Intensive BP Meds in Elderly May Safely Slow Hypertensive Brain Damage

March 20, 2019

NEW ORLEANS — Intensive drug therapy to lower blood pressure (BP), compared with treatment to a more liberal BP target, seemed to slow the progression of subcortical brain lesions on MRI in a 3-year randomized study of patients 75 years and older.

But no improvements in cognitive testing or mobility went along with the gains seen on MRI in the more aggressively managed patients, in whom antihypertensive therapy was aimed at a systolic BP below 130 mm Hg, compared with a target below 145 mm Hg, guided by 24-hour ambulatory BP monitoring.

Interestingly, patients managed to the lower target showed a 76% reduction in major cardiovascular (CV) events (P < .01) compared with the less-intensively managed group.

"Even in a small study like this, there were much fewer cardiovascular events in the intensive-treated group, and these were events like myocardial infarction, stroke, hospitalization for heart failure, transient ischemic attack — all things that you would expect in a hypertensive older population," said William B. White, MD, University of Connecticut School of Medicine, Farmington, at press conference on the findings.

White, a principal investigator on the trial, called INFINITY, presented its results here at the ACC 2019 Scientific Session (ACC.19).

They are consistent with results from the SPRINT trial and other research, which have shown that aggressive BP targets are safe and clinically advantageous compared with more conservative BP goals in older patients with hypertension, White told theheart.org | Medscape Cardiology. But the current trial is rare for showing corresponding MRI confirmation of a benefit against chronic brain damage.

In SPRINT, people 50 years and older with hypertension and other CV risk factors were treated to systolic BP targets of either 120 or 140 mm Hg or below. As previously reported, those in the intensive-therapy group showed significantly reduced rates of the primary composite clinical end point and all-cause and CV mortality.

Follow-up analyses from the trial suggested that the clinical benefits of the lower BP target extended safely to its patients 75 years and older, although without improving mobility.

And the ancillary SPRINT-MIND study suggested that intensive BP management in a defined SPRINT cohort improved measures of mild cognitive impairment over an average of 5 years. That was a secondary end point, however; the primary end point of dementia was not significantly different between treatment groups.

In the current study, whereas there wasn't a benefit for mobility or on cognitive testing in the group managed to the more aggressive target, White said such improvement would likely have emerged had the study been able to last "a few more years."

That's based on their slower progression of subcortical small-vessel disease of the brain, as shown by periventricular white-matter hyperintensities (WMH) on MRI, he said. Such findings are known to reflect end-organ disease from chronic hypertension.

On the basis of the MRI results, the current study might well have shown improvement in cognitive function with intensive BP management "had they followed these people out for 5 years," agreed Eileen Handberg, PhD, ARNP, BC, University of Florida, Gainesville, in an interview.

"I think these data are extremely meaningful" and that it's worth looking beyond the lack of effect on the primary functional outcomes and more to the MRI findings, said Handberg, who wasn't associated with INFINITY.

"This is another dataset that shows that lowering blood pressure in the elderly is extremely important. You can accomplish it without fear of them falling," she said.

Clinical practice often seems apprehensive about hypotension in the elderly, and "I think we exclude people from aggressive blood pressure lowering because of this unrealized fear. The fact that they were able to demonstrate a mechanistic change in brain-matter intensity is important."

So, she said, "to me this trial is very generalizable and adds to the data that generated the guideline that says we should be treating patients older than 65 to 130 over 80," Handberg said.

And "it should add another strong piece of information to say that treating patients who are 80 years old to 130/80 mm Hg is safe and effective and reduces cardiovascular risk, reduces stroke."

The open-label study conducted at a single center randomly assigned 199 patients 75 years and older (mean, 81 years) with normal cognition and mobility but evidence of WMH on baseline MRI and hypertension to either intensive or conventional BP medical management.

The goals were 130 mm Hg and 145 mm Hg, respectively, per contemporary standards when the study was designed and as tracked by 24-hour BP monitoring.

Mean systolic BP was 150 mm Hg at baseline. Three years later, mean BP was 131/65 mm Hg in the intensive-management group and 146/74 mm Hg in the standard-management group.

Patients in the intensive-management group showed about 40% less progression of WMH on MRI over the trial's 3 years.

MRI Findings Over 3 Years in the Intensive- and Standard-Management Groups
End Point Intensive Management (n = 99) Standard Management (n = 100) P Value
Mean intracranial cavity volume, mL 1452 1503 .02
Mean increase from Baseline in WMH, % 0.29 0.48 .03

In addition, a sensitivity analysis that involved only patients who maintained their assigned BP target across the entire study showed an even more pronounced difference in change in WMH between the two groups.

In that analysis, the WMH percentage increased by a mean of 0.23 in 49 patients on intensive therapy and by a mean of 0.58 in the 54 standard-therapy patients (P < .01).

There were no differences between the groups in gait speed or any other mobility test. Only one of several tests of cognitive function — sequential reaction time — was significantly improved in the intensive-therapy group, compared with the other group (P < .01), "although it is an important test of processing speed and executive function of the brain," White observed.

Clinical Outcomes Over 3 Years in the Intensive- and Standard-Management Groups
End Points Intensive Management, % (n = 99) Standard Management, % (n = 100)
Death 2 4
Nonfatal CV event 4 17*
Falls with injury 4 5
Falls without injury 31 32
Syncope or near syncope 4 4
*Risk ratio, 0.24; 95% CI, 0.08-  0.68); P < .01 for intensive vs standard management

White had no relevant disclosures. Handberg discloses receiving consulting fees or honoraria from Bristol-Myers Squibb and conducting research or receiving research grants from Aastrom Biosciences, Amorcyte, Biocardia, Capricor, Cytori Therapeutics, Direct Flow Medical, Medtronic, Merck, Mesoblast, Sanofi Aventis, and Everyfit; and receiving "other financial benefit" from Relypsa, AstraZeneca, Boerhinger Ingleheim, Daiichi Sankyo, and Gilead Sciences.

American College of Cardiology (ACC) 2019 Scientific Session: Abstract 409-12. Presented March 18, 2018.

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