No cognitive benefit from BP, lipid lowering in HOPE-3

  • Neurology

  • curated by Susan London
  • Clinical Essentials
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  • Older adults at intermediate cardiovascular risk do not have better cognition if treated long term with candesartan plus hydrochlorothiazide (Atacand HCT), rosuvastatin (Crestor), or their combination.

Why this matters

  • High prevalence and toll of cognitive impairment and dementia in the geriatric population.

Key results

  • Compared with placebo:
    • Candesartan-hydrochlorothiazide (HCTZ) reduced systolic blood pressure by 6.0 mm Hg.
    • Rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL.
  • With median 5.7-year follow-up, mean difference in change in Digit Symbol Substitution Test scores vs placebos:
    • −0.91 (95% CI, −2.25 to 0.42) for candesartan-HCTZ.
    • −0.54 (95% CI, −1.88 to 0.80) for rosuvastatin.
    • −1.43 (95% CI, −3.37 to 0.50) for combination.
  • No significant differences in modified Montreal Cognitive Assessment, TrailMaking Test Part B.

Expert comment

  • In an editorial, Christopher Chen, MD, and Craig S. Anderson, MD, PhD, write, "Big data analytics of diverse populations, differing treatment approaches, longer duration of follow-up, and statistical approaches to adjust for confounding might overcome the inherent limitations of randomized controlled trials. Even delaying the onset of dementia by a year could accomplish immense public health improvement."

Study design

  • Randomized controlled trial with 2 by 2 factorial design having 2361 adults aged ≥70 years without known cardiovascular disease or need for treatment, but with ≥1 additional cardiovascular risk factors (HOPE-3 trial).
  • Randomization: double-blind candesartan (16 mg)+HCTZ (12.5 mg) vs placebo, and rosuvastatin (10 mg) vs placebo.
  • Main outcome: cognitive function.
  • Funding: Canadian Institutes of Health Research; AstraZeneca.


  • Missing outcome data for ~25% of participants.
  • Final assessment often done by telephone.
  • Possibility that follow-up not long enough.