Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study.

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. CLINICALTRIALSGOV 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.

Efeitos da pressão arterial e redução de lipídios na cognição: resultados do estudo HOPE-3 / Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study

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.(AU)

Central statistical monitoring: detecting fraud in clinical trials.

BACKGROUND: Central statistical monitoring in multicenter trials could allow trialists to identify centers with problematic data or conduct and intervene while the trial is still ongoing. Currently, there are few published models that can be used for this purpose. PURPOSE: To develop and validate a series of risk scores to identify fabricated data within a multicenter trial, to be used in central statistical monitoring. METHODS: We used a database from a multicenter trial in which data from 9 of 109 centers were documented to be fabricated. These data were used to build a series of risk scores to predict fraud at centers. All analyses were performed at the level of the center. Exploratory factor analysis was used to select from 52 possible predictors, chosen from a variety of previously published methods. The final models were selected from a total of 18 independent predictors, based on the factors identified. These models were converted to risk scores for each center. RESULTS: Five different risk scores were identified, and each had the ability to discriminate well between centers with and without fabricated data (area under the curve values ranged from 0.90 to 0.95). True- and false-positive rates are presented for each risk score to arrive at a recommended cutoff of seven or above (high risk score). We validated these risk scores, using an independent multicenter trial database that contained no data fabrication and found the occurrence of false-positive high scores to be low and comparable to the model-building data set. LIMITATIONS: These risk score have been validated only for their false-positive rate and require validation within another trial that contains centers that have fabricated data. Validation in noncardiovascular trials is also required to gage the usefulness of these risk scores in central statistical monitoring. CONCLUSIONS: With further validation, these risk scores could become part of a series of tools that provide evidence-based central statistical monitoring, which in turn can improve the efficiency of trials, and minimize the need for more expensive on-site monitoring.