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  • Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

The New England journal of medicine (2014-09-23)
Sophia Zoungas, John Chalmers, Bruce Neal, Laurent Billot, Qiang Li, Yoichiro Hirakawa, Hisatomi Arima, Helen Monaghan, Rohina Joshi, Stephen Colagiuri, Mark E Cooper, Paul Glasziou, Diederick Grobbee, Pavel Hamet, Stephen Harrap, Simon Heller, Liu Lisheng, Giuseppe Mancia, Michel Marre, David R Matthews, Carl E Mogensen, Vlado Perkovic, Neil Poulter, Anthony Rodgers, Bryan Williams, Stephen MacMahon, Anushka Patel, Mark Woodward
ABSTRACT

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. 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. 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. 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.).

MATERIALS
Product Number
Brand
Product Description

Supelco
Gliclazide, Pharmaceutical Secondary Standard; Certified Reference Material
Perindopril for peak identification, European Pharmacopoeia (EP) Reference Standard
USP
Indapamide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Perindopril erbumine
Sigma-Aldrich
Gliclazide, powder, ≥98%
Supelco
Indapamide, analytical standard, for drug analysis
Gliclazide, European Pharmacopoeia (EP) Reference Standard
Perindopril tert-butylamine, European Pharmacopoeia (EP) Reference Standard
Perindopril for stereochemical purity, European Pharmacopoeia (EP) Reference Standard
Indapamide, European Pharmacopoeia (EP) Reference Standard