- 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.
- 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.
- 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."
- 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.