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NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.
Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Bosch reported on the 1,626 subjects who were at least 70 years old at baseline – their mean age was 75 – and who completed a battery of cognitive and functional status tests and questionnaires at baseline.
The primary outcome in the HOPE-3 cognition substudy was decline over time in processing speed as measured on the Digit Symbol Substitution Test. There was an equal decline, regardless of whether patients were on blood pressure lowering, rosuvastatin, both, or double placebo.
Nor did statin- or blood pressure–lowering therapy have any impact on the secondary endpoints of decline in executive function as assessed by the modified Montreal Cognitive Assessment or the change in psychomotor speed as reflected in the Trail Making Test part B.
Moreover, treatment had no effect on age-related decline in overall functional status. During a mean of 5.6 years of follow-up, 22% of participants developed a new functional impairment regardless of whether they were on blood pressure– and/or cholesterol-lowering medication or double placebo.
Intriguingly, however, subgroup analyses provided a glimmer of hope. Patients who were in the top tertile for blood pressure at baseline, with a systolic blood pressure of 133 mm Hg or more, as well as the top tertile for LDL cholesterol, with an LDL of at least 112 mg/dL, showed significantly less decline in cognitive function over time if they were on rosuvastatin and blood pressure lowering than with double placebo. This higher-risk group showed a mean loss of only 4.65 points on the Digit Symbol Substitution Test, compared with an 11.8-point drop for those on double placebo. This is a post-hoc analysis, however, and the efficacy signal must be viewed as hypothesis generating, Dr. Bosch stressed.
Discussant Philip B. Gorelick, MD, MPH, said that he didn’t find the negative HOPE-3 cognition results surprising. After all, he coauthored a recent AHA/American Stroke Association Scientific Statement on the impact of hypertension on cognitive function that scrutinized 10 clinical hypertension trials and concluded that only two of them – SYST-EUR (Systolic Hypertension in Europe) and PROGRESS (Peridopril Protection Against Recurrent Stroke Study) – showed any indication that treating hypertension reduced cognitive decline (Hypertension. 2016. doi: 10.1161/HYP.0000000000000053).
Plus, a 2016 Cochrane Collaboration review of the published evidence concluded that, in older people at vascular risk, statins do not prevent cognitive decline or dementia after 3.5-5 years of treatment (Cochrane Database Syst Rev. 2016 Jan 4;[1]:CD003160).
“The horse may be out of the barn for many of our patients when we start intervening later in life. That’s not to say it can’t work, but the Alzheimer’s changes and disease process are beginning 20 or 30 years earlier, so we’ve got to intervene earlier,” said Dr. Gorelick, professor of translational science and molecular medicine at the Michigan State University College of Human Medicine, Grand Rapids.
Dr. Bosch concurred. “We know that, in epidemiologic studies, midlife hypertension is strongly associated with later cognitive impairment. We’ve missed the boat on the 70-year-olds,” she said. “We need to start treatment earlier and probably for longer.”
Dr. Bosch reported having no financial conflicts regarding the HOPE-3 study, which was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Dr. Gorelick reported serving as a consultant to Novartis regarding blood pressure lowering and maintenance of cognition.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Nearly 6 years of blood pressure lowering and statin therapy in elderly patients with moderate vascular risk did not prevent cognitive decline relative to placebo, but the treatment did not worsen it, either.
Data source: This analysis of cognitive and functional outcomes in the randomized multicenter HOPE-3 trial included 1,626 participants who were at least 70 years old at baseline, when they were randomized to blood pressure lowering or placebo and rosuvastatin or placebo and followed for a mean of 5.6 years.
Disclosures: The HOPE-3 study was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. The presenter reported having no financial conflicts of interest.
