A secondary analysis of data from the SPRINT trial revealed that use of stimulating versus inhibiting antihypertensives was associated with 26% lower risk of amnestic mild cognitive impairment (MCI) and a non-significantly lower risk of probable dementia, researchers report in JAMA Network Open.
"Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline," Dr. Zachary A. Marcum, of the School of Pharmacy at the University of Washington, in Seattle, and colleagues write.
"The main message for clinicians at this point is to emphasize the importance of achieving blood pressure targets as a dementia-risk-reduction strategy," Dr. Marcum added in an email to Reuters Health.
Antihypertensives that stimulate type-2 and -4 angiotensin II receptors include angiotensin-II-receptor type-1 blockers, dihydropyridine calcium-channel blockers and thiazide diuretics. Those that inhibit these receptors include ACE inhibitors, beta-blockers and nondihydropyridine calcium-channel blockers.
SPRINT enrolled participants ages 50 and older with untreated systolic blood pressure of 130 to 180 mmHg, as well as additional cardiovascular risk factors, including clinical or subclinical cardiovascular disease, chronic kidney disease, or age of 75 or older.
The new analysis includes 8,685 patients who were taking antihypertensive medications at the six-month study visit. Their mean age was 67, 64% were male, and 57% were non-Hispanic white; 30% used exclusively stimulating antihypertensive medications, and 18% used exclusively inhibiting regimens. Users of stimulating regimens were likelier to be women, Black and randomized to intensive treatment.
Over 4.8 years of follow-up, there were 45 cases of amnestic MCI or probable dementia per 1,000 person-years among users of exclusively stimulating antihypertensive regimens, versus 59 cases among users of exclusively inhibiting regimens (hazard ratio, 0.76; 95% CI, 0.66 to 0.87).
Amnestic MCI alone occurred at rates of 40 versus 54 cases per 1,000 person-years (HR, 0.74; 95% CI, 0.64 to 0.87), and probable dementia alone occurred at rates of eight versus 10 cases per 1,000 person-years (HR, 0.80; 95% CI, 0.57 to 1.14) in the same two groups, respectively.
Dr. Ihab Hajjar, a geriatrician and dementia specialist at Emory University, in Atlanta, who was not involved in the study, praised its large sample size, its "detailed antihypertensive regimen and the use of cognitive diagnostic outcome that has been adjudicated."
He cautioned, however, that "the choice of the medication by the study providers was not random and bias-by-indication remains an issue." Still, these and other recent data support the idea that angiotensin-II-receptor blockers "are likely to have a clear advantage over other antihypertensive classes when it comes to cognitive function," Dr. Hajjar told Reuters Health by email.
Dr. Daniel Nation of the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, who also was not involved in the study, told Reuters Health by email that "by examining amnestic MCI as an outcome, the findings indicate relevance for earlier-stage cognitive changes, as opposed to dementia, which is later-stage impairment."
He said the study "adds to mounting literature implicating the renin-angiotensin system in cognitive decline, and hopefully these studies will spur additional clinical trials."
The study did not have commercial funding. Some authors disclosed ties to drugmakers.
SOURCE: https://bit.ly/3ru5Mhb JAMA Network Open, online January 28, 2022.
By Scott Baltic
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