Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients

Abstract

A reduction of either blood pressure or glycemia decreases some microvascular complications of type 2 diabetes, and we studied here their combined effects. In total, 4733 older adults with established type 2 diabetes and hypertension were randomly assigned to intensive (systolic blood pressure less than 120 mm Hg) or standard (systolic blood pressure less than 140 mm Hg) blood pressure control, and separately to intensive (HbA1c less than 0.060) or standard (HbA1c 0.070-0.079) glycemic control. Prespecified microvascular outcomes were a composite of renal failure and retinopathy and nine single outcomes. Proportional hazard regression models were used without correction for type I error due to multiple tests. During a mean follow-up of 4.7 years, the primary outcome occurred in 11.4% of intensive and 10.9% of standard blood pressure patients (hazard ratio 1.08), and in 11.1% of intensive and 11.2% of standard glycemia control patients. Intensive blood pressure control only reduced the incidence of microalbuminuria (hazard ratio 0.84), and intensive glycemic control reduced the incidence of macroalbuminuria and a few other microvascular outcomes. There was no interaction between blood pressure and glycemic control, and neither treatment prevented renal failure. Thus, in older patients with established type 2 diabetes and hypertension, intensive blood pressure control improved only 1 of 10 prespecified microvascular outcomes. None of the outcomes were significantly reduced by simultaneous intensive treatment of glycemia and blood pressure, signifying the lack of an additional beneficial effect from combined treatment.

Figure 1

Effect of intensive versus standard blood pressure (BP) and glycemic control on microvascular outcomes. Forest plot depicting effects of randomized blood pressure (a) and glycemia (b) treatments on selected microvascular events with P-values for tests of two-way interactions between treatments (“Interact P-value” column).

Figure 2

Follow-up urine albuminuria and renal failure (RF, dialysis or serum creatinine 4292 lmol/l) in 4232 ACCORD-BP Trial participants with at least one follow-up urine albumin measurement before occurrence of RF. Follow-up microalbuminuria (urine albumin-to-creatinine ratio or UACRX3.39 mg albumin/mmol creatinine) and macroalbuminuria (UACRX33.9 mg albumin/mmol creatinine) was determined by urinalysis performed every 2 years. Participants with microalbuminuria or macroalbuminuria at baseline, but a maximum urine albumin-to-creatinine ratio value o3.39 mg/mmol at all subsequent assessments regress to ‘No microalbuminuria or macroalbuminuria’. Participants with macroalbuminuria at baseline but a maximum urine albumin-to-creatinine ratio value X3.39 mg/mmol and <33.9 mg/mmol at all subsequent assessments regress to ‘Microalbuminuria’. Of 124 participants who experienced RF during the course of the trial, 2 did not have baseline urinalysis performed, 6 did not have post-randomization urinalysis performed, and 42 had onset of RF before the first post-randomization urinalysis and are not included in the figure.