Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes

Abstract

Background Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs. Methods We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals. Results Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74–1.03) in the target population, compared to 0.86 (0.74–0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77–0.99) in the target population compared to 0.87 (0.78–0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population. Conclusions Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

“…[18][19][20][21][22][23] Additional potential benefits of empagliflozin and other SGLT2 inhibitors include improved cardiovascular energetics, reduced vascular tone and blood pressure, decreased renal dysfunction, increased circulating levels of ketone bodies, protection against pulmonary ischemia/reperfusion injury, and overall reduced systemic inflammation. [24][25][26][27][28][29][30][31][32][33][34][35][36][37] On these grounds, we investigated the effects of empagliflozin on frailty in diabetic and hypertensive older adults. To mechanistically confirm our results, we evaluated the effects of empagliflozin on mitochondrial oxidative stress and permeabilization in human endothelial cells.…”

“…18–23 Additional potential benefits of empagliflozin and other SGLT2 inhibitors include improved cardiovascular energetics, reduced vascular tone and blood pressure, decreased renal dysfunction, increased circulating levels of ketone bodies, protection against pulmonary ischemia/reperfusion injury, and overall reduced systemic inflammation. 24–37…”

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

“…Of note, using the same real-world dataset, there was high heterogeneity between the proportion of patients that could have been included in different trials, emphasizing the problem of generalizability. However, a recent study evaluated the transposition of cardiovascular outcome trial effects to the real-world population using CVOT stratum-specific effects, showing that the cardiovascular benefits are transferable to a much different real-world population [ 49 ].…”

The relationship between HbA1c control pattern and atherosclerosis progression of diabetes: a prospective study of Chinese population

“…Our study determined the causal relationship between glycemic control patterns and atherosclerosis progression; however, we could not give more suggestion about the effects of the new treatments for diabetes. The recent study revealed a decreased risk of coronary heart disease in patients with type 2 diabetes treated with GLP-1 receptor agonists and SGLT2 inhibitors, which provided the idea for our next research [ 29 , 30 ].…”