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

Sophia Zoungas, John Chalmers, Bruce Neal, Laurent Billot, Qiang Li, M. Biostat, 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 & 9 others David R. Matthews, Carl E. Mogensen, Vlado Perkovic, Neil Poulter, Anthony Rodgers, Bryan Williams, Stephen MacMahon, Anushka Patel, Mark Woodward

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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.

Original languageEnglish
Pages (from-to)1392-1406
Number of pages15
JournalNew England Journal of Medicine
Volume371
Issue number15
DOIs
Publication statusPublished - 9 Oct 2014

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Type 2 Diabetes Mellitus
Blood Glucose
Blood Pressure
Glucose
Indapamide
Confidence Intervals
Perindopril
Cause of Death
perindopril drug combination indapamide
Glycosylated Hemoglobin A
Mortality
Gliclazide
Control Groups
Risk Reduction Behavior
Random Allocation
Vascular Diseases
Placebos
Therapeutics

Cite this

Zoungas, S., Chalmers, J., Neal, B., Billot, L., Li, Q., Biostat, M., ... Woodward, M. (2014). Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. New England Journal of Medicine, 371(15), 1392-1406. https://doi.org/10.1056/NEJMoa1407963
Zoungas, Sophia ; Chalmers, John ; Neal, Bruce ; Billot, Laurent ; Li, Qiang ; Biostat, M. ; Hirakawa, Yoichiro ; Arima, Hisatomi ; Monaghan, Helen ; Joshi, Rohina ; Colagiuri, Stephen ; Cooper, Mark E. ; Glasziou, Paul ; Grobbee, Diederick ; Hamet, Pavel ; Harrap, Stephen ; Heller, Simon ; Lisheng, Liu ; Mancia, Giuseppe ; Marre, Michel ; Matthews, David R. ; Mogensen, Carl E. ; Perkovic, Vlado ; Poulter, Neil ; Rodgers, Anthony ; Williams, Bryan ; MacMahon, Stephen ; Patel, Anushka ; Woodward, Mark. / Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 15. pp. 1392-1406.
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title = "Follow-up of blood-pressure lowering and glucose control in type 2 diabetes",
abstract = "BACKGROUNDIn 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.METHODSWe 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.RESULTSThe 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.CONCLUSIONSThe 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.",
author = "Sophia Zoungas and John Chalmers and Bruce Neal and Laurent Billot and Qiang Li and M. Biostat and Yoichiro Hirakawa and Hisatomi Arima and Helen Monaghan and Rohina Joshi and Stephen Colagiuri and Cooper, {Mark E.} and Paul Glasziou and Diederick Grobbee and Pavel Hamet and Stephen Harrap and Simon Heller and Liu Lisheng and Giuseppe Mancia and Michel Marre and Matthews, {David R.} and Mogensen, {Carl E.} and Vlado Perkovic and Neil Poulter and Anthony Rodgers and Bryan Williams and Stephen MacMahon and Anushka Patel and Mark Woodward",
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Zoungas, S, Chalmers, J, Neal, B, Billot, L, Li, Q, Biostat, M, Hirakawa, Y, Arima, H, Monaghan, H, Joshi, R, Colagiuri, S, Cooper, ME, Glasziou, P, Grobbee, D, Hamet, P, Harrap, S, Heller, S, Lisheng, L, Mancia, G, Marre, M, Matthews, DR, Mogensen, CE, Perkovic, V, Poulter, N, Rodgers, A, Williams, B, MacMahon, S, Patel, A & Woodward, M 2014, 'Follow-up of blood-pressure lowering and glucose control in type 2 diabetes' New England Journal of Medicine, vol. 371, no. 15, pp. 1392-1406. https://doi.org/10.1056/NEJMoa1407963

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. / Zoungas, Sophia; Chalmers, John; Neal, Bruce; Billot, Laurent; Li, Qiang; Biostat, M.; Hirakawa, Yoichiro; Arima, Hisatomi; Monaghan, Helen; Joshi, Rohina; Colagiuri, Stephen; Cooper, Mark E.; Glasziou, Paul; Grobbee, Diederick; Hamet, Pavel; Harrap, Stephen; Heller, Simon; Lisheng, Liu; Mancia, Giuseppe; Marre, Michel; Matthews, David R.; Mogensen, Carl E.; Perkovic, Vlado; Poulter, Neil; Rodgers, Anthony; Williams, Bryan; MacMahon, Stephen; Patel, Anushka; Woodward, Mark.

In: New England Journal of Medicine, Vol. 371, No. 15, 09.10.2014, p. 1392-1406.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Follow-up of blood-pressure lowering and glucose control in type 2 diabetes

AU - Zoungas, Sophia

AU - Chalmers, John

AU - Neal, Bruce

AU - Billot, Laurent

AU - Li, Qiang

AU - Biostat, M.

AU - Hirakawa, Yoichiro

AU - Arima, Hisatomi

AU - Monaghan, Helen

AU - Joshi, Rohina

AU - Colagiuri, Stephen

AU - Cooper, Mark E.

AU - Glasziou, Paul

AU - Grobbee, Diederick

AU - Hamet, Pavel

AU - Harrap, Stephen

AU - Heller, Simon

AU - Lisheng, Liu

AU - Mancia, Giuseppe

AU - Marre, Michel

AU - Matthews, David R.

AU - Mogensen, Carl E.

AU - Perkovic, Vlado

AU - Poulter, Neil

AU - Rodgers, Anthony

AU - Williams, Bryan

AU - MacMahon, Stephen

AU - Patel, Anushka

AU - Woodward, Mark

PY - 2014/10/9

Y1 - 2014/10/9

N2 - BACKGROUNDIn 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.METHODSWe 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.RESULTSThe 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.CONCLUSIONSThe 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.

AB - BACKGROUNDIn 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.METHODSWe 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.RESULTSThe 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.CONCLUSIONSThe 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.

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DO - 10.1056/NEJMoa1407963

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VL - 371

SP - 1392

EP - 1406

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 15

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Zoungas S, Chalmers J, Neal B, Billot L, Li Q, Biostat M et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. New England Journal of Medicine. 2014 Oct 9;371(15):1392-1406. https://doi.org/10.1056/NEJMoa1407963