scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Lixisenatide and ELIXA

2020 ◽  
Vol 20 (1) ◽  
pp. 52-54
Author(s):  
Miles Fisher
Keyword(s):  
Myocardial Infarction ◽  
Unstable Angina ◽  
Cardiovascular Events ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Receptor Agonists ◽  
Coronary Syndrome ◽  
Cardiovascular Outcome Trial

ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) was an FDA mandated cardiovascular outcome trial with lixisenatide. In contrast to later cardiovascular outcome trials with glucagon-like peptide-1 (GLP-1) receptor agonists, it was performed in subjects with a recent myocardial infarction or hospitalisation for unstable angina within the previous 180 days. ELIXA compared lixisenatide and placebo in 6,068 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events plus unstable angina (cardiovascular death, myocardial infarction, stroke, unstable angina) but not superiority. Similarly, there was no difference in hospitalisation for heart failure which was a secondary outcome. A subsequent exploratory analysis showed that lixisenatide reduced progression of the urinary albumin to creatinine ratio in patients with macroalbuminuria, and was associated with a lower risk of new-onset macroalbuminuria. No clear clinical benefit has been established for lixisenatide, and there are alternative GLP-1 receptor agonists such as liraglutide, semaglutide and dulaglutide that are associated with a reduction in major adverse cardiovascular events.

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Liraglutide and LEADER

2020 ◽  
Vol 20 (2) ◽  
pp. 142-144
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial

LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) was an FDA-mandated cardiovascular outcome trial with liraglutide and was the first trial with a glucagon-like peptide-1 (GLP-1) receptor agonist to demonstrate a significant reduction in cardiovascular events. It compared liraglutide and placebo in 9,340 people with type 2 diabetes and either existing cardiovascular disease or age >60 years with at least one cardiovascular risk factor. LEADER demonstrated superiority for major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was not significantly reduced. Compared with the EMPA-REG OUTCOME trial, the curves for major adverse cardiovascular events in LEADER separated later, and the absence of a clear effect on hospitalisation for heart failure or on estimated glomerular filtration rate suggests that the mechanism of cardiovascular benefit for liraglutide was different from that for empagliflozin

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Sitagliptin and TECOS

2020 ◽  
Vol 20 (1) ◽  
pp. 55-57
Author(s):  
Miles Fisher
Keyword(s):  
Unstable Angina ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Clinical Role ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial

TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) was an investigator-initiated cardiovascular outcome trial with sitagliptin. It compared sitagliptin and placebo in 14,671 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events plus hospitalisation for unstable angina (cardiovascular death, myocardial infarction, stroke, unstable angina) but not superiority. Rates of hospitalisation for heart failure did not differ between the sitagliptin and placebo groups, and there were no significant between-group differences in rates of acute pancreatitis or pancreatic cancer. The clinical role for dipeptidyl peptidase-4 (DPP-4) inhibitors is diminishing as they have not been demonstrated to reduce cardiovascular events and are not associated with weight reduction, but if a DPP-4 inhibitor is indicated, the results of TECOS show that sitagliptin appears safer than saxagliptin or alogliptin.

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.

4113Glucose lowering drugs or strategies, major adverse cardiovascular events and heart failure outcomes, and association with weight loss - meta-analysis of large cardiovascular outcome trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O R Ghosh-Swaby ◽  
S G Goodman ◽  
L A Leiter ◽  
A Cheng ◽  
K Connelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Loss ◽  
Risk Reduction ◽  
Cardiovascular Events ◽  
Cardiovascular Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Risk Reduction ◽  
Cardiovascular Outcome Trials ◽  
Lower Weight ◽  
Meta Regression

Abstract Background Glucose lowering drugs or strategies (GLDS) have varied effects on major adverse cardiovascular events (MACE) and heart failure (HF) in cardiovascular outcomes trials. Mechanisms driving cardiovascular risk reduction remain elusive. Methods We searched MEDLINE, PubMed, and meeting abstracts up to 11/21/2018 for large GLDS cardiovascular outcome trials (CVOTs) in patients with or at risk for type 2 diabetes. Primary endpoints of MACE and HF were evaluated with random effects risk ratios (RR) and explored by baseline CVD subgroups and meta-regression by weight change across treatment arms. Results In 27 GLDS CVOTs, a total 207,820 patients, median age 63 years, 64% male, 64% CVD and 11% with prior HF were studied over a mean 3.8 years with 20,118 (10%) patients having MACE and 7,212 (4%) a HF event. Compared with standard care, GLDS overall lowered MACE (RR 0.92, P<0.ehz745.01171) but not HF (RR 1.01, P=0.91). Across GLDS, the magnitude and directionality varied modestly for MACE RR (P-int=0.07) but markedly for HF (P-int<0.ehz745.01171). Meta-regression showed a change in HF RR by 6% (95% CI 3%-9%) per 1 kg weight gain/loss between treatment arms (P=0.0006; Figure). In 9 trials of GLDS that achieved marked weight loss (lifestyle, GLP1 agonists, SGLT2 inhibitors), MACE benefit was confined to patients with baseline CVD (RR 0.89 [0.84–0.95] versus without (RR 1.02 [0.91–1.15]; P-int=0.01) with consistent HF effect (RR 0.80 [0.72–0.88] vs RR 0.76 [0.56–1.03]; P-int=0.74). Heart Failure Risk and Changes in Weight Conclusion HF outcomes were improved with GLDS that lower weight. Among diabetes GLDS that lower weight, there was a robust risk reduction in atherothrombotic and heart failure events, with the MACE benefit confined to patients with established CVD. Acknowledgement/Funding Heart and Stroke Foundation

scholarly journals Impact of type 2 diabetes mellitus and blood glucose admission levels in patients with myocardial infarction with non obstructive coronary artery disease (MINOCA)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Paolisso ◽  
F Donati ◽  
L Bergamaschi ◽  
S Toniolo ◽  
E.C D'Angelo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Independent Predictor ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome ◽  
Type 2 Dm ◽  
All Cause Mortality ◽  
Age And Sex

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinically entity and represents 5% to 10% of all patients with myocardial infarction (MI). Besides type 2 diabetes mellitus (DM), which is a common comorbidity in patients hospitalized for an acute coronary syndrome, high glucose levels (HGL) at admission are frequently observed in this context. The risk of major adverse cardiovascular events following acute coronary syndrome is increased in people with DM and HGL. However, evidence regarding diabetes and high glucose level among MINOCA patients is lacking. Purpose To examine the incidence of major adverse cardiovascular events (MACEs) in diabetic and non-diabetic MINOCA patients as well as according to HGL at presentation. Methods Among 1995 patients with acute MI admitted to our coronary care unit from 2016 to 2018, we enrolled 186 consecutive MINOCA patients according to the current ESC diagnostic criteria. HGL at admission was defined as serum glucose level above 180 mg/dl. All-cause mortality and a composite end-point of all-cause mortality and myocardial re-infarction were compared. The median follow-up time was 19.6±12.9 months. Results Diabetic MINOCA patients were older (mean age 75.5±9.6 vs 66.5±14.7; p=0.002) and with higher prevalence of hypertension (p=0.016). Conversely, there were no significant differences in gender, BMI, dyslipidemia and atrial fibrillation. Similarly, no significant differences were observed regarding clinical and ECG presentation, echocardiographic features and laboratory tests. The rates of death (30.8% vs 8.3%; p=0.013) and MACEs (22.2% vs 6.8%; p=0.025) were significantly higher in MINOCA-DM patients; conversely, no significant differences were observed for re-MI (p=0.58). At multivariate regression model adjusted for age and sex, type 2 DM was not an independent predictor of all cause deaths (p=0.36) and MACE (p=0.24). Patients with admission HGL had similar baseline characteristics, cardiovascular risk factors, clinical presentations, echocardiographic features and troponin values as compared to patients with no-HGL. HGL at admission was associated with higher incidence of all-cause-death (p&lt;0.001) and MACE (p=0.003) during follow-up compared to patients with no HGL; conversely, no significant differences were observed in the incidence of re-MI (p=0.7). Multivariate analysis adjusted for age and sex demonstrated that HGL was an independent predictor of death (HR 6.25; CI 1.64–23.85; p=0.007) and MACEs (HR 6.17; CI 1.79–21.23, p=0.004). Conclusion In MINOCA patients, HGL was an independent risk factor for both MACEs and death while type 2 DM was not correlated with these hard endpoints. As a consequence, HGL could have a still unexplored pathophysiological role in MINOCA. Properly powered randomized trials are warranted. Funding Acknowledgement Type of funding source: None

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Alogliptin and EXAMINE

2019 ◽  
Vol 19 (2) ◽  
pp. 133-135
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Coronary Syndrome ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Subsequent Publication ◽  
Outcome Trial

EXAMINE was an FDA mandated cardiovascular outcome trial with alogliptin. In contrast to other cardiovascular outcome trials with DPP-4 inhibitors, it was performed in subjects with a recent acute coronary syndrome. EXAMINE compared alogliptin and placebo in 5,380 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. Data on hospitalisation for heart failure were not included in the principal publication. A subsequent publication showed no overall increase in hospitalisation for heart failure with alogliptin, but when subjects with and without baseline heart failure were separated there was a significant increase in the group without heart failure at baseline. No clear clinical benefit has been established for alogliptin, and there are alternatives such as sitagliptin and linagliptin that are not associated with an increase in hospitalisation for heart failure.

scholarly journals Efficacy and safety of high-dose Xueshuantong injection (lyophilised) in reducing the incidence of major adverse cardiovascular events in patients with unstable angina: a protocol of a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial based on dual antiplatelet therapy

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e038074
Author(s):  
Wenjie Long ◽  
Huili Liao ◽  
Xi Huang ◽  
Qingqing Liu ◽  
Yaqing Tang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Coronary Syndrome ◽  
Unstable Angina ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Multicentre Clinical Trial ◽  
Coronary Syndrome ◽  
Link Type

IntroductionUnstable angina (UA), referred to as acute coronary syndrome (ACS), causes unexpected chest pain. Xueshuantong injection (lyophilised) (XST) is a traditional Chinese herbal injection having the potential to treat ACS. However, no clinical trial has been performed in this field. This clinical trial aims to examine the efficacy and safety of XST.Methods and analysisThis is a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial. A total of 1200 participants with UA will be enrolled in a 1:1 ratio, with 600 patients included in the XST treatment group and 600 with 1/20th dose in the control group. The efficacy assessment and major adverse cardiovascular events will be observed, and the frequency of angina attack, angina pectoris will be examined at the start and end of the run-in period. All adverse events will be recorded, regardless of the severity, to assess the safety of XST. The baseline characteristics of patients will be summarised and compared using the t test or non-parametric statistical test. Qualitative data will be analysed using the χ2 or Fisher exact tests, Cochran–Mantel–Hasenszel test and Wilcoxon test.Ethics and disseminationThis trial has been approved by the Research Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2017] 0021). Written informed consent will be obtained from all participants. The results of this trial will be disseminated to the public through academic conferences and peer-reviewed journals.Trial registrationThis study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the ID ChiCTR1800015911.

scholarly journals Prasugrel or ticagrelor in patients with acute coronary syndrome and diabetes: a propensity matched substudy of RENAMI

2018 ◽  
Vol 8 (6) ◽  
pp. 536-542 ◽  
Author(s):  
Federico Conrotto ◽  
Maurizio Bertaina ◽  
Sergio Raposeiras-Roubin ◽  
Tim Kinnaird ◽  
Albert Ariza-Solé ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Primary Endpoints ◽  
Diabetes Patients

Introduction: The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed. Methods: All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3–5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints. Results: Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%, P=0.16 and 6.7% vs. 4.1%, P=0.11, respectively). Ticagrelor was associated with a lower risk of death and BARC 2–5 bleeding when compared to prasugrel (2.8% vs. 0.8%, P=0.031 and 6.0% vs. 2.6%, P=0.02, respectively) and a clear but not significant trend for a reduction of BARC 3–5 bleeding (2.3% vs. 0.8%, P=0.08). There were no significant differences in myocardial infarction recurrence and stent thrombosis. Conclusion: Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

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