INtensive versus standard ambulatory blood pressure lowering to prevent functional DeclINe in the ElderlY (INFINITY)

Abstract

Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white matter hyperintensities (WMHs) on magnetic resonance imaging can occur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating 2 levels of ambulatory blood pressure (ABP) control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded end points, in patients ages ≥75 years with elevated 24-hour systolic blood pressure (BP) (145 mm Hg in the untreated state) who do not have unstable cardiovascular disease, heart failure, or stroke. The primary and key secondary outcomes in the trial are change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes in diffusion tensor imaging. Approximately 300 patients will be enrolled, and 200 randomized to 1 of 2 levels of ABP control (intensive to achieve a goal 24-hour systolic BP of ≤130 mm Hg or standard to achieve a goal 24-hour systolic BP of ≤145 mm Hg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ABP monitoring rather than clinic BP to reduce cerebrovascular disease.

Trial registration: ClinicalTrials.gov NCT01650402.

Figure 1. Design of the INFINITY Trial

–Intensive BP Treatment – goal 24-hour ambulatory systolic BP ≤ 130 mmHg ; Standard BP Treatment – goal 24-hour systolic BP ≤ 145 mmHg

Figure 2. Hypothesis Flow Path

Graphic representation of how our hypotheses relate to one another. Hypothesis 1 tests the combined effects of paths A, B, C, D & E i.e., the total effect of BP on mobility. Hypothesis 2 tests path A, Hypothesis 3 tests path D, The secondary hypotheses test path B+E; together these test the effect of BP on mobility mediated through BP’s effects on WMH and WM microstructure. An additional secondary hypothesis tests the relative importance of paths A and B to that of path C, i.e., the degree to which the effect of BP on mobility is explained by WMH. The final secondary hypothesis tests the relative importance of paths D and E to that of path C, i.e., the degree to which the effect of BP on mobility is explained by changes in WM microstructure.