Lesser effects of SGLT2 inhibition on intermediate markers of cardiovascular risk, such as glycosylated hemoglobin and body weight, are established among patients with reduced eGFR21 and could reduce the magnitude of cardiovascular protection afforded

Lesser effects of SGLT2 inhibition on intermediate markers of cardiovascular risk, such as glycosylated hemoglobin and body weight, are established among patients with reduced eGFR21 and could reduce the magnitude of cardiovascular protection afforded. rate 60?mL/min per 1.73?m2) and without (estimated glomerular filtration rate 60?mL/min per 1.73?m2) reduced kidney function at baseline, for each included study. Figure?S3C. Effects of SGLT2 inhibition on non\fatal MI and stroke for patients with (estimated glomerular filtration rate 60?mL/min per 1.73?m2) and without (estimated glomerular filtration rate 60?mL/min per 1.73?m2) reduced kidney function at baseline, for each included study. Figure?S4A. Effects of SGLT2 inhibition on MACE, CV death, total MI and total stroke for patients with and without a history of heart failure at baseline, for each included study. Figure?S4B. Effects of SGLT2 inhibition on HF hospitalization, CV death/HF hospitalization and all cause mortality for patients with and without a history of heart failure at baseline, for each included study. Figure?S4C. Effects of SGLT2 inhibition on non\fatal MI and stroke for patients with and without a history of heart failure at baseline, for each included study. Figure?S5. Sensitivity analysis for the outcome of serious adverse events without inclusion of risk ratios. Figure?S6. The effects of SGLT2 inhibition on major adverse cardiac outcomes for patients depending on urine albumin creatinine ratio at baseline. JAH3-9-e014908-s001.pdf (5.6M) GUID:?8AD3B99D-5E57-496A-BE10-F76265E8E64E Abstract Background Several trials have demonstrated protective effects from inhibition of sodium\glucose cotransporter 2 among patients with type 2 diabetes mellitus. There is uncertainty about the consistency of the cardiovascular benefits achieved across patient subsets. Methods and Results We included 4 large\scale trials of sodium\glucose cotransporter 2 inhibition compared with placebo in patients with diabetes mellitus that reported effects on cardiovascular outcomes overall and for participant subgroups defined at baseline by cardiovascular disease, reduced kidney function, and heart failure. Fixed effects models with inverse variance weighting were used to estimate summary hazard ratios and 95% CIs. There were 38?723 patients from 4 trials, with a mean 2.9?years of follow\up. Of the patients, 22?870 (59%) had cardiovascular disease, 7754 (20%) had reduced kidney function, and 4543 (12%) had heart failure. There were 3828 major adverse cardiac events. There was overall benefit for major adverse cardiac events (0.88; 95% CI, 0.82C0.94; interaction 0.252; I2 25%). All patient subgroups benefited with respect to hospitalization for heart failure (all interaction 0.302; I2 10%), cardiovascular death (all interaction 0.167; I2 50%), and death from any cause (all interaction 0.354; I2=0%). The only difference in effects across subgroups was for stroke, with protection observed among those with reduced kidney function but not those with preserved kidney function (interaction=0.020; I2=81%). Conclusions Sodium\glucose cotransporter 2 inhibitors protect against cardiovascular disease and death in diverse subsets of patients with type 2 diabetes mellitus regardless of cardiovascular disease history. value for heterogeneity. An I2 statistic of 0% to 25% Rabbit Polyclonal to NDUFA3 was considered to reflect a low likelihood; 26% to 75%, a moderate likelihood; and 76% to 100%, a high likelihood of differences beyond chance. for interaction=0.477). There was an overall 17% relative reduction in cardiovascular death (HR, 0.83; 95% CI, 0.75C0.92), with moderate heterogeneity in effects across the 4 studies (I2=70.7%; for interaction=0.017). SGLT2 inhibition reduced the risk of myocardial infarction (HR, 0.88; 95% CI, 0.80C0.97; I2=0%; for interaction=0.785). With respect to HF outcomes, there was a 32% proportional reduction in hospitalization for HF for those treated with an SGLT2 inhibitor compared with placebo (HR, 0.68; 95% CI, 0.60C0.76) with no evidence of heterogeneity between studies (I2=0; for connection=0.720) and a 24% reduction in the composite end point of cardiovascular death and hospitalization for HF (HR, 0.76; 95% CI, 0.70C0.82). There was moderate heterogeneity between studies within the magnitude of the relative effect for this composite end point (I2=41.9; for connection=0.160). All\cause mortality was also reduced (HR, 0.85; 95% CI, 0.79C0.92), with some evidence of heterogeneity between the trials (We2=63.1%; for connection=0.044) (Number?1 and Number?S2). Open in a separate window Number 1 Effects of sodium\glucose cotransporter 2 inhibition on death and cause\specific cardiovascular (CV) events for individuals with (secondary prevention) and without (main prevention) CV disease at baseline. HF shows heart failure; MACE, major adverse cardiac event. A level of sensitivity analysis was performed excluding the EMPA\REG End result trial to explore the effect of the outlying large reduction in cardiovascular death observed in that trial within the heterogeneity between study findings. Heterogeneity between the remaining studies was much reduced, with I2 ideals for all results reduced to 20% and all.*Indicates subgroup event figures not available for Empagliflozin Cardiovascular End result Event Trial in Type 2 diabetes Mellitus Individuals (EMPA\REG End result). There were 4543 patients Teglarinad chloride (12%) with a history of HF at baseline. rate 60?mL/min per 1.73?m2) and without (estimated glomerular filtration rate 60?mL/min per 1.73?m2) reduced kidney function at baseline, for each included study. Figure?S4A. Effects of SGLT2 inhibition on MACE, CV death, total MI and total stroke for individuals with and without a history of heart failure at baseline, for each included study. Figure?S4B. Effects of SGLT2 inhibition on HF hospitalization, CV death/HF hospitalization and all cause mortality for individuals with and without a history of heart failure at baseline, for each included study. Figure?S4C. Effects of SGLT2 inhibition on non\fatal MI and stroke for individuals with and without a history of heart failure at baseline, for each included study. Figure?S5. Level of sensitivity analysis for the outcome of serious adverse events without inclusion of risk ratios. Number?S6. The effects of SGLT2 inhibition on major adverse cardiac results for individuals depending on Teglarinad chloride urine albumin creatinine percentage at baseline. JAH3-9-e014908-s001.pdf (5.6M) GUID:?8AD3B99D-5E57-496A-BE10-F76265E8E64E Abstract Background Several tests have demonstrated protecting effects from inhibition of sodium\glucose cotransporter 2 among patients with type 2 diabetes mellitus. There is uncertainty about the regularity of the cardiovascular benefits accomplished across patient subsets. Methods and Results We included 4 large\scale tests of sodium\glucose cotransporter 2 inhibition compared with placebo in individuals with diabetes mellitus that reported effects on cardiovascular results overall and for participant subgroups defined at baseline by cardiovascular disease, reduced kidney function, and heart failure. Fixed effects models with inverse variance weighting were used to estimate summary risk ratios and 95% CIs. There were 38?723 individuals from 4 tests, having a mean 2.9?years of follow\up. Of the individuals, 22?870 (59%) had cardiovascular disease, 7754 (20%) had reduced kidney function, and 4543 (12%) had heart failure. There were 3828 major adverse cardiac events. There was overall benefit for major adverse cardiac events (0.88; 95% CI, 0.82C0.94; connection 0.252; I2 25%). All individual subgroups benefited with respect to hospitalization for heart failure (all connection 0.302; I2 10%), cardiovascular death (all connection 0.167; I2 50%), and death from any cause (all connection 0.354; I2=0%). The only difference in effects across subgroups was for stroke, with protection observed among those with reduced kidney function but not those with maintained kidney function (connection=0.020; I2=81%). Conclusions Sodium\glucose cotransporter 2 inhibitors protect against cardiovascular disease and death in varied subsets of individuals with type 2 diabetes mellitus no matter cardiovascular disease history. value for heterogeneity. An I2 statistic of 0% to 25% was considered to reflect a low probability; 26% to 75%, a moderate likelihood; and 76% to 100%, a high likelihood of variations beyond opportunity. for connection=0.477). There was an overall 17% relative reduction in cardiovascular death (HR, 0.83; 95% CI, 0.75C0.92), with moderate heterogeneity in effects across the 4 studies (We2=70.7%; for connection=0.017). SGLT2 inhibition reduced the risk of myocardial infarction (HR, 0.88; 95% CI, 0.80C0.97; I2=0%; for connection=0.785). With respect to HF outcomes, there was a 32% proportional reduction in hospitalization for HF for those treated with an SGLT2 inhibitor compared with placebo (HR, 0.68; 95% CI, 0.60C0.76) with no evidence of heterogeneity between studies (I2=0; for connection=0.720) and a 24% reduction in the composite end point of cardiovascular death and hospitalization for HF (HR, 0.76; 95% CI, 0.70C0.82). There was moderate heterogeneity between studies Teglarinad chloride within the magnitude of the relative effect for this composite end point (I2=41.9; for connection=0.160). All\cause mortality was also reduced (HR, 0.85; 95% CI, 0.79C0.92), with some evidence of heterogeneity between the trials (We2=63.1%; for connection=0.044) (Number?1 and Number?S2). Open in a separate window Number 1 Effects of sodium\glucose cotransporter 2 inhibition on death and cause\specific cardiovascular (CV) events for individuals with (secondary prevention) and without (main prevention) CV disease at baseline. HF shows heart failure; MACE, major adverse cardiac event. A level of sensitivity analysis was performed excluding the EMPA\REG End result trial to explore the effect of the outlying large reduction in cardiovascular death observed in that trial around the heterogeneity between study findings. Heterogeneity between the remaining studies was much reduced, with I2 values for all outcomes reduced to 20% and all corresponding values for interaction being 0.312. A further analysis.