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

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.).

• Authors: 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, ADVANCE-ON Collaborative Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 371 Issue 15 Pg. 1392-406 (Oct 09 2014) ISSN: 1533-4406 [Electronic] United States
• PMID: 25234206 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Blood Glucose
• Drug Combinations
• Glycated Hemoglobin A
• Hypoglycemic Agents
• indapamide, perindopril drug combination
• Indapamide
• Gliclazide
• Perindopril

Topics

• Antihypertensive Agents (therapeutic use)
• Blood Glucose
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy, mortality)
• Drug Combinations
• Female
• Follow-Up Studies
• Gliclazide (administration & dosage)
• Glycated Hemoglobin (analysis)
• Humans
• Hypertension (complications, drug therapy)
• Hypoglycemic Agents (administration & dosage)
• Indapamide (therapeutic use)
• Male
• Middle Aged
• Perindopril (therapeutic use)
• Risk Factors