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Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment
Ashkan Shoamanesh1, Lesly A Pearce2, Carlos Bazan3
1McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada.
Objective:
To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment.
Methods:
SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection.
Results:
CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments.
Interpretation:
Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207.
Insights
Cerebral microbleeds (CMBs) are common in lacunar stroke patients and significantly increase the risk of recurrent stroke. These findings suggest CMBs indicate advanced small vessel disease requiring targeted therapies.
Area of Science:
- Neurology
- Radiology
- Cardiovascular Research
Background:
- Lacunar strokes are often associated with cerebral small vessel disease.
- Cerebral microbleeds (CMBs) are a marker of small vessel disease, but their prognostic significance in lacunar stroke is not fully understood.
Purpose of the Study:
- To characterize cerebral microbleeds (CMBs) in patients with lacunar stroke within the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.
- To assess the relationship between CMBs and recurrent stroke, death, and treatment response.
Main Methods:
- Analysis of 1,278 participants from the SPS3 randomized clinical trial.
- Baseline MRI (T2*-weighted gradient echo sequence) was used for CMB detection.
- Patients were randomized to different blood pressure targets and antiplatelet therapies.
Main Results:
- CMBs were present in 30% of patients.
- Independent predictors of CMBs included male gender, hypertension history, higher systolic blood pressure, nondiabetic status, multiple old lacunar infarcts, and white matter hyperintensities.
- Patients with CMBs had a 2-fold increased risk of recurrent stroke (adjusted hazard ratio = 2.1).
- CMBs were not associated with an increased risk of death.
Conclusions:
- Cerebral microbleeds in lacunar stroke patients suggest a more advanced stage of cerebral small vessel disease.
- These patients may benefit from more aggressive or targeted therapeutic strategies.
- No significant interactions were found between CMBs and the assigned treatments in the SPS3 trial.
