• Dementias
• Cerebrovascular Disease
• Neurology

• Dementias
• Cerebrovascular Disease
• Neurology

Neither aggressive blood pressure (BP) lowering nor dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced the rate of cognitive decline after a lacunar stroke, said Oscar R. Benavente, MD, University of British Columbia, Vancouver, British Columbia, Canada, who presented the results for this secondary outcome from the Secondary Prevention of Small Subcortical Strokes Trial [SPS3; NCT00059306].

In the international, multicenter SPS3 study, patients with a lacunar stroke, as verified by magnetic resonance imaging, were randomized in a 2×2 factorial design to a lower systolic BP (SBP; <130 mm Hg; n=501) or higher SBP target (130 to 149 mm Hg; n=1519) and to clopidogrel 75 mg or placebo. All patients received aspirin 325 mg daily. BP management was open label. The median time to randomization from the index event was 62 days.

The lower BP target was associated with a nonsignificant reduction in the primary endpoint of all strokes (HR, 0.81; 95% CI, 0.64 to 1.03; p=0.08) and disabling and fatal strokes (HR, 0.81; 95% CI, 0.53 to 1.23; p=0.32), as well as a significant reduction in intracerebral hemorrhage (HR, 0.37; 95% CI, 0.15 to 0.95; p=0.03) [The SPS3 Study Group. Lancet 2013].

At study entry, the BP levels in the lower and higher target groups, respectively, were 144/78 mm Hg and 145/80 mm Hg. At 1 year, the difference in SBP between the groups was 11 mm Hg (127 and 138 mm Hg, respectively) and was maintained to study end. The mean Mini-Mental State Examination (MMSE) was 28 and the mRS score was 66% to 67%. The mean age of the patients was 63 years.

Cognitive assessments were conducted at study entry and annually thereafter by blinded, certified examiners using eight tests covering most cognitive domains. However, the cognitive abilities screening instrument (CASI) was the main test used to determine the benefit of the study interventions. Scores were normalized using published norms for age, sex, education, and region. Linear mixed models were fit to determine whether changes over time differed by BP group. Importantly, cognitive testing results after a recurrent stroke were excluded.

In this analysis, 2916 patients with a baseline assessment were included, with nearly 11,000 total assessments. On average, there were 3.3 assessments per patient, with a range of 1 to 9 assessments.

The overall mean CASI z-scores ranged from −0.59 at study entry to −0.39 at Year 5 to 1.11 at Year 8. The average change in the CASI z-score from study entry to Year 1 was 0.11 (SD=0.84) and from study entry to Year 3 was 0.15 (SD=0.97). This modest decrease in the z-score was not significant, said Prof. Benavente. No interaction was seen between BP treatment (p=0.30) or DAPT (p=0.95), and CASI z-score, even after adjustment. No interaction was seen for the four interventions and CASI z-score (p=0.26).

In this cohort of lacunar stroke patients, a modest nonsignificant decline in cognitive function was observed over the first year. Concluding that neither intervention modified the rate of cognitive decline, Prof. Benavente stated the age and mean MMSE of the cohort and the mean follow-up of only 3.6 years must be considered.

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