Long-term mortality benefit of BP lowering in type 2 diabetes [ADVANCE-ON trial]
1. The mortality benefit of blood pressure (BP) lowering therapy observed in the ADVANCE trial persisted at 6-year post-trial follow-up.
2. Intensive glucose control showed no benefit in reducing overall mortality or major macrovascular events compared to standard glucose control.
Evidence Rating Level: 2 (Good)
Study Rundown: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial was a multicentre, randomized controlled study that included over 10,000 patients with type 2 diabetes. The 2-by-2 factorial trial assessed the benefit of BP-lowering therapy compared to placebo, and intensive glucose control compared to standard glucose control to important clinical outcomes in this group. One of the main findings was that BP-lowering with combined perindopril and indapamide was associated with a reduction in overall mortality and death from cardiovascular causes. Results of the trial also showed that intensive glucose control, defined as a glycated hemoglobin level less than 6.5%, did not in-crease mortality and reduced the incidence of combined major macrovascular and microvascular events, primarily due to a reduction in the incidence of nephropathy.
The ADVANCE observational study (ADVANCE-ON) is a post-trial follow-up of surviving partici-pants from the ADVANCE trial for a median of 5.9 years. Main findings from the post-trial follow-up include that the mortality benefit of BP-lowering therapy remained significant though attenuat-ed at six years post-trial and there was no long-term benefit of intensive glucose control on overall mortality or major macrovascular events when compared to standard glucose control. This study contributes to our understanding of long-term clinical outcomes of therapy in patients with type 2 diabetes. Limitations include incomplete follow-up of the original trial participants and less stringent post-trial follow-up procedures (often by telephone or questionnaires).
Click to read the study in NEJM
In-Depth [observational study]: This post-trial follow-up observational study included 8,494 pa-tients of 11,140 participants from the original trial. The primary outcomes measured were all-cause mortality and major macrovascular events (composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause). The median in-trial and post-trial follow-up periods were 4.4 years and 5.9 years, respectively, for the BP-lowering comparison and 5.0 years and 5.4 years, respectively, for the glucose control comparison.
During the randomized ADVANCE trial, there was a significant between-group difference in blood pressure between the group receiving combined perindopril-indapamide and the placebo group. This difference was no longer evident 6 months after the trial and blood pressure levels were similar between the two groups during the post-trial period. The reduction in all-cause mortality observed in the perindopril-indapamide group during the trial remained significant but attenuated in the post-trial follow-up (hazard ratio, 0.91; 95% CI, 0.84 to 0.99; P=0.03). The significant be-tween-group difference in glycated haemoglobin levels observed in the randomized trial was no longer evident at the first post-trial visit and levels remained similar throughout the post-trial peri-od. There was no benefit observed with intensive glucose control on all-cause mortality or major macrovascular events compared to standard glucose control.
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