Predictors of recurrent stroke among patients with lacunar stroke receiving intensive blood pressure control: a secondary analysis of the secondary prevention of small subcortical strokes trial.

BACKGROUND

Intensive systolic blood pressure (SBP) lowering to <130 mm Hg is recommended in contemporary secondary stroke prevention guidelines; however, it did not significantly reduce overall recurrent ischemic stroke in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. In this post hoc secondary analysis of participant-level SPS3 trial data, we sought to identify baseline predictors of recurrent ischemic stroke among patients with lacunar stroke assigned to the lower SBP target in SPS3.

METHODS

This post hoc secondary analysis included SPS3 participants randomized to the lower SBP target (<130 mm Hg). The primary outcome was centrally adjudicated recurrent ischemic or hemorrhagic stroke. Candidate predictors were evaluated with multivariable Cox proportional hazards regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS

Among 1501 participants (41.1% aged ≥ 65 years; 60.8% were men), 120 (8.0%) experienced recurrent ischemic stroke over a median follow-up of 3.49 years (interquartile range, 1.80-5.08), corresponding to an incidence rate of 2.43 events per 100 person-years. In unadjusted comparisons, recurrent ischemic stroke was associated with diabetes mellitus (44.2% vs 34.2%; p = .036), coronary artery bypass grafting/coronary stent (9.2% vs 4.1%; p = .018), Black race (24.2% vs 14.4%; p = .007), elevated serum creatinine (14.2% vs 7.7%; p = .022), aspirin or clopidogrel use at the qualifying lacunar stroke (44.2% vs 28.5%; p < .001), large-vessel atherosclerosis (29.3% vs 17.9%; p = .004), and lower prevalence of a subcortical qualifying stroke (21.7% vs 46.1%; p < .001). In multivariable analysis, aspirin or clopidogrel use at the qualifying lacunar stroke (HR, 1.69; 95% CI, 1.14-2.50; p = .009) and large-vessel atherosclerosis (HR, 1.63; 95% CI, 1.08-2.413; p = .020) were independently associated with recurrence. Randomization to aspirin plus clopidogrel was not associated with recurrent ischemic stroke (HR, 1.09; 95% CI, 0.75-1.57; p = .661).

CONCLUSIONS

In SPS3 participants assigned to intensive SBP control, 8.0% experienced recurrent ischemic stroke. Aspirin or clopidogrel use at the qualifying lacunar stroke and large-vessel atherosclerosis remained independent predictors of recurrence. These findings may help identify patients who require preventive strategies beyond intensive SBP lowering.