Glycemic Control, Preexisting Cardiovascular Disease, and Risk of Major Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: Systematic Review With Meta-Analysis of Cardiovascular Outcome Trials and Intensive Glucose Control Trials - PubMed (original) (raw)

Meta-Analysis

Glycemic Control, Preexisting Cardiovascular Disease, and Risk of Major Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: Systematic Review With Meta-Analysis of Cardiovascular Outcome Trials and Intensive Glucose Control Trials

Dario Giugliano et al. J Am Heart Assoc. 2019.

Abstract

Background The value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline. Methods and Results We did a meta-analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease ( P for interaction=0.021). The meta-regression analysis of all 12 trials demonstrated a significant ( P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium-glucose cotransporter-2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease. Conclusions Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE.

Keywords: cardiovascular events; cardiovascular outcome trial; intensive glucose control; type 2 diabetes mellitus.

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Figures

Figure 1

Figure 1

Meta‐regression analysis between reduction of HbA1c and MACE risk in the 12 CVOTs. CVOT indicates cardiovascular outcome trial; HbA1c, glycated hemoglobin; HR, hazard ratio; MACE, major cardiovascular events.

Figure 2

Figure 2

Meta‐analysis of 5 CVOTs (3 with GLP‐1 RAs and 2 with SGLT‐2i) in patients with history of CVD at baseline. The results are highly homogeneous, as heterogeneity was almost nil and not significant. CVD indicates cardiovascular disease; CVOTs, cardiovascular outcome trials; GLP‐1 RAs, glucagon‐like peptide‐1 receptor agonists; HR, hazard ratio; SGLT‐2i, sodium‐glucose cotransporter 2 inhibitor.

Figure 3

Figure 3

Meta‐analysis of the 5 CVOTs in patients without history of CVD at baseline. The results are highly homogeneous, as heterogeneity was almost nil and not significant. CVD indicates cardiovascular disease; CVOTs, cardiovascular outcome trials; GLP‐1 RAs, glucagon‐like peptide‐1 receptor agonists; HR, hazard ratio; SGLT‐2i, sodium‐glucose cotransporter 2 inhibitor.

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