Systolic Blood Pressure Response in SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes): A Possible Explanation for Discordant Trial Results

Abstract

BackgroundSPRINT (Systolic Blood Pressure Intervention Trial) and the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial used similar interventions but produced discordant results. We investigated whether differences in systolic blood pressure (SBP) response contributed to the discordant trial results.Methods and ResultsWe evaluated the distributions of SBP response during the first year for the intensive and standard treatment groups of SPRINT and ACCORD using growth mixture models. We assessed whether significant differences existed between trials in the distributions of SBP achieved at 1 year and the treatment‐independent relationships of achieved SBP with risks of primary outcomes defined in each trial, heart failure, stroke, and all‐cause death. We examined whether visit‐to‐visit variability was associated with heterogeneous treatment effects. Among the included 9027 SPRINT and 4575 ACCORD participants, the difference in mean SBP achieved between treatment groups was 15.7 mm Hg in SPRINT and 14.2 mm Hg in ACCORD, but SPRINT had significantly less between‐group overlap in the achieved SBP (standard deviations of intensive and standard groups, respectively: 6.7 and 5.9 mm Hg in SPRINT versus 8.8 and 8.2 mm Hg in ACCORD; P<0.001). The relationship between achieved SBP and outcomes was consistent across trials except for stroke and all‐cause death. Higher visit‐to‐visit variability was more common in SPRINT but without treatment‐effect heterogeneity.Conclusions SPRINT and ACCORD had different degrees of separation in achieved SBP between treatment groups, even as they had similar mean differences. The greater between‐group overlap of achieved SBP may have contributed to the discordant trial results.

Cardiovascular outcomes and achieved blood pressure in patients with and without diabetes at high cardiovascular risk

“…26 A significant difference between diabetes and no diabetes according to BP lowering on outcomes was not observed. 26 A somewhat smaller risk reduction of major cardiovascular events in diabetes compared with no diabetes was recently reported, 27 however, these differences were small. Nevertheless, the new guidelines of the AHA 4 and of the ESC 6 recommended SBP targets in cardiovascular high risk patients to 120-130 mmHg.…”

“…Recent post hoc analyses of SPRINT and ACCORD were showing that the lower BP goals were more strictly achieved in the SPRINT trial than in the ACCORD trial with a greater variation in the ACCORD trial. 26,27…”

Effects of Intensive Systolic Blood Pressure Lowering on Cardiovascular Events and Mortality in Patients With Type 2 Diabetes Mellitus on Standard Glycemic Control and in Those Without Diabetes Mellitus: Reconciling Results From ACCORD BP and SPRINT

“…These results, however, were primarily driven by the SPRINT data 19. Differences in blood pressure measurement techniques,20 differences in the achieved SBP separations,21 and differences in selection criteria22 have also been proposed as potential explanations. Although these explanations are possibilities, other potential explanations merit consideration.…”

Response to Comment on Buckley et al. Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP. Diabetes Care 2017;40:1733–1738

“…Although we continue to support our conclusions that SPRINT-eligible ACCORD-BP participants benefited from intensive blood pressure lowering, we recognize that our results do not exclude the important contributions from other factors as explanations for the discrepant results of ACCORD-BP and SPRINT (2). Indeed, several alternative hypotheses have been proposed in an attempt to explain the discordant results of SPRINT and ACCORD-BP (3,4). We therefore welcome the contributions by Mi and Mukamal to this important conversation.…”