scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Canagliflozin and the CANVAS Program, dapagliflozin and DECLARE-TIMI 58, ertugliflozin and VERTIS CV

2021 ◽  
Author(s):  
Miles Fisher
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Integrated Analysis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiovascular Outcome Trials ◽  
Significant Difference

EMPA-REG OUTCOME was a landmark trial with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) driven by reductions in cardiovascular deaths and accompanied by an early reduction in hospitalisation for heart failure. This was followed by cardiovascular outcome trials with canagliflozin, dapagliflozin and ertugliflozin. The CANVAS Program was an integrated analysis of the CANVAS and CANVAS-R trials with canagliflozin. It demonstrated a significant reduction in MACE, but not in any of the components, and there was an unexpected increase in amputations and fractures with canagliflozin. The DECLARE-TIMI 58 trial with dapagliflozin had two co-primary endpoints. A composite endpoint of cardiovascular death or hospitalisation for heart failure was significantly reduced, but there was no significant difference in MACE comparing dapagliflozin with placebo. Analysis of patients with a prior myocardial infarction, however, demonstrated significant reductions in MACE. The VERTIS CV trial with ertugliflozin was disappointing as there was no difference in MACE comparing ertugliflozin and placebo. In all four trials a reduction in hospitalisation for heart failure was observed in patients with type 2 diabetes, regardless of whether they had existing atherosclerotic cardiovascular disease or increased cardiovascular risk. Pre-specified renal outcomes were reduced with empagliflozin, canagliflozin and dapagliflozin, and these drugs are now commonly used in the management of people with type 2 diabetes. It is hard to envisage an ongoing role for ertugliflozin in routine clinical management as the evidence for its cardiovascular benefit is not convincing.

Abstract P023: Relationship Between Vitamin D Status and Incidence of Macro-vascular Events in the Veterans Affairs Diabetes Trial (VADT)

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jimmy D Alele ◽  
Kelly J Hunt ◽  
Bruce W Hollis ◽  
Deirdre K Luttrell ◽  
Louis M Luttrell ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Veterans Affairs ◽  
Vitamin D Status ◽  
Primary Composite Endpoint

BACKGROUND: Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized type 2 diabetes cohorts. METHODS: We performed prospective analyses to determine associations between vitamin D status and vascular endpoints among 936 Veterans Affairs Diabetes Trial (VADT) participants (mean age 59.7 years; 96.7% male; 40.4% minority). 25 (OH)-vitamin D was measured a median of two years after entry into the VADT study and participants were subsequently followed an average of 3.7 years for outcomes. Cox proportional hazard models were used to calculate hazard ratios (HRs) for macrovascular endpoints in relation to vitamin D quartile. The primary composite endpoint included documented myocardial infarction; stroke; death from cardiovascular causes; new or worsening congestive heart failure; surgical intervention for cardiac, cerebrovascular, or peripheral vascular disease; inoperable coronary artery disease; and amputation for ischemic gangrene. RESULTS: On average VADT participants had high cardiovascular risk at entry into the study: 65.3% of the patients recruited were obese, 38.5% had previously had a vascular event, 78.7% had hypertension and 59.5% were using statins. During follow-up, 17.2%, 5.0%, 5.9%, 2.4% and 6.6% of participants had a primary composite endpoint, myocardial infarction, chronic heart failure, cardiovascular death or all-cause death, respectively. After adjusting for age, minority status, treatment arm and history of prior event, individuals in the lowest quartile of vitamin D (i.e., 1 to 15.9 ng/ml) were at similar risk of the primary composite endpoint [HR=1.26 (95% CI: 0.81, 1.96)], myocardial infarction [HR=1.13 (95% CI: 0.53, 2.42)], congestive heart failure [HR=1.44 (95% CI: 0.67, 3.06)], cardiovascular death [HR=0.86 (95% CI: 0.28, 2.63)], and death from any cause [HR=1.04 (95% CI: 0.53, 2.04)] as individuals in the highest quartile of vitamin D (i.e., 29.9 to 77.2 ng/ml). CONCLUSIONS: These data indicate that vitamin D status had no significant impact on the incidence of macrovascular events in a cohort of high-risk veterans with type 2 diabetes mellitus in which traditional risk factors were managed according to current treatment guidelines. SUPPORT: This work was supported by American Heart Association Grant-in-Aid AHA0755466U and the Research Service of the Charleston SC VA Medical Center.

Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus

2020 ◽  
Author(s):  
Mei-Zhen Wu ◽  
Yan Chen ◽  
Yu-Juan Yu ◽  
Zhe Zhen ◽  
Ying-Xian Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Specific Pattern

Abstract Aims  Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. Methods and results  A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06–37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67–7.89; P = 0.19). Conclusion  LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

scholarly journals Comparative risk evaluation for cardiovascular events associated with dapagliflozin vs. empagliflozin in real-world type 2 diabetes patients: a multi-institutional cohort study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Shih-Chieh Shao ◽  
Kai-Cheng Chang ◽  
Ming-Jui Hung ◽  
Ning-I Yang ◽  
Yuk-Ying Chan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Diabetes Patients

Abstract Background To compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin. Methods We conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium–glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients’ age, sex, laboratory data, co-morbidities, and concomitant medications. Results We identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73–1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14–2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49–1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80–1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49–0.95). Conclusion The risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.

scholarly journals Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Chongguang Lin ◽  
Chunhua Zhou ◽  
Xiangyang Gao ◽  
Hailin Shao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Thyroid Carcinoma ◽  
Kidney Function ◽  
Cardiovascular Outcome Trials ◽  
Secondary Outcomes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs).Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy.Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo.Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

scholarly journals Prevalent and Incident Heart Failure in Cardiovascular Outcome Trials of Patients With Type 2 Diabetes

2018 ◽  
Vol 71 (12) ◽  
pp. 1379-1390 ◽  
Author(s):  
Stephen J. Greene ◽  
Muthiah Vaduganathan ◽  
Muhammad Shahzeb Khan ◽  
George L. Bakris ◽  
Matthew R. Weir ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Incident Heart Failure

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.

Heart failure and type 2 diabetes: From cardiovascular outcome trials, with hope

2019 ◽  
Vol 21 (5) ◽  
pp. 1081-1087 ◽  
Author(s):  
Dario Giugliano ◽  
Juris J. Meier ◽  
Katherine Esposito
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials

scholarly journals GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Dario Giugliano ◽  
Lorenzo Scappaticcio ◽  
Miriam Longo ◽  
Paola Caruso ◽  
Maria Ida Maiorino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Significant Heterogeneity ◽  
Cardiovascular Outcome Trials ◽  
Receptor Agonists ◽  
All Cause Mortality

Abstract Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P < 0.001). Conclusions GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

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