DYSGLYCEMIA, EJECTION FRACTION, AND THE RISK OF HEART FAILURE OR CARDIOVASCULAR DEATH IN PATIENTS WITH TYPE 2 DIABETES AND A RECENT ACUTE CORONARY SYNDROME

2019 ◽  
Vol 73 (9) ◽  
pp. 773
Author(s):  
Sung-Hee Shin ◽  
Brian Claggett ◽  
Marc Pfeffer ◽  
David Aguilar ◽  
Rafael Diaz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Ejection Fraction ◽  
Cardiovascular Death ◽  
Coronary Syndrome

Apabetalone, a selective BET protein inhibitor, reduces ischemic cardiovascular events and hospitalization for heart failure in patients with acute coronary syndrome and type 2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
S.J Nicholls ◽  
K.A Buhr ◽  
H.N Ginsberg ◽  
K Kalantar-Zadeh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Number Needed To Treat ◽  
Funding Source ◽  
Protein Inhibitor ◽  
Private Company ◽  
Coronary Syndrome ◽  
Bet Protein

Abstract Background Despite established treatments, patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) are at higher risk of ischemic cardiovascular (CV) events and hospitalization for heart failure (HHF) compared to those without T2DM. LDL-C lowering or use of GLP-1 agonists predominantly affects ischemic CV events, with little effect on HHF. Conversely, treatment with SGLT-2 inhibitors reduces HHF, with less effect on ischemic CV events. Preclinical studies indicate that bromodomain and extra-terminal (BET) proteins coordinate gene transcription for pathways that promote atherothrombotic events as well as heart failure. We assessed the clinical effect of apabetalone (APB), a novel BET protein inhibitor, on a composite of non-fatal ischemic CV events, HHF, and CV death in a post hoc analysis of the BETonMACE trial Methods BETonMACE was a double-blind, placebo-controlled phase 3 study in patients with T2DM and recent acute coronary syndrome receiving standard of care risk factor management. In 13 countries, 2425 patients were enrolled. We conducted a time-to-event analysis for first adjudicated CV death or non-fatal MI, stroke, or HHF using a log-rank test and Cox proportional hazards model. Results At baseline median age was 62 years, 25.6% were female, 87.6% white, and use of high intensity statin, ACE inhibitors/ angiotensin II blockers, dual antiplatelet therapy and beta blocker were 90, 88, 92 and 91% respectively. A total of 312 subjects had an endpoint event, with 139 (11.5%) patients in the ABP group and 173 (14.3%) among PBO (HR 0.78, 95% CI 0.63–0.98, p=0.03, Figure). At 26 months, the absolute risk reduction was 3.2% and number needed to treat was 31. Numerically favorable HRs were observed for each component endpoint except for stroke (Table). Conclusion This present analysis suggests that BET inhibition with APB may be a novel pathway through which to reduce both HHF and ischemic CV events in high risk patients with T2DM thus impacting broader clinical outcomes with potentially large benefits for patients and healthcare systems. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Resverlogix Corp

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 Prognostic value of atherogenic index of plasma in patients with type 2 diabetes and acute coronary syndrome

2020 ◽  
Author(s):  
Le Wang ◽  
hongliang cong ◽  
Jingxia Zhang ◽  
Yuecheng Hu ◽  
Ao Wei ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Prognostic Value ◽  
Cardiovascular Death ◽  
Mortality Prediction ◽  
Atherogenic Index ◽  
Coronary Syndrome ◽  
Patients With Diabetes

Abstract Background: Atherogenic index of plasm (AIP) has been identified as a risk factor for cardiovascular disease (CVD) and an independent predictor of mortality. However, it remains unknown whether AIP level may predict mortality in patients with diabetes and acute coronary syndrome (ACS). Methods: A total of 2531 consecutive patients with type 2 diabetes who underwent coronary angiography for ACS were enrolled in the study. Patients were divided into tertiles according to admission AIP level. The AIP was calculated as the base 10 logarithm of the ratio of the fating concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). The primary endpoints were all-cause death and cardiovascular death. Multivariate cox hazard regression analysis were performed to calculate the hazard ratio(HR)and 95％confidence interval(CI)．C-statistics, continuous net reclassification improvement(NRI)，and integrated discrimination improvement(IDI) were calculated to evaluate the added prognostic value of AIP beyond the established mode for prediction of death．Results: During 3-year follow-up, all-cause death events occurred in 142 cases and cardiovascular death events occurred in 120 cases, respectively. The risk of all-cause death and cardiovascular death increased with AIP tertiles at a 3-year follow-up. The Kaplan-Meier curves showed that significant differences in event-free survival rates among AIP tertiles(all-cause mortality: p=0.006; cardiovascular mortality: p=0.003).Multivariate cox hazard regression analysis revealed that AIP was independently associated with all-cause death (HR: 3.859, 95% CI:1.926-7.734; p<0.001) and cardiovascular death (HR:4.723, 95% CI: 2.243-9.946; p<0.001). Addition of AIP to the established mode for mortality prediction was not associated with a significant improvement in the C-statistics value but there were significant improvements in reclassification for all-cause death (NRI: 0.198, p=0.022; IDI: 0.008, p=0.016) and cardiovascular death (NRI: 0.260, p=0.006; IDI: 0.010, p=0.021).Conclusions: Admission AIP was independently correlated with long-term mortality in patients with type 2 diabetes and ACS. These findings suggest that AIP may optimize the mortality prediction among patients with diabetes and ACS.

Comparison of prasugrel and ticagrelor for patient with acute coronary syndrome: a systematic review and meta-analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.C.W Fong ◽  
N Lee ◽  
A.T Yan ◽  
M.Y Ng
Keyword(s):  
Acute Coronary Syndrome ◽  
Stent Thrombosis ◽  
Meta Analysis ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Coronary Syndrome ◽  
Primary Composite Endpoint ◽  
Significant Difference ◽  
St Elevation

Abstract Background Prasugrel and ticagrelor are both effective anti-platelet drugs for patients with acute coronary syndrome. However, there has been limited data on the direct comparison of prasugrel and ticagrelor until the recent ISAR-REACT 5 trial. Purpose To compare the efficacy of prasugrel and ticagrelor in patients with acute coronary syndrome with respect to the primary composite endpoint of myocardial infarction (MI), stroke or cardiac cardiovascular death, and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), and stent thrombosis within 1 year. Methods Meta-analysis was performed on randomised controlled trials (RCT) up to December 2019 that randomised patients with acute coronary syndrome to either prasugrel or ticagrelor. RCTs were identified from Medline, Embase and ClinicalTrials.gov using Cochrane library CENTRAL by 2 independent reviewers with “prasugrel” and “ticagrelor” as search terms. Effect estimates with confidence intervals were generated using the random effects model by extracting outcome data from the RCTs to compare the primary and secondary clinical outcomes. Cochrane risk-of-bias tool for randomised trials (Ver 2.0) was used for assessment of all eligible RCTs. Results 411 reports were screened, and we identified 11 eligible RCTs with 6098 patients randomised to prasugrel (n=3050) or ticagrelor (n=3048). The included trials had a follow up period ranging from 1 day to 1 year. 330 events on the prasugrel arm and 408 events on the ticagrelor arm were recorded. There were some concerns over the integrity of allocation concealment over 7 trials otherwise risk of other bias was minimal. Patients had a mean age of 61±4 (76% male; 50% with ST elevation MI; 35% with non-ST elevation MI; 15% with unstable angina; 25% with diabetes mellitus; 64% with hypertension; 51% with hyperlipidaemia; 42% smokers). There was no significant difference in risk between the prasugrel group and the ticagrelor group on the primary composite endpoint (Figure 1) (Risk Ratio (RR)=1.17; 95% CI=0.97–1.41; p=0.10, I2=0%). There was no significant difference between the use of prasugrel and ticagrelor with respect to MI (RR=1.24; 95% CI=0.81–1.90; p=0.31); stroke (RR=1.05; 95% CI=0.66–1.67; p=0.84); cardiovascular death (RR=1.01; 95% CI=0.75–1.36; p=0.95); BARC type 2 or above bleeding (RR=1.17; 95% CI =0.90–1.54; p=0.24); stent thrombosis (RR=1.58; 95% CI =0.90–2.76; p=0.11). Conclusion Compared with ticagrelor, prasugrel did not reduce the primary composite endpoint of MI, stroke and cardiovascular death within 1 year. There was also no significant difference in the risk of MI, stroke, cardiovascular death, major bleeding and stent thrombosis respectively. Figure 1. Primary Objective Funding Acknowledgement Type of funding source: None

scholarly journals Impact of timing of randomization after an acute coronary syndrome and subsequent events in patients with type 2 diabetes mellitus: an analysis of the EXAMINE trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Elharram ◽  
A Sharma ◽  
W White ◽  
G Bakris ◽  
P Rossignol ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Type 2 Diabetes Mellitus ◽  
Acute Coronary Syndrome ◽  
Primary Outcome ◽  
Funding Source ◽  
Coronary Syndrome ◽  
The Impact

Abstract Background The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes. Methods EXAMINE was a randomized trial of alogliptin versus placebo in 5380 patients with T2DM and a recent ACS. The primary outcome was a composite of CV death, non-fatal myocardial infarction [MI], or non-fatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8–34, 35–56, and 57–141 days. Results Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs. 33.0%), prior coronary artery bypass graft (9.6% vs. 15.9%), or atrial fibrillation (5.9% vs. 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio [aHR] 1.47; 95% CI 1.21–1.74) (Figure 1). Similarly, patients randomized early had an increased risk of recurrent MI (aHR 1.51; 95% CI 1.17–1.96) and HF hospitalization (1.49; 95% CI 1.05–2.10). Conclusion In a contemporary cohort of T2DM with a recent ACS, early randomization following the ACS increases the risk of CV events including recurrent MI and HF hospitalization. This should be taken into account when designing future clinical trials. Figure 1 Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Takeda Pharmaceutical

scholarly journals Benefit and Harm of Extended Dual Antiplatelet Therapy After PCI in high-risk TWILIGHT-like patients with acute coronary syndrome

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
HY Wang ◽  
R Zhang ◽  
ZX Cai ◽  
KF Dou
Keyword(s):  
Acute Coronary Syndrome ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
Short Term ◽  
Bleeding Events ◽  
Coronary Syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following PCI irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients. This study sought to investigate the benefits and risks of extended-term (&gt;12-month) DAPT as compared with short-term DAPT in high-risk "TWILIGHT-like" ACS patients undergoing PCI. Methods All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 to December 2013 were identified from the prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least 1 clinical and 1 angiographic feature based on TWILIGHT trial selection criteria. The present analysis evaluated 4,875 high-risk "TWILIGHT-like" patients with ACS who were event-free at 12 months after PCI. The primary outcome was the composite of all-cause death, myocardial infarction (MI), or stroke at 30 months while BARC type 2, 3, or 5 bleeding was key secondary outcome. Results Extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI, or stroke by 63% (1.5% vs. 3.8%; HRadj: 0.374, 95% CI: 0.256 to 0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007 to 0.362) and that for MI 0.45 (0.153 to 1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9% vs. 1.3%; HRadj: 0.668 [0.379 to 1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly in patients treated with DAPT &gt; 12-month or DAPT ≤ 12-month. The effect of long-term DAPT on primary and key secondary outcome across the proportion of ACS patients with 1-3, 4-5, or 6-9 risk factors showed a consistent manner (Pinteraction &gt; 0.05). Conclusion Among high-risk "TWILIGHT-like" patients with ACS after PCI, long-term DAPT reduced ischemic events without increasing clinically meaningful bleeding events as compared with short-term DAPT, suggesting that extended DAPT might be considered in the treatment of ACS patients who present with a particularly higher risk for thrombotic complications. Abstract Figure.

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