Follow-up of blood-pressure lowering and glucose control in type 2 diabetes
Poulter, N; Hamet, P; Grobbee, D; Hirakawa, Y; Williams, B; Monaghan, H; Mogensen, CE; Harrap, S; Joshi, R; Heller, S; Marre, M; Lisheng, L; Cooper, ME; Chalmers, J; Glasziou, P; Billot, L; Mathews, DR; Woodward, M; Rodgers, A; Colagiuri, S; MacMahon, S; Arima, H; Li, Q; Perkovic, V; Patel, A; Mancia, G; Neal, B; Zoungas, S
Abstract
BACKGROUND:
In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up.
METHODS:
We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events.
RESULTS:
The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively.
CONCLUSIONS:
The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).
| Journal | N ENGL J MED |
| ISSN | 0028-4793 |
| Published | 09 Oct 2014 |
| Volume | 371 |
| Issue | 15 |
| Pages | 1392-406 |
| DOI | 10.1056/NEJMoa1407963 |
| Type | Journal Article |
| Sponsorship |