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NEW ORLEANS -- A large substudy of the HOPE-3 trial found no benefit relating to cognitive function in patients who took cholesterol or blood pressure-lowering drugs.
In recent years cognitive decline and dementia have emerged as a concern equal if not even greater than cardiovascular disease in aging people. Hypertension has been linked to cognitive decline while some have suggested that statins may lead to memory problems.
The main HOPE-3 study, reported in April at the American College of Cardiology meeting and published in the New England Journal of Medicine, found that in a primary prevention setting statin therapy with rosuvastatin lowered cardiovascular events significantly but antihypertensive therapy did not have a significant effect.
A HOPE-3 substudy, presented by Jackie Bosch, PhD, of McMaster University, at the American Heart Association meeting in New Orleans, examined the effect of the study drugs on cognitive and functional decline in 1,626 patients over more than 5 years of followup.
There were no significant differences in any of cognitive and functional outcome measures in the study. However, there was a trend toward improvement in a post hoc analysis that looked at the small number of patients (n=93) who at baseline were in the highest tertile of blood pressure (over 145 mm Hg) and LDL (over 140 mg dL).
One potentially important finding of the study is that there was no evidence of any sort for cognitive decline in patients taking rosuvastatin. This, Bosch said in an interview, helps refute earlier anecdotal and observational studies that raised concerns about the cognitive effects of statins. She said she supported removing the black box warning about cognitive effects on statin labels.
Sverre Kjeldsen, MD, PhD, of Oslo University Hospital, said that this study does not end all "hope" that blood pressure reduction may help prevent cognitive decline. He pointed out that baseline blood pressure levels in HOPE-3 were not very high to begin with (138/82 mm Hg). "If we want to prevent cognitive decline by treating high blood pressure, blood pressure must be clearly elevated. It is great that the HOPE-3 investigators are trying, but HOPE-3 is not really a hypertension study. People may need to have higher blood pressure and maybe long-lasting hypertension, and the trial intervention may need to continue for a longer period of time."
Kjeldsen also said that he "deeply regrets that we never investigated cognitive function in all the hypertension trials that we did over the years, but when we planned and initiated these trials in the early and late 1990's we were not aware of the situation, although we should have been."
Franz Messerli, MD, of Mount Sinai, said that there have been several studies that "have documented cognition to improve following the use of renin angiotensin inhibitors and calcium channel blockers in the hypertensive elderly. That blood pressure lowering did not affect cognition in HOPE-3 is disappointing but not entirely unexpected since the majority of patients were normotensive at baseline. In normotensive patients reduction in blood pressure not only has no effect on cardiovascular events (as shown) but also may actually worsen cerebral perfusion and even cause a J-curve phenomenon. The good news in HOPE-3 is that rosuvastatin had no negative effect on cognition, while being highly effective in reducing cardiovascular outcomes."
Ralph Sacco, MD, of University of Miami, agreed at an American Heart Association press conference that an important finding was the absence of any signal for harm with statin treatment. He said that it was difficult to detect a difference in a population that was somewhat healthier than expected. He held out hope that significant benefits might be found by treating, on the one hand, higher risk populations or, on the other hand, younger patients for a longer period of time. Bosch agreed that earlier intervention may be the best way to achieve a beneficial effect.