Association Between Type 2 Diabetes and All-Cause Hospitalization and Mortality in the UK General Heart Failure Population

Aims Impact of type 2 diabetes mellitus (T2DM) on non‐thromboembolic outcomes in atrial fibrillation (AF) is insufficiently explored. This prospective cohort study of AF patients aimed (i) to analyse the association between T2DM and heart failure (HF) events (including new‐onset HF), and all‐cause and cardiovascular mortality, (ii) to assess the impact of baseline T2DM treatment on outcomes, and (iii) to explore characteristics of new‐onset HF phenotypes in relation to T2DM status. Methods and results Of 1803 AF patients (515/1288, with/without prior HF), 389 (22%) had T2DM at baseline. After 5 years of median follow‐up, T2DM patients had an 85% greater risk of HF events [adjusted hazard ratio (aHR) 1.85; 95% confidence interval (CI) 1.51–2.28; P < 0.001], including a 45% increased risk for new‐onset HF (1.45; 1.17–2.28; P = 0.015). T2DM conferred a 56% higher all‐cause (1.56, 1.22–2.01; P = 0.003) and a 48% higher cardiovascular mortality (1.48; 1.34–1.93; P = 0.007). Fine–Gray analysis, with mortality as a competing risk, confirmed greater HF risk among T2DM patients. All risks were highest among insulin‐treated patients. The prevalence of new‐onset HF phenotypes was as follows: 67% preserved ejection fraction (HFpEF), 20% mid‐range ejection fraction (HFmrEF) and 13% reduced ejection fraction (HFrEF). On time‐dependent Cox regression, adjusted for baseline characteristics and an interim acute coronary event, T2DM increased aHRs for new‐onset HFpEF (2.38; 1.30–4.58; P <0.001) and the combined HFmrEF/HFrEF (1.77; 1.11–3.62; P = 0.017). Conclusions Atrial fibrillation patients with T2DM have independently increased risk of new‐onset/recurrent HF events, cardiovascular and all‐cause mortality, particularly when insulin‐treated. The prevailing phenotype of new‐onset HF was HFpEF; T2DM conferred higher risk of both HFpEF and HFmrEF/HFrEF.

Section: Discussionmentioning

confidence: 94%

Section: The Association Between Type 2 Diabetes Treatment and Outcomesmentioning

confidence: 98%

Type 2 diabetes increases the long‐term risk of heart failure and mortality in patients with atrial fibrillation

Polovina

Lund

Đikić³

et al. 2019

“…150 Insulin-related hypoglycaemia may also activate the sympathetic nervous system and promote arrhythmogenesis. 151 Accordingly, insulin use has been accompanied by an increased risk for AF 152,153 and HF 154,155 and an enhanced likelihood of poor outcomes (including stroke) in patients with established HFpEF. 73,156,157…”

Section: Effects Of Antihyperglycaemic Drugs In Patients With a Metabmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

“…Most data suggest that mortality risk in patients with HF is lowest with moderate glycaemic control (i.e. HbA 1c levels 7.0–7.9%) . Therefore, the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of HF stipulate that adequate glycaemic control should be achieved gradually and leniently, with agents shown to be safe and effective .…”

Section: Introductionmentioning

confidence: 99%

“…HbA 1c levels 7.0-7.9%). [10][11][12][13][14] Therefore, the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of HF stipulate that adequate glycaemic control should be achieved gradually and leniently, with agents shown to be safe and effective. 15 A holistic approach to T2DM management in HF should also include blood pressure, body weight, and lipid control, while avoiding hypoglycaemia, which is associated with a greater risk of death 16 and may be a cause of increased mortality in diabetic patients with HF on insulin therapy.…”

Section: Introductionmentioning

confidence: 99%

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Seferović

Coats

Ponikowski

et al. 2019

147

122

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose‐lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA), and sodium–glucose co‐transporter type 2 (SGLT‐2) inhibitors]. Regarding safety of DPP‐4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP‐4 inhibitors. GLP‐1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT‐2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT‐2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT‐2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose‐lowering therapies in patients with HF.