scholarly journals Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes

JAMA ◽  
2020 ◽  
Vol 323 (16) ◽  
pp. 1565 ◽  
Author(s):  
Kausik K. Ray ◽  
Stephen J. Nicholls ◽  
Kevin A. Buhr ◽  
Henry N. Ginsberg ◽  
Jan O. Johansson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Standard Therapy ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome

scholarly journals Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With Diabetes and Acute Coronary Syndrome

2018 ◽  
Vol 103 (7) ◽  
pp. 2522-2533 ◽  
Author(s):  
Barbara E Stähli ◽  
Anna Nozza ◽  
Ilse C Schrieks ◽  
John B Buse ◽  
Klas Malmberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Risk Of Death ◽  
Coronary Syndrome

Abstract Objective Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain. Design The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events. Conclusions After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.

scholarly journals Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome

2021 ◽  
pp. CJN.16751020
Author(s):  
Kamyar Kalantar-Zadeh ◽  
Gregory G. Schwartz ◽  
Stephen J. Nicholls ◽  
Kevin A. Buhr ◽  
Henry N. Ginsberg ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Adverse Events ◽  
Confidence Interval ◽  
Cardiovascular Events ◽  
Hazard Ratio ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome

Background and objectivesCKD and type 2 diabetes mellitus interact to increase the risk of major adverse cardiovascular events (i.e., cardiovascular death, nonfatal myocardial infarction, or stroke) and congestive heart failure. A maladaptive epigenetic response may be a cardiovascular risk driver and amenable to modification with apabetalone, a selective modulator of the bromodomain and extraterminal domain transcription system. We examined this question in a prespecified analysis of BETonMACE, a phase 3 trial.Design, setting, participants, & measurementsBETonMACE was an event-driven, randomized, double-blind, placebo-controlled trial comparing effects of apabetalone versus placebo on major adverse cardiovascular events and heart failure hospitalizations in 2425 participants with type 2 diabetes and a recent acute coronary syndrome, including 288 participants with CKD with eGFR <60 ml/min per 1.73 m2 at baseline. The primary end point in BETonMACE was the time to the first major adverse cardiovascular event, with a secondary end point of time to hospitalization for heart failure.ResultsMedian follow-up was 27 months (interquartile range, 20–32 months). In participants with CKD, apabetalone compared with placebo was associated with fewer major adverse cardiovascular events (13 events in 124 patients [11%] versus 35 events in 164 patients [21%]; hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.96) and fewer heart failure–related hospitalizations (three hospitalizations in 124 patients [3%] versus 14 hospitalizations in 164 patients [9%]; hazard ratio, 0.48; 95% confidence interval, 0.26 to 0.86). In the non-CKD group, the corresponding hazard ratio values were 0.96 (95% confidence interval, 0.74 to 1.24) for major adverse cardiovascular events, and 0.76 (95% confidence interval, 0.46 to 1.27) for heart failure–related hospitalization. Interaction of CKD on treatment effect was P=0.03 for major adverse cardiovascular events, and P=0.12 for heart failure–related hospitalization. Participants with CKD showed similar numbers of adverse events, regardless of randomization to apabetalone or placebo (119 [73%] versus 88 [71%] patients), and there were fewer serious adverse events (29% versus 43%; P=0.02) in the apabetalone group.ConclusionsApabetalone may reduce the incidence of major adverse cardiovascular events in patients with CKD and type 2 diabetes who have a high burden of cardiovascular disease.

scholarly journals INSULIN, LIXISENATIDE, AND RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES AND A RECENT ACUTE CORONARY SYNDROME

2020 ◽  
Vol 75 (11) ◽  
pp. 94
Author(s):  
David Aguilar ◽  
Marc A. Pfeffer ◽  
Brian Claggett ◽  
Jiankang Liu ◽  
John McMurray ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Coronary Syndrome

scholarly journals Total cardiovascular events analysis of the EXAMINE trial in patients with type 2 diabetes and recent acute coronary syndrome

2018 ◽  
Vol 41 (8) ◽  
pp. 1022-1027 ◽  
Author(s):  
Matthew A. Cavender ◽  
William B. White ◽  
Yuyin Liu ◽  
Joseph M. Massaro ◽  
Richard M. Bergenstal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Coronary Syndrome

scholarly journals Prediction of the long-term risk of adverse cardiovascular events after an episode of acute coronary syndrome in patients with type 2 diabetes

2020 ◽  
Vol 19 (3) ◽  
pp. 2357
Author(s):  
E. A. Nikitina ◽  
I. S. Meletev ◽  
O. V. Soloviev ◽  
E. N. Chicherina
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Logit Model ◽  
Diagnostic Tests ◽  
Cardiovascular Events ◽  
Surgical Revascularization ◽  
Factors Associated ◽  
Coronary Syndrome

Aim. To determine independent predictors of adverse cardiovascular events (ACE) and to develop a long-term (12 months) prognostic model after an episode of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D).Material and methods. The study included 120 T2D patients hospitalized due to ACS in the period from January 2016 to February 2017. All patients underwent standard diagnostic tests. Twelve months after ACS, the incidence of ACE in T2D patients was assessed: cardiovascular mortality, myocardial infarction, emergency surgical revascularization. Additionally, we analyzed composite endpoint (CEP), including all of the adverse outcomes listed. Patients were divided into 2 groups: group 1 (n=34) — patients with ACE; group 2 (n=86) — patients without ACE. Factors associated with the CEP were then included in the logistic regression to determine independent predictors of ACE. In order to predict the development of CEP in patients with ACS and T2D, a logit model was created. To process the model, a ROC analysis was performed.Results. Independent factors associated with ACE for 12 months in T2D patients after an ACS were established: MI of moderate severity (D.M. Aronov classification); hypertriglyceridemia; decreased heart rate variability (SDNN <0 ms); segments with significant coronary stenosis in the amount of ≥3; no surgical revascularization during acute MI. Based on independent factors, a logit model was developed for assessing 12-month risk of ACE in T2D patients after an ACS.Conclusion. The developed risk prediction model for T2D patients after ACS, based on accessible diagnostic tests, allows to determine the probability of ACE within 12 months.

Abstract 14307: Reduction in the Risk of Major Adverse Cardiovascular Events With Apabetalone, a Bet Protein Inhibitor, in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes According to Insulin Treatment: Analysis of the Betonmace Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gregory G Schwartz ◽  
Stephen J Nicholls ◽  
Henry Ginsberg ◽  
Jan JOHANSSON ◽  
Kamyar Kalantar-Zadeh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
High Risk ◽  
Insulin Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Relative Reduction ◽  
Coronary Syndrome ◽  
Absolute Reduction ◽  
Insulin Use

Introduction: Use of insulin has been associated with worse CV outcomes in patients (pts) with type 2 diabetes T2D. Apabetalone (APB) is a novel selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. In the Phase 3 BETonMACE trial treatment with APB, compared with placebo, resulted in non-significantly fewer major adverse CV events (MACE: CV death, non-fatal MI or stroke) in 2425 pts with T2D and recent acute coronary syndrome (ACS). Objective: In this analysis of BETonMACE we examined the relationship of insulin use to MACE risk and its modification by APB. Methods: Baseline characteristics were compared in insulin-treated (INS) or not insulin-treated (no-INS) pts. The incidence of MACE and treatment hazard ratio (HR) were compared between these two subgroups. Results: 829 (34.2%) pts received insulin at baseline, with or without other diabetes drugs. INS vs no-INS pts were more likely to be female (29 vs 24%), had longer duration of T2D (12.6 vs 6.4 yrs), higher HbA1c (8.4 vs 6.9%) and baseline glucose (156 vs 126 mg/dL), lower use of metformin (73 vs 87%) and sulfonylureas (21 vs 33 %), and higher use of SGLT2 inhibitors (16 vs 6%) and GLP1 receptor agonists (10 vs 2%). MACE in the placebo group was higher in INS than no-INS (17.4% vs 9.7%; HR 1.94; 95% CI 1.39-2.73; p=0.0001). Overall, APB was associated with fewer MACE (HR 0.82, 95% CI 0.65-1.04, p=0.11). The relative reduction in MACE with ABP was similar in INS (HR 0.78, 95% CI. 0.55-1.10, p=0.16) and no-INS (HR 0.87, 95% CI 0.63-1.21, p = 0.42, p interaction =0.64). The absolute reduction in MACE with APB was numerically greater among INS than non-INS (3.69 vs 1.30%). Conclusions: Pts with T2D and recent ACS treated with insulin are at high risk for MACE. High risk of MACE with insulin use is likely through association with other clinical characteristics prognostic for MACE. Insulin treatment may be a marker to identify pts with potential for large absolute reduction in MACE with APB.

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