Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

2022 ◽  
Author(s):  
Avivit Cahn ◽  
Stephen D. Wiviott ◽  
Ofri Mosenzon ◽  
Sabina A. Murphy ◽  
Erica L. Goodrich ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Baseline Hba1c ◽  
Renal Outcomes ◽  
Increased Risk ◽  
Hba1c Levels

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

scholarly journals Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

2022 ◽  
Author(s):  
Avivit Cahn ◽  
Stephen D. Wiviott ◽  
Ofri Mosenzon ◽  
Sabina A. Murphy ◽  
Erica L. Goodrich ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Baseline Hba1c ◽  
Renal Outcomes ◽  
Increased Risk ◽  
Hba1c Levels

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

scholarly journals Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

Diabetes Care ◽  
2022 ◽  
Author(s):  
Avivit Cahn ◽  
Stephen D. Wiviott ◽  
Ofri Mosenzon ◽  
Erica L. Goodrich ◽  
Sabina A. Murphy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Baseline Hba1c ◽  
Renal Outcomes ◽  
Increased Risk ◽  
Hba1c Levels

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction &gt; 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c &lt;7%.

Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes

2020 ◽  
Vol 105 (7) ◽  
pp. 2371-2380 ◽  
Author(s):  
Mikael Croyal ◽  
Pierre-Jean Saulnier ◽  
Audrey Aguesse ◽  
Elise Gand ◽  
Stéphanie Ragot ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Tumor Necrosis Factor Receptor ◽  
Density Lipoprotein ◽  
Major Adverse Cardiovascular Events ◽  
Cox Models ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Design And Methods

Abstract Objective Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D). Research Design and Methods We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D. Results The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P &lt; 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514. Conclusions We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.

scholarly journals Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

2021 ◽  
Author(s):  
Frederik Persson ◽  
Stephen C Bain ◽  
Ofri Mosenzon ◽  
Hiddo J.L. Heerspink ◽  
Johannes F. E. Mann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
First Year ◽  
Treatment Groups ◽  
Renal Outcomes ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Design And Methods

<b>OBJECTIVE</b> <p>A <i>post hoc</i> analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years, in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (<i>N</i>=2,928), 30–0% reduction <i>N</i>=1,218) or any increase in UACR (<i>N</i>=4,124) irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes.</p> <p><b>RESULTS</b></p> <p>For MACE, hazard ratios (HRs) for those with >30% and 30%–0% UACR reduction were 0.82 (95% CI 0.71–0.94; <i>P</i>=0.006) and 0.99 (0.82–1.19; <i>P</i>=0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs (95% CI) were 0.67 (0.49–0.93; <i>P</i>=0.02) and 0.97 (0.66–1.43; <i>P</i>=0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. </p> <p><b>CONCLUSIONS</b></p> <p>A reduction in albuminuria during the first year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential. </p>

scholarly journals Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

2021 ◽  
Author(s):  
Frederik Persson ◽  
Stephen C Bain ◽  
Ofri Mosenzon ◽  
Hiddo J.L. Heerspink ◽  
Johannes F. E. Mann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cox Regression ◽  
Major Adverse Cardiovascular Events ◽  
First Year ◽  
Treatment Groups ◽  
Renal Outcomes ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Design And Methods

<b>OBJECTIVE</b> <p>A <i>post hoc</i> analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years, in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (<i>N</i>=2,928), 30–0% reduction <i>N</i>=1,218) or any increase in UACR (<i>N</i>=4,124) irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes.</p> <p><b>RESULTS</b></p> <p>For MACE, hazard ratios (HRs) for those with >30% and 30%–0% UACR reduction were 0.82 (95% CI 0.71–0.94; <i>P</i>=0.006) and 0.99 (0.82–1.19; <i>P</i>=0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs (95% CI) were 0.67 (0.49–0.93; <i>P</i>=0.02) and 0.97 (0.66–1.43; <i>P</i>=0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. </p> <p><b>CONCLUSIONS</b></p> <p>A reduction in albuminuria during the first year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential. </p>

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Empagliflozin and EMPA-REG OUTCOME

2020 ◽  
Vol 20 (2) ◽  
pp. 138-141
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiovascular Outcome Trial

EMPA-REG OUTCOME was an FDA-mandated cardiovascular outcome trial with empagliflozin and was the first completed trial with a sodium-glucose co-transporter-2 (SGLT2) inhibitor. EMPA-REG OUTCOME compared empagliflozin and placebo in 7,020 subjects with type 2 diabetes and established atherosclerotic cardiovascular disease. The results were astounding as EMPA-REG OUTCOME demonstrated superiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was also significantly reduced. Later trials with SGLT2 inhibitors have demonstrated reductions in major adverse cardiovascular events (MACE) and hospitalisation for heart failure, and trials with glucagon-like peptide 1 receptor agonists have demonstrated reductions in MACE. Collectively, these trials could transform the management of people with type 2 diabetes.

scholarly journals HbA1c Evidence for a Prediabetes Diagnosis Delays Onset of Type 2 Diabetes

2021 ◽  
Vol 3 (1) ◽  
pp. 1-15
Author(s):  
Maurice Johnson ◽  
Howard Fishbein ◽  
Rebecca Jeffries Birch ◽  
Qilu Yu ◽  
Russ Mardon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Logistic Regression ◽  
Hba1c Level ◽  
Cox Regression ◽  
Cox Model ◽  
Diabetes Research ◽  
Baseline Hba1c ◽  
Multivariable Logistic Regression Model ◽  
Hba1c Levels

Objective: This study examined the influential role of making a prediabetes diagnosis resulting in the subsequent delay in onset of type 2 diabetes. Research Design and Methods: Using electronic medical records, a multivariable logistic regression model examined demographic and clinical risk factors associated with a prediabetes diagnosis among patients with HbA1c evidence of prediabetes. A multivariable non-proportional Cox regression examined development to type 2 diabetes (maximum 7 year follow-up). Results: Analysis includes 40,970 patients with incident prediabetes (76.8% undiagnosed). Logistic regression showed higher baseline HbA1c levels significantly influenced assigning a prediabetes diagnosis: compared to patients with HbA1c level 5.7-5.9% (low), OR 1.66 (99% CI 1.54-1.78) for HbA1c level 6.0-6.2% (medium) and OR 1.62 (CI 1.43-1.83) for HbA1c level 6.3-6.4% (high). Cox model results, which included an interaction between HbA1c and prediabetes diagnosis, found HbA1c the most significant predictor. Patients with diagnosed prediabetes progressed to type 2 diabetes slower than those undiagnosed. Comparing diagnosed patients to undiagnosed within the same HbA1c level, HRs ranged from 0.47 (CI 0.37-0.61) in the high HbA1c level to 0.83 (CI 0.67-1.02) in the low HbA1c level. Conclusions: From the LEADR cohort (1) HbA1c levels were the principle factor associated with risk for prediabetes diagnosis. Modeling development to diabetes, baseline HbA1c was the significant predictor of risk. Findings suggest assignment of a prediabetes diagnosis is associated with slower development of diabetes and this protective benefit of being diagnosed increases with a higher baseline HbA1c. Prediabetes diagnosis is useful for delaying onset of type 2 diabetes.

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