Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective

2008 ◽  
Vol 42 (10) ◽  
pp. 1466-1474 ◽  
Author(s):  
Ujjaini Khanderia ◽  
Rodica Pop-Busui ◽  
Kim A Eagle
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Case Reports ◽  
Safety Data ◽  
Composite Endpoint ◽  
Absolute Magnitude ◽  
Data Sources ◽  
Increased Risk

Objective: To examine the cardiovascular effects of thiazolidinediones (TZDs), discuss concerns regarding this drug class and its relation to heart failure (HF) and myocardial infarction (Ml), and address the clinical implications of HF and Ml. Data Sources: Literature was accessed through MEDLINE (1979-April 2008) using the search terms type 2 diabetes mellitus. thiazolidinediones. cardiovascular events, heart failure, myocardial infarction, and edema. Reviews, meta-analyses, clinical trials, observational studies (case-control, cohort), and descriptive studies (case reports, caso series) were included. Study Selection and Data Extraction: All articles that were written in English and identified from the data sources were reviewed. Data Synthesis: The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes, with the subsequent addition of a TZD, sulfonylurea, or insulin if the target is not met. Beyond glucose lowering, TZDs improvo various factors associated with cardiovascular risk. Whether the effects translate into beneficial cardiovascular outcomes is controversial. In PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events), pioglitazone did not produce a significant reduction in the primary endpoint that included a composite of coronary and vascular deaths, but the secondary composite endpoint of all-cause mortality, Ml, or stroke was significantly reduced. Concerns related to HF have led to warnings in the labeling of TZDs. The drugs are contraindicated in patients with New York Head Association Class Ill or IV HF. Rosiglilazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small. Conclusions: Although the glycemic efficacy of TZDs is comparable to that of metformin, ad verso effects and higher costs make TZDs less appealing for initial therapy. Among the TZDs. pioglitazone should be considered based on cardiovascular safety data. In combination with metformin, pioglitazone may be particularly beneficial for patients wilh diabetes and metabolic syndrome. For patients on rosigfitazone who are achieving glycemic goals and tolerating the therapy without apparent complications, rosiglitazone may be continued.

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.

scholarly journals Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel I. Bromage ◽  
Tom R. Godec ◽  
Mar Pujades-Rodriguez ◽  
Arturo Gonzalez-Izquierdo ◽  
S. Denaxas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Acute Myocardial Infarction ◽  
Composite Endpoint ◽  
Care Hospital ◽  
Primary Care Hospital ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Secondary Endpoints

Abstract Background The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. Methods This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. Results 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1–1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01–1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62–0.93], P = 0.009). Conclusions Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.

P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pellicori ◽  
A Pernille Ofstad ◽  
D Fitchett ◽  
C Zeller ◽  
C Wanner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Adverse Events ◽  
Repeated Measures ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Safety Data ◽  
Increased Risk ◽  
Outcome Trial

Abstract Background The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years. Purpose To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline. Methods We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model. Results A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA. Conclusions In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.

New-onset type 2 diabetes in heart failure: impact of heart failure and death versus ischemic events – a Danish nationwide cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Zareini ◽  
P.B Blanche ◽  
A.H Holt ◽  
M.M Malik ◽  
D.P Rajan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Risk Ratio ◽  
Real Life ◽  
Ischemic Event ◽  
Increased Risk ◽  
The Absolute ◽  
Ischemic Events ◽  
New Onset

Abstract Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None

Galectin-3 predicts cardiovascular events in patients with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Funding Source ◽  
Increased Risk ◽  
Galectin 3 ◽  
Secondary Outcomes

Abstract Introduction Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels. Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age. Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III

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 &lt; 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 Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

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