TitleEffect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial.
Publication TypeJournal Article
Year of Publication2016
AuthorsPeralta, CA, McClure, LA, Scherzer, R, Odden, MC, White, CL, Shlipak, M, Benavente, O, Pergola, P
Date Published2016 Feb 09
KeywordsAged, Blood Pressure, Blood Pressure Determination, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney, Male, Middle Aged, Platelet Aggregation Inhibitors, Secondary Prevention, Stroke, Lacunar, Treatment Outcome

BACKGROUND: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established.

METHODS AND RESULTS: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06).

CONCLUSIONS: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.

Alternate JournalCirculation
PubMed ID26762524
PubMed Central IDPMC4829068
Grant ListP30 AG044281 / AG / NIA NIH HHS / United States
R01 AG046206 / AG / NIA NIH HHS / United States
1R01AG046206-01A1 / AG / NIA NIH HHS / United States
5R03DK095877-03 / DK / NIDDK NIH HHS / United States