SPRINT extended after results suggest intensive BP control reduces cognitive impairment

Full results from the SPRINT MIND trial, published Jan. 28 in JAMA, suggest intensive blood pressure control at a systolic target of less than 120 mm Hg could reduce the likelihood of mild cognitive impairment (MCI) that leads to dementia and Alzheimer’s.

Jeff D. Williamson, MD, et al.’s findings were initially reported at the Alzheimer’s Association International Conference in Chicago last July, at which point the researchers concluded their pool of more than 8,500 hypertensive subjects fared better cognitively after lowering their blood pressure (BP) to a max of 120 mm Hg. Compared to control patients whose BP threshold was 140 mm Hg, those in the intensive study group saw significantly lower rates of MCI.

But, Williamson and his team noted, MCI wasn’t a primary endpoint for the study. SPRINT’s primary cognitive outcome was the occurrence of adjudicated probable dementia, with a secondary outcome of MCI. And after an intervention period of three years and a mean follow-up of five, the researchers couldn’t prove intensive BP intervention lowered the incidence of dementia.

The trial randomized 8,563 patients with high blood pressure to a systolic BP target of less than 120 mm Hg—the intensive treatment—or 140 mm Hg. Over the study period, 149 patients in the intensive treatment group developed probable dementia compared to 176 in the standard treatment group (7.2 cases per 1,000 person-years versus 8.6 cases)—a difference that wasn’t statistically significant.

On the other hand, intensive BP control seemed to significantly reduce the risk of MCI, with a rate of 14.6 cases per 1,000 person-years in the intensive cohort and a rate of 18.3 cases per 1,000 person-years in the standard cohort. A combined secondary endpoint of MCI or probable dementia yielded a rate of 20.2 cases per 1,000 person-years in the intensive group and 24.1 cases per 1,000 person-years in the standard group.

“There is some indication that intensive BP control may be beneficial,” Williamson et al. wrote. “This is the first trial, to our knowledge, to demonstrate an intervention that significantly reduces the occurrence of MCI, a well-established risk factor for dementia, as well as the combined occurrence of MCI or dementia. However, some caution should be exercised in interpreting this result, both because MCI was not the primary cognitive outcome of the trial and because it is not clear what this effect may mean for the longer-term incidence of dementia.”

MCI considerably increases the risk of progression to dementia, the authors said, but that progression isn’t ever certain and could potentially be reversed. They said the trial was also terminated early due to the success of its first portion, a composite of cardiovascular events and all-cause mortality, which limited the scope of SPRINT’s cognitive outcomes.

To make up for the loss, the Alzheimer’s Association awarded more than $800,000 to the SPRINT MIND 2.0 study to extend the first trial and assess the long-term risk of dementia in the same hypertensive patients.

“SPRINT MIND 2.0 and the work leading up to it offers genuine, concrete hope,” Maria C. Carillo, PhD, chief science officer for the Alzheimer’s Association, said in a release. “MCI is a known risk factor for dementia, and everyone who experiences dementia passes through MCI. When you prevent new cases of MCI, you are preventing new cases of dementia.”

The seed money will allow SPRINT researchers to build on their results with a two-year extension, at the end of which they’ll hopefully have a more definitive answer about the relationship between BP control and dementia risk. SPRINT MIND 2.0 is slated to pick up in early 2019, which would make additional results available a year earlier than previously anticipated.

“We are filling the gaps in Alzheimer’s research, and—with the support of our donors and partners—we act rapidly to maximize opportunities,” Carillo said. “Proof that lowering blood pressure can lower risk for dementia may be key to improving the lives of millions of people around the world.”