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HOPE-3: Rosuvastatin, antihypertensive drugs do not prevent cognitive decline
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NEW ORLEANS — New data from the HOPE-3 study do not show any effect of rosuvastatin or BP-lowering drugs for prevention of decline in cognitive function, researchers reported at the American Heart Association Scientific Sessions.
In the main results of HOPE-3, a study of 12,705 individuals at intermediate CV risk, rosuvastatin (Crestor, AstraZeneca) was associated with a 25% reduction in CV events in the entire cohort, and a BP-lowering regimen of candesartan and hydrochlorothiazide was associated with a 24% reduction in CV events in those with hypertension.
For the cognition substudy, the researchers analyzed 1,626 participants from HOPE-3 aged 70 years and older who completed cognitive and functional questionnaires at baseline and at the end of the study (mean age, 74 years; 59% women; 24% white; 45% with hypertension), Jackie Bosch, PhD, associate professor of rehabilitation science at McMaster University and director of the prevention program at the Population Health Research Institute, Hamilton, Ontario, Canada, said during a press conference.
The primary outcome was decline in processing speed as determined by the Digit Symbol Substitution Test (DSST). Secondary outcomes included decline in executive function as assessed by the modified Montreal Cognitive Assessment (mMoCA) and increase in psychomotor speed per the Trail Making Test Part B. Median follow-up was 5.6 years.
At the end of the study, DSST scores were similar in those assigned the BP-lowering regimen vs. those assigned placebo (BP-lowering group, 29.1; placebo group, 29.4; change in means, 0.1; P = .86), in those assigned rosuvastatin vs. those assigned placebo (rosuvastatin group, 29.1; placebo group, 29.4; change in means, –0.5; P = .38) or in those assigned the BP-lowering regimen and rosuvastatin vs. those assigned double placebo (treatment group, 29.3; placebo group, 29.9; change in means, –0.4; P = .63), Bosch said.
BP-lowering and cholesterol-lowering regimens also had no effect compared with placebo on the mMoCA score measuring decline in cognitive function or the Trail Making Test Part B score measuring psychomotor speed, she said.
Results for the BP-lowering regimen vs. placebo were consistent by age (P for trend = .97) and there was a signal that the effect was greater in those with higher systolic BP at baseline (P for trend = .078), while results for rosuvastatin vs. placebo were consistent by age (P for trend = .8) and there was a signal that the effect was greater in those with higher LDL at baseline (P for trend = .11), according to Bosch.
“What we see is a visual trend for increased cognitive decline at the lowest tertile of systolic BP, and a slight benefit for those at the highest [tertile],” Bosch said at the press conference. “In the rosuvastatin vs. placebo comparison … if we look to the tertiles of LDL at baseline, we see no effect in the lowest and middle tertiles, but in the highest tertile, there is a visual indication that something might be happening.”
Those findings raise the question of “whether there could have been an effective combination therapy for those with high systolic BP and high LDL at baseline,” she said. Among those in the highest tertiles of BP and LDL, those who received both the BP and statin regimens had less of a decline in the primary outcome than those who received double placebo (P = .04), she said.
In a post hoc analysis, the researchers found that among patients followed longer than 5.5 years, the BP regimen had a positive effect on the primary outcome (P for trend = .036), but there was no similar trend for rosuvastatin, she said.
The groups also did not differ in new functional impairment or any functional impairment at the end of the study, according to the researchers.
In a discussant presentation during the press conference, Ralph L. Sacco, MD, chairman of the department of neurology at University of Miami Miller School of Medicine and past president of the AHA, said there is a “silver lining” to the data even though they didn’t show a significant impact on cognitive function.
“Statins did not worsen cognition, and as Dr. Bosch mentioned, that had been a concern,” he said. “Also, in some of the subgroups, for those who had the highest risk … [the interventions] showed some benefit. It may be that because this was a lower-risk population, it was insensitive to finding definitive outcomes. … We probably need to be treating higher-risk patients, treating them at younger ages and treating them for longer periods.” – by Erik Swain
Reference:
Bosch J, et al. LBCT.01 – Big Trials for Big Questions. Presented at: American Heart Association Scientific Sessions; Nov. 12-16, 2016; New Orleans.
Disclosure: The trial was funded by AstraZeneca and the Canadian Institutes of Health Research. Bosch and Sacco report no relevant financial disclosures.
Perspective
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Leslie Cho, MD
This rigorous study showed no benefit of controlling BP or high cholesterol on cognitive function. The problem with the study is that it looked at patients over the age of 70 years and it only followed them for about 5.5 years. There were some followed for longer than that. By the time you get to 70, it might be too late for such an intervention. The best way to do these studies would be to study individuals earlier on and follow them for a longer time to see if there is a true cognitive benefit for control of high BP and cholesterol.
There’s a trend toward benefit if you treat people with very high cholesterol to improve their cognitive function, but that’s from a post hoc analysis. We know from other studies that it’s people who have hypertension in midlife that go on to have dementia and cognitive decline. If you want to have a study on that topic, it should start midlife and follow participants for a longer duration.
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