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

Greene, Stephen J.; Vaduganathan, Muthiah; Khan, Muhammad Shahzeb; Bakris, George L.; Weir, Matthew R.; Seltzer, Jonathan; Sattar, Naveed; McGuire, Darren K.; Januzzi, James L.; Stockbridge, Norman; Butler, Javed

doi:10.1016/j.jacc.2018.01.047

Cited by 52 publications

(35 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite this robust evidence, HF seems to have been neglected by clinicians and scientists who dedicate more attention to the atherothrombotic complications of diabetes. HF remains one of the most common and serious complications of diabetes and is, in fact, as common as the occurrence of ischemic events, with perhaps even higher rates . HF in the context of diabetes mellitus is attributed to macrovascular and microvascular dysfunction, volume overload, impaired renal function and the direct effects of diabetes mellitus and insulin resistance on cardiac myocytes .…”

Section: Hf Risk Has Not Changed Despite Improvement In CV Outlookmentioning

confidence: 99%

“…HF remains one of the most common and serious complications of diabetes and is, in fact, as common as the occurrence of ischemic events, with perhaps even higher rates. 17 HF in the context of diabetes mellitus is attributed to macrovascular and microvascular dysfunction, volume overload, impaired renal function and the direct effects of diabetes mellitus and insulin resistance on cardiac myocytes. 18 Unfortunately, more traditional glucose-lowering agents have not proven to be effective in reducing HF risk in patients with T2D.…”

Section: Advance (Action In Diabetes and Vascular Disease: Preterax Andmentioning

confidence: 99%

See 1 more Smart Citation

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

Giugliano

Meier

Esposito

2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

An excess risk of heart failure (HF) persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been published to date, although none, with the exception of the DECLARE trial with dapagliflozin, has included HF as a primary endpoint. The four trials with dipeptidyl‐peptidase inhibitors (DPP‐4i) (SAVOR‐TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin which was associated with a 27% increased risk. Five completed CVOTs with the GLP‐1 RAs lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN‐6), exenatide once weekly (EXSCEL) and albiglutide (HARMONY) also failed to reveal any significant effect on HF risk. The three trials with sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) (EMPA‐REG OUTCOME with empagliflozin, CANVAS with canagliflozin and DECLARE with dapagliflozin) all revealed a robust and significant reduction in the hazard ratios of hospitalization for HF, from 27% to 35%, which remained consistent, significant and of similar magnitude regardless of the presence of a history of HF or established atherosclerotic cardiovascular disease. There is no association between reductions in HF risk and haemoglobin A1c (A1C) levels, while there is a significant association between reductions in HR for MACE and A1C levels (Spearman's correlation, r = 0.695; P = 0.013). All of the 12 CVOTs completed to date have provided reassurance of the overall cardiovascular safety of the newer anti‐hyperglycaemic drugs. At present, the robust, consistent and reproducible reduction of approximately 30% in the risk of HF with SGLT‐2i may be considered a class effect. The beneficial effect on MACE outcome observed with the use of some GLP‐1RAs and SGLT‐2i must be interpreted within the frame of the single trial.

show abstract

Section: Hf Risk Has Not Changed Despite Improvement In CV Outlookmentioning

confidence: 99%

Section: Advance (Action In Diabetes and Vascular Disease: Preterax Andmentioning

confidence: 99%

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

Giugliano

Meier

Esposito

2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…Despite the tremendous advancement of science and the establishment of new therapeutic targets in type 2 diabetes mellitus care, the capture of heart failure−specific information in completed CVOTs has been limited. 5 In a recent systematic review 5 of large CVOTs of major therapeutic programs in type 2 diabetes mellitus, heart failure at baseline and during follow-up was infrequently defined. When provided, only a subset of patients enrolled carried a baseline history of heart failure, ranging from 1% to 28% across trials.…”

Section: Caveats Of Completed Cvotsmentioning

confidence: 99%

“…4 In the last decade, more than 20 largescale CVOTs enrolling more than 150,000 randomized patients have been conducted (Figure 1). 5 Nearly all these clinical trial programs have studied a primary endpoint of major adverse cardiovascular events (MACE), namely nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; heart failure has infrequently been included as a primary or secondary clinical endpoint in CVOTs. 5 In this review, we discuss the central importance of heart failure as a therapeutic endpoint in type 2 diabetes mellitus care, particularly in the context of the sodium-glucose co-transporter 2 (SGLT2) inhibitor class of glucose-lowering therapies.…”

Section: Introductionmentioning

confidence: 99%

Preventing and Treating Heart Failure with Sodium-Glucose Co-Transporter 2 Inhibitors

Vaduganathan

Januzzi

2019

The American Journal of Medicine

Self Cite

View full text Add to dashboard Cite

Heart failure is a common complication among patients with type 2 diabetes mellitus and is associated with significantly increased risks of subsequent morbidity and mortality. Until recently, therapies and strategies were lacking to attenuate this excess risk of heart failure in this population. Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a unique class of glucose-lowering therapies that have multisystem health benefits. Three large cardiovascular outcomes trials have demonstrated consistent reductions in heart failure events among patients with type 2 diabetes mellitus with, or at risk for, atherosclerotic cardiovascular disease. Another trial recently showed that an SGLT2 inhibitor, canagliflozin, also significantly reduced heart failure events among patients with type 2 diabetes mellitus and albuminuric chronic kidney disease. The SGLT2 inhibitor class represents an important new therapeutic approach for the prevention of heart failure in at-risk patients with type 2 diabetes mellitus, and is actively being studied for use in treating patients with heart failure (with or without type 2 diabetes mellitus).

show abstract

“…According to over 40 clinical trials conducted from 1999 to 2007, rosiglitazone has been reported to increase risks of heart failure [13,14] and myocardial infarction in T2DM patients [15][16][17]. Additionally, rosiglitazone was associated with a significant increase in the risk of death from cardiovascular causes that had borderline significance [13,16,18,19]. Rosiglitazone may also worsen the clinical course in patients with pre-existing left ventricular dysfunction [20].…”

Section: Introductionmentioning

confidence: 99%

Thiazolidinediones Cause Cardiotoxicity via PPARγ- Independent Mechanism

Jiang¹,

Balschi²,

McGowan³

et al. 2018

Cardiotoxicity

View full text Add to dashboard Cite

Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are highly effective antidiabetic drugs that are widely used to treat type 2 diabetes mellitus (T2DM) due to their unique beneficial actions, such as a renoprotective effect, amelioration of glucose homeostasis, and blood pressure lowering, that other antidiabetic drugs do not have. Those beneficial actions, however, are shadowed by the increased risks of cardiovascular adverse events, including mitochondrial dysfunction, oxidative stress and myocardial energy deficiency, fluid retention, congestive heart failure, and myocardial infarction. Except PPARγ, TZDs also have affinity to numerous non-PPARγ targets in mitochondria, cytosol, and cytoplasm, including MitoNEET, mitochondrial pyruvate carrier, dehydrogenases involved in tricarboxylic acid cycle and electron transport, cytoplasmic ion channels, Na-K-pump, and other unknown enzymes. By binding to these targets, TZDs produce off-target effects and potentially increase cardiotoxicity. In this chapter, we review recent studies, both experimental and clinical, on the myocardial adverse effects associated with TZDs and their underlying mechanisms. We focus our review in large part on the relationship between these myocardial adverse effects and PPARγ.

show abstract

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

Cited by 52 publications

References 69 publications

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

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

Preventing and Treating Heart Failure with Sodium-Glucose Co-Transporter 2 Inhibitors

Thiazolidinediones Cause Cardiotoxicity via PPARγ- Independent Mechanism

Contact Info

Product

Resources

About