title: Limitations of analyses based on achieved blood pressure: lessons from the African American study of kidney disease and hypertension trial.
abstract: Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this article was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1094) in the African-American Study of Kidney Disease and Hypertension Trial were randomly assigned to either usual BP goal defined by a mean arterial pressure goal of 102 to 107 mm Hg or lower BP goal defined by a mean arterial pressure goal of ≤92 mm Hg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate and a composite of a decrease in glomerular filtration rate by >50% or >25 mL/min per 1.73 m(2), requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in glomerular filtration rate or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10-mm Hg increment in mean follow-up achieved mean arterial pressure was associated with a 0.35 mL/min per 1.73 m(2) (95% CI: 0.08 to 0.62 mL/min per 1.73 m(2); P=0.01) faster mean glomerular filtration rate decline and a 17% (95% CI: 5% to 32%; P=0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, attributed in part to confounding of achieved BP with comorbidities, disease severity, and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.
authors.affiliation: Department of Medicine and Center for Research on Health Care, University of Pittsburgh, School of Medicine, 230 McKee Place, Suite 600, Pittsburgh, PA 15213, USA. davisem@upmc.edu
authors.forename: Esa M
authors.initials: EM
authors.lastname: Davis
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.forename: Xuelei
authors.initials: X
authors.lastname: Wang
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
authors.forename: Robert
authors.initials: R
authors.lastname: Toto
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lipkowitz
authors.forename: Velvie A
authors.initials: VA
authors.lastname: Pogue
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
mesh_terms: D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D016016:Proportional Hazards Models; D017257:Ramipril / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine; D008790:Metoprolol; D017257:Ramipril