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.
Figures
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
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
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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References
- Rawshani A, Rawshani A, Franzén S, Sattar N, Eliasson B, Svensson AM, Zethelius B, Miftaraj M, McGuire DK, Rosengren A, Gudbjörnsdottir S. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018;379:633–644. - PubMed
- Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L. Changes in diabetes‐related complications in the United States, 1990–2010. N Engl J Med. 2014;370:1514–1523. - PubMed
- Olesen KKW, Madsen M, Egholm G, Thim T1, Jensen LO, Raungaard B, Bøtker HE, Sørensen HT, Maeng M. Patients with and without diabetes without significant angiographic coronary artery disease have the same risk of myocardial infarction in a real‐world population receiving appropriate prophylactic treatment. Diabetes Care. 2017;40:1103–1110. - PubMed
- Pagidipati NJ, Navar AM, Pieper KS, Green JB, Bethel MA, Armstrong PW, Josse RG, McGuire DK, Lokhnygina Y, Cornel JH, Halvorsen S, Strandberg TE, Delibasi T, Holman RR, Peterson ED; TECOS Study Group . Secondary prevention of cardiovascular disease in patients with type 2 diabetes: international insights from the TECOS trial. Circulation. 2017;136:1193–1203. - PMC - PubMed
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