Cognitive decline in older adults appears to be unaffected by the use of candesartan plus hydrochlorothiazide, rosuvastatin, or a combination of these medications, according to an article recently published in Neurology.
The placebo-controlled, double-blind, randomized Heart Outcomes Prevention Evaluation-3 study included 2361 participants (mean age, 74.1±3.5 years) from 21 different countries. Participants had no known cases of cardiovascular disease and all completed baseline and end-of-study assessments using the modified Montreal Cognitive Assessment, Trail Making Test Part B, and Digit Symbol Substitution Test. They were randomly assigned to receive candesartan 16 mg plus hydrochlorothiazide 12.5 mg or placebo, or rosuvastatin 10 mg or placebo.
The candesartan plus hydrochlorothiazide combination was associated with a 6.0 mm Hg reduction in systolic blood pressure compared with placebo, whereas rosuvastatin was associated with a 24.8 mg/dL reduction in low-density lipoprotein cholesterol. Of the total study population, 1626 participants finished assessments both at baseline and at end of study, after a median 5.7-year follow-up. Hypertension was present in 45% of participants. Compared with the placebo group, the mean change in Digit Symbol Substitution Test scores was -0.91 (95% CI, -2.25 to 0.42) with candesartan plus hydrochlorothiazide, -0.54 (95% CI, -1.88 to 0.80) with rosuvastatin, and -1.43 (95% CI, -3.37 to 0.50) with combination therapy. Cognitive functional decline did not increase or decrease with these medications.
Limitations to this study include an inability to gather data at both time points due to approximately 25% of the study population dying before the end of the study, a final visit done by telephone and the associated risk of acute cognitive decline keeping participants from returning, and potential selection bias.
The study researchers concluded that “in a population ≥70 years of age at intermediate risk of [cardiovascular disease] … we observed that [blood pressure] lowering with candesartan/hydrochlorothiazide, lipid lowering with rosuvastatin, and the combination did not reduce or increase the rate of cognitive or functional decline over median follow-up of 5.7 years.”
Disclosures: This study received funding from the Canadian Institutes of Health Research and AstraZeneca. Certain authors report financial associations with pharmaceutical corporations. For a full list of author disclosures, see the reference.
Bosch J, O’Donnell M, Swaminathan B, et al. Effects of blood pressure and lipid lowering on cognition: results from the HOPE-3 study [published online February 27, 2019]. Neurology. doi: 10.1212/WNL.0000000000007174