45), with a moderate level of interaction (p_interaction = 0.037).

Interpretation: Our study indicates that collateral status may help identify patients at risk from intensive blood pressure lowering treatment to a systolic target of 120 mm Hg or lower, in patients undergoing endovascular therapy for acute ischaemic stroke from large-vessel occlusion.

Funding: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Foundation (MRF) of the UK; AstraZeneca; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.