Intravenous thrombolysis in patients with acute ischemic stroke and cerebral microbleeds: Results from the ENCHANTED trial

Objective: To determine associations between cerebral microbleeds (CMBs) and intracerebral hemorrhage (ICH) as well as functional recovery after thrombolysis in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: ENCHANTED recruited acute ischemic stroke (AIS) patients eligible for thrombolytic therapy from 111 clinical centers in 13 countries. We included those with T2*-weighted or susceptibility-weighted brain magnetic resonance imaging within 6 h after AIS. Associations between CMB (primary predictor), burden (0, 1, 2-4, or ⩾5 CMBs), and location (deep, lobar, mixed) and any ICH (primary outcome), symptomatic intracerebral hemorrhage (sICH), 90-day disability or death (modified Rankin scale (mRS) score 2-6), and other unfavorable functional outcomes (mRS 3-6, 6, and shift) were explored in logistic regression models and in a stratification by alteplase dose.

Results: Of 311 eligible AIS participants, 111 (35.7%) had CMB(s) and this was not associated with an increase in any ICH (adjusted odds ratio = 1.49, 95% confidence interval (CI) = 0.87-2.54) or sICH (2.05, 0.92-4.56). However, the presence of CMB(s) was associated with 90-day disability or death (1.75, 1.04-2.94) and other unfavorable functional outcomes. Comparable associations were seen between CMB burden (defined as ordinally categorical; any ICH 1.16 (0.90-1.50), mRS 2-6 1.44 (1.11-1.87)) or mixed deep-lobar distribution (any ICH 1.42 (0.61-3.29), mRS 2-6 3.66 (1.48-9.05)) and these outcomes. There were no differences in associations between CMB presence/burden/distribution and outcomes between two different alteplase doses ( P interaction  > 0.087).

Conclusion: In ENCHANTED, CMB(s) was associated with 90-day unfavorable function recovery but not with a significantly increased likelihood of ICH in post-intravenous thrombolytic AIS. Low-dose alteplase may not offer a better profile for AIS with CMB(s). 

Data access statement: Individual de-identified participant data used in this analysis will be shared by request from any qualified investigator via the Research Office of The George Institute for Global Health.