Lowering blood pressure reduces renal events in type 2 diabetes

Abstract

BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.

Trial registration: ClinicalTrials.gov NCT00145925.

Figure 1.

(A through C) Mean eGFR during follow-up according to treatment assignment in patients with normoalbuminuria (A), microalbuminuria (B), and macroalbuminuria (C) at baseline. R, randomization; Per-Ind, perindopril-indapamide treatment group.

Figure 2.

Effect of randomized treatment on all renal events (top) and the composite of all renal events, macrovascular events, or all-cause mortality (bottom) according to baseline SBP and DBP. The center of the diamond represents the estimate and its width the 95% CI for overall treatment effect. Solid boxes represent estimates of treatment effect in subgroups; the centers of the boxes are placed at the estimates of effect, the areas of boxes are proportional to the number of events, and horizontal lines represent the corresponding 95% CIs. The vertical dotted line represents the point estimate for overall effect. The “P trend” tested the consistency of treatment effect in subgroups.

Figure 3.

Effect of randomized treatment on all renal events in subgroups of participants defined by characteristics at baseline. For other conventions, see Figure 1. P > 0.1 for trend for all subgroup comparisons.

Figure 4.

Incidence of all renal events according to achieved BP levels, adjusted for age, gender, duration of diabetes, glycosylated hemoglobin, currently treated hypertension, history of macrovascular disease, electrocardiogram abnormalities (ventricular hypertrophy, Q waves, or atrial fibrillation), triglycerides, LDL cholesterol, HDL cholesterol, body mass index, current smoking, current alcohol use, and study drug. Solid boxes represent estimates of event rates, centers of which are placed at the intersection of the point estimate and median SBP value. Areas of the boxes are proportional to the number of events, and vertical bars represent 95% CI. The rate of all renal events was significantly associated with achieved SBP levels (P < 0.0001 for trend).