Intensive glucose control and macrovascular outcomes in type 2 diabetes. Export

@article{citeulike:5399434, abstract = {AIMS/HYPOTHESIS: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. METHODS: A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. RESULTS: A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9\% (HR 0.91, 95\% CI 0.84-0.99), primarily because of a 15\% reduced risk of myocardial infarction (HR 0.85, 95\% CI 0.76-0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95\% CI 0.90-1.20) and 1.10 for cardiovascular death (95\% CI 0.84-1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95\% CI 1.91-3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95\% CI 0.89-1.13, vs HR 0.84, 95\% CI 0.74-0.94, respectively; interaction p = 0.04). CONCLUSIONS/INTERPRETATION: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.}, author = {Turnbull, F. M. and Abraira, C. and Anderson, R. J. and Byington, R. P. and Chalmers, J. P. and Duckworth, W. C. and Evans, G. W. and Gerstein, H. C. and Holman, R. R. and Moritz, T. E. and Neal, B. C. and Ninomiya, T. and Patel, A. A. and Paul, S. K. and Travert, F. and Woodward, M.}, citeulike-article-id = {5399434}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00125-009-1470-0}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19655124}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19655124}, citeulike-linkout-3 = {http://www.springerlink.com/content/p72416968l2725t4}, comment = {MedWire News: A meta-analysis of four major trials testing intensive glucose lowering underscores that modest reductions in major macrovascular events achieved with this approach are countered by an increase in major hypoglycemia, report investigators in the journal Diabetologia. To provide more precise estimates of the effects of glucose-lowering on major cardiovascular events, a prospectively planned meta-analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), United Kingdon Prospective Diabetes Study (UKPDS), and Veterans Affairs Diabetes Trial (VADT) has been conducted. The trials randomized a total of 27,049 participants with Type 2 diabetes, most of whom also had at least one other risk factor for cardiovascular disease. ACCORD, ADVANCE, and VADT allocated participants equally to intensive versus less intensive glycemic control groups, while the UKPDS allocated 70\% of its participants to an intensive group and 30\% to a less intensive group. The primary outcome was a composite of major cardiovascular events, defined as death from cardiovascular causes (including sudden death), nonfatal myocardial infarction, and non-fatal stroke. The mean duration of study follow-up was 4.4 years. Overall, intensive glycemic control reduced final visit glycated hemoglobin (HbA1c) by a mean of 0.88\% more than less intensive glycemic control, with an associated 9\% reduction in the risk for major cardiovascular events, primarily because of a 15\% reduced risk for myocardial infarction. No significant effect was seen on cardiovascular death, although there was a 10\% trend for a relative risk increase. Severe hypoglycemic events were more common in the intensive group, at 1071 events, than in the less intensive group, at 372 events, reflecting a 2.5-fold increase in the risk for severe hypoglycemia. Subgroup analyses suggest that participants without a history of macrovascular disease at randomization appeared to benefit from more intensive glycemic control, whereas those with a history of a macrovascular disease did not. ” Exploration of the pooled data made possible by this collaboration of the four studies has generated the best estimate that is available currently of the cardiovascular benefits of more intensive glycemic control,” write Fiona Turnbull (University of Sydney, Australia) and colleagues. ” The analyses suggest that glucose lowering regimens should be tailored to the individual,” the investigators conclude. MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. {\copyright} Current Medicine Group Ltd; 2009}, day = {1}, doi = {10.1007/s00125-009-1470-0}, issn = {1432-0428}, journal = {Diabetologia}, keywords = {cardiovascular, chd, diabetes, meta-analysis}, month = {November}, number = {11}, pages = {2288--2298}, posted-at = {2009-08-27 00:54:27}, priority = {2}, title = {Intensive glucose control and macrovascular outcomes in type 2 diabetes.}, url = {http://dx.doi.org/10.1007/s00125-009-1470-0}, volume = {52}, year = {2009} }

TY - JOUR ID - citeulike:5399434 L3 - citeulike-article-id:5399434 N2 - AIMS/HYPOTHESIS: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. METHODS: A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. RESULTS: A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84-0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76-0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90-1.20) and 1.10 for cardiovascular death (95% CI 0.84-1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91-3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p = 0.04). CONCLUSIONS/INTERPRETATION: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual. IS - 11 JF - Diabetologia SN - 1432-0428 EP - 2298 TI - Intensive glucose control and macrovascular outcomes in type 2 diabetes. VL - 52 SP - 2288 KW - cardiovascular KW - chd KW - diabetes KW - meta-analysis N1 - MedWire News: A meta-analysis of four major trials testing intensive glucose lowering underscores that modest reductions in major macrovascular events achieved with this approach are countered by an increase in major hypoglycemia, report investigators in the journal Diabetologia. To provide more precise estimates of the effects of glucose-lowering on major cardiovascular events, a prospectively planned meta-analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), United Kingdon Prospective Diabetes Study (UKPDS), and Veterans Affairs Diabetes Trial (VADT) has been conducted. The trials randomized a total of 27,049 participants with Type 2 diabetes, most of whom also had at least one other risk factor for cardiovascular disease. ACCORD, ADVANCE, and VADT allocated participants equally to intensive versus less intensive glycemic control groups, while the UKPDS allocated 70% of its participants to an intensive group and 30% to a less intensive group. The primary outcome was a composite of major cardiovascular events, defined as death from cardiovascular causes (including sudden death), nonfatal myocardial infarction, and non-fatal stroke. The mean duration of study follow-up was 4.4 years. Overall, intensive glycemic control reduced final visit glycated hemoglobin (HbA1c) by a mean of 0.88% more than less intensive glycemic control, with an associated 9% reduction in the risk for major cardiovascular events, primarily because of a 15% reduced risk for myocardial infarction. No significant effect was seen on cardiovascular death, although there was a 10% trend for a relative risk increase. Severe hypoglycemic events were more common in the intensive group, at 1071 events, than in the less intensive group, at 372 events, reflecting a 2.5-fold increase in the risk for severe hypoglycemia. Subgroup analyses suggest that participants without a history of macrovascular disease at randomization appeared to benefit from more intensive glycemic control, whereas those with a history of a macrovascular disease did not. “Exploration of the pooled data made possible by this collaboration of the four studies has generated the best estimate that is available currently of the cardiovascular benefits of more intensive glycemic control,” write Fiona Turnbull (University of Sydney, Australia) and colleagues. “The analyses suggest that glucose lowering regimens should be tailored to the individual,” the investigators conclude. MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009 AU - Turnbull, FM AU - Abraira, C AU - Anderson, RJ AU - Byington, RP AU - Chalmers, JP AU - Duckworth, WC AU - Evans, GW AU - Gerstein, HC AU - Holman, RR AU - Moritz, TE AU - Neal, BC AU - Ninomiya, T AU - Patel, AA AU - Paul, SK AU - Travert, F AU - Woodward, M PY - 2009/11/01/ UR - http://dx.doi.org/10.1007/s00125-009-1470-0 ER -