Key result
Darapladib did not improve cognitive performance (mean MoCA score 25.3 vs 25.4; P=0.27) or reduce mild cognitive impairment (OR 1.00; 95% CI 0.93-1.09) compared to placebo in stable CHD.
Why the study?
Vascular risk factors are linked to cognitive performance differences in epidemiological studies, but evidence in patients with coronary heart disease is limited.
Does darapladib improve cognitive function in patients with stable coronary heart disease?
RCT (n=10,634)
Yes
Does darapladib improve cognitive function in patients with stable coronary heart disease?
Odds Ratio: 1 (95% CI 0.93–1.09)
In patients with stable coronary heart disease, cognitive performance is associated with modifiable cardiovascular risk factors and education, but is not influenced by darapladib.
Darapladib shows no cognitive benefit in stable CHD; leaves open whether Lp-PLA2 inhibition or risk-factor modification alters decline.
Background Vascular risk factors have been associated with differences in cognitive performance in epidemiological studies, but evidence in patients with coronary heart disease is more limited. Methods and Results The Montreal Cognitive Assessment score obtained 3.2±0.37 years after randomization to darapladib, a reversible inhibitor of lipoprotein phospholipase A 2 or placebo was evaluated for 10 634 patients with coronary heart disease from 38 countries in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. The Montreal Cognitive Assessment scores for darapladib and placebo groups were similar (mean± SD , 25.3±3.84 versus 25.4±3.73, respectively; P =0.27) and the adjusted odds ratio ( OR ) for mild cognitive impairment (Montreal Cognitive Assessment score <26) was 1.00 (95% CI , 0.93–1.09). Mild cognitive impairment was more likely with increasing age ( OR , 1.33 [1.27–1.41], +5 years after 65). For other baseline clinical characteristics, the strongest independent predictors of cognitive impairment were education (≤8 years versus college/university, OR , 2.95 [2.60–3.35]; >8 years/trade school versus college/university, OR , 1.38 [1.25–1.52] and geographic grouping). Cardiovascular risk factors independently associated with cognitive impairment were history of stroke ( OR , 1.43 [1.20–1.71]); <2.5 hours of moderate or vigorous intensity exercise/week ( OR , 1.19 [1.04–1.37]); high‐density lipoprotein cholesterol <1.16 mmol/L ( OR , 1.19 [1.04–1.37]); diabetes mellitus requiring treatment ( OR , yes versus no: 1.15 [1.05–1.26]); and history of hypertension ( OR , 1.12 [1.02–1.23]). Conclusions In patients with stable coronary heart disease, cognitive performance was associated with modifiable cardiovascular risk factors, educational level, and global region, but was not influenced by darapladib. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00799903.
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Stewart et al. (2019) conducted an RCT in stable coronary heart disease (n=10,634). darapladib vs. placebo was evaluated on mild cognitive impairment (Montreal Cognitive Assessment score <26) (OR 1.00, 95% CI 0.93-1.09). Darapladib did not improve cognitive performance (mean MoCA score 25.3 vs 25.4; P=0.27) or reduce mild cognitive impairment (OR 1.00; 95% CI 0.93-1.09) compared to placebo in stable CHD.
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