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Abstract
Objective To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.
Methods The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.
Results Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was −0.91 (95% confidence interval [CI] −2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, −0.54 (95% CI −1.88 to 0.80) for rosuvastatin compared with placebo, and −1.43 (95% CI −3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.
Conclusions Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.
ClinicalTrials.gov identifier NCT00468923.
Classification of evidence This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.
Glossary
- ADL=
- activities of daily living;
- ANCOVA=
- analysis of covariance;
- BP=
- blood pressure;
- CI=
- confidence interval;
- CVD=
- cardiovascular disease;
- DSST=
- Digit Symbol Substitution Test;
- EQ-5D=
- EuroQol 5D;
- HOPE-3=
- Heart Outcomes Prevention Evaluation-3;
- LDL=
- low-density lipoprotein;
- LDL-C=
- low-density lipoprotein cholesterol;
- MIND=
- Memory and Cognition in Decreased Hypertension;
- mMoCA=
- modified 12-item Montreal Cognitive Assessment;
- OR=
- odds ratio;
- PRoFESS=
- Prevention Regimen for Effectively Avoiding Second Strokes;
- SAGE=
- Standard Assessment of Global Activities in the Elderly;
- SBP=
- systolic blood pressure;
- SPRINT=
- Systolic Blood Pressure Intervention Trial;
- SPS3=
- Secondary Prevention of Small Subcortical Strokes Trial;
- TMT-B=
- Trail Making Test Part B
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed at links.lww.com/WNL/A01.
Editorial, page 593
Class of Evidence: NPub.org/coe
- Received October 9, 2017.
- Accepted in final form November 15, 2018.
- © 2019 American Academy of Neurology
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