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New statement from the AHA / HFSA on Diabetes and Heart Failure

The American Heart Association (AHA) and the Heart Failure Society of America (HFSA) have released a new scientific report on the management of type 2 diabetes mellitus and heart failure.

The statement – that the document notes does not represent an update of the 2017 Heart Failure Directive from the American College of Cardiology / AHA / HFSA – sums up what we know from the Epidemiology and pathology of diabetes and its impact on heart failure outcomes, reviews the management of both conditions, and examines possibilities for future research, say the authors.

Dr. Shannon Dunlay

"The main purpose of this statement is to bring clinician practitioners up to date on this topic," said Shannon M. Dunlay, MD, co-chair of the group, associate professor of health services and medicine research, advanced cardiologist, Mayo Clinic. , Rochester, Minnesota, said theheart.org | Medscape Cardiology.

"We have known for some time that diabetes and heart failure are common, often occur together and often require medication to treat one or the other problem," she said. . However, although separate guidelines cover the management of diabetes and heart failure, guidelines for the care of patients with both conditions are inadequate.

The statement was published online on June 6 in circulationand in the Journal of Heart Failure.

The authors note that the number of patients diagnosed with MS and HF is increasing. About 30.3 million Americans, or 9.4% of the US population, have DM and 6.5 million HA, and an estimated 1.5 to 2 million people are suffering from two conditions, said Dunlay.

Diabetes is a "powerful" risk factor for heart failure and some data suggest that heart failure increases the risk of developing diabetes, Dunlay said. "The metabolic derangements associated with diabetes can be toxic to the heart and cause heart failure.Also, both conditions are characterized by inflammation, which can increase the risk of development of the other."

Drugs used to treat one condition may also affect the results of the other, Dunlay said. "In recent years, for example, data have shown us that the drugs we use to treat hyperglycemia in diabetics may have an impact on the risk of developing heart failure or results. mediocre, including hospitalization for heart failure, in patients with diabetes, cardiac arrest. "

Glycemic control

Intensive treatment aimed at achieving low HbA1c targets in type 2 diabetes reduces the long-term risk of microvascular events such as retinopathy, nephropathy and peripheral neuropathy. Although intensive glycemic control does not appear to reduce the risk of all-cause mortality, cardiovascular mortality or stroke, it can reduce the risk of nonfatal myocardial infarction, said authors.

Optimal glycemic targets for patients with diabetes mellitus and HF should be individualized to reflect the burden of comorbidity, including the severity of HF, and to balance the benefits likely to be achieved by lowering HbA1c with potential risks. The authors noted that hypoglycemia, polypharmacy, treatment load and high cost of care were the potential disadvantages of intensive treatment.

The benefits of hypoglycemic treatment should be considered in the broader context of the patient's life expectancy because, as the authors point out, there is a delay of nearly 10 years before one can benefit from more intensive glycemic control.

Given the lack of specific HF data to guide HbA1c goals in patients with diabetes and IC, the authors suggest a target range of HbA1c of 7% to 8% for most patients with HF, according to clinical practice recommendations for DM.

Therapeutic decisions should also consider the potential benefits and harms of each hypoglycemic drug. The authors reviewed these drugs, including:

metformin: Metformin, a biguanide, is the preferred initial pharmacotherapy in patients with type 2 diabetes in the absence of contraindications. Metformin is effective, safe and generally well tolerated, they write.

Although metformin was previously contraindicated in heart failure because of concerns about the rare risk of lactic acidosis, many observational studies suggest a benefit in terms of survival, said the authors.

The authors concluded that it was reasonable to use metformin in patients with diabetes at risk for HF or established HF. Metformin should be discontinued in patients with acute conditions associated with lactic acidosis, such as cardiogenic or distributive shock.

Sulphonylurea Drugs: There is little data on the use of sulfonylurea and the development of heart failure in patients with diabetes. Other agents, such as metformin and SGLT-2 inhibitors, are preferable in patients at high risk of heart failure and in those with established heart failure, note.

The ongoing CAROLINA study (a study of the cardiovascular effects of linagliptin versus glimepiride in patients with type 2 diabetes) will provide up-to-date data on the cardiovascular safety of sulfonylurea drugs, including the effects of hospitalization for IC, they noted. (The results of CAROLINA have just been presented at the meeting of the American Diabetes Association and are reported by Medscape Medical News; The report can be found here.)

Insulin: The only randomized controlled trial to specifically evaluate the cardiovascular safety of insulin was the ORIGIN trial (Reduced Outcomes with Initial Glargine Intervention). As part of this study, 12,537 patients with pre-DM or diabetes were randomized to receive insulin glargine or standard care, and no cardiovascular difference, including hospitalization for an insufficiency cardiac, has been highlighted.

However, observational studies have suggested an increase in IC with insulin therapy. Most observational studies and subgroup analyzes of clinical trials, but not all, have shown that insulin use is associated with a higher risk of death in patients with DM and FH .

The authors noted that the use of insulin was associated with weight gain and risk of hypoglycemia and should be used with caution and under close supervision. Other agents, such as metformin and SGLT-2 inhibitors, are preferred if adequate glycemic control can be achieved without insulin, they say.

Thiazolidinedione drugs: Randomized controlled trials have shown that thiazolidinedione (TZD) -based drugs are associated with an increased hospitalization rate for heart failure in patients without starting heart failure. The association of TZD with an increased risk of HF has also been demonstrated in patients with diabetes mellitus and heart failure with reduced ejection fraction (HFrEF),

TZDs are not recommended in patients with established HF and may increase the risk of HF events in people with DM without HF, said the authors.

GLP-1 receptor agonists: GLP-1 (Glucagon-like peptide-1) receptor agonists stimulate the release of glucose-dependent insulin with a low risk of hypoglycemia. Significant side effects include decreased appetite and dietary intake (resulting in weight loss) and improved lipid levels, decreased triglyceride levels, and increased high density lipoproteins.

GLP-1 receptor agonists may reduce the risk of major adverse cardiovascular events and mortality in MS patients. In large-scale clinical trials, they did not have an impact on the risk of hospitalization for heart failure, suggesting that they are safe but not beneficial for preventing heart failure. in patients at risk for HF, they write.

In patients with established HFrEF and recent decompensation, GLP-1 receptor agonists should be used with caution, in the absence of evidence of benefits and a tendency to degradation of the results. in two small randomized controlled trials, the authors said.

Inhibitors of Dipeptidyl Peptidase-4: Dipeptidyl peptidase-4 (DPP-4) is an enzyme involved in the rapid degradation of GLP-1. Therefore, the effects of the incretin system could be enhanced by the inhibition of DPP-4. Alogliptin, linagliptin, saxagliptin and sitagliptin are FDA approved oral therapies for the treatment of type 2 diabetes.

There is no indication that DPP-4 inhibitors have cardiovascular benefits. In patients with diabetes at high cardiovascular risk, some DPP-4 inhibitors may increase the risk of hospitalization for IC, the authors said.

The effects in patients with established heart failure have not been well studied, as some potentially disturbing signals have been reported during mechanistic trials.

"Based on these data, the benefit-risk ratio for most DPP-4 inhibitors does not warrant their use in patients with established heart failure or those at high risk of heart failure," write the authors.

SGLT-2 inhibitors: Inhibitors of SGLT-2 lower glucose by increasing urinary excretion. In addition, they increase the fractional excretion of sodium and have modest diuretic and natriuretic effects. Canagliflozin, dapagliflozin and empagliflozin are approved by the FDA for the treatment of type 2 diabetes.

"SGLT-2 inhibitors may be a good choice for diabetic patients at high risk of heart failure or already suffering from heart failure because they can reduce the risk of cardiovascular events and complications. 39 hospitalization for heart failure, "said Dunlay.

"Recent studies have consistently demonstrated that trials are underway to determine if SGLT-2 inhibitors are useful in the treatment of heart failure, even in non-diabetic patients," he said. -she adds.

Dunlay said she was "very excited" to learn more about the functioning of SGLT-2 inhibitors and how best to use them for heart failure management, at the same time. times in reduced EF and preserved.

The authors cautioned, however, that the cardiovascular benefits of SGLT-2 inhibitors should be weighed against their potential risks, including genital candidiasis and other rare complications such as eukemicemic diabetic ketoacidosis. amputation of the lower limbs and fractures.

The authors also summarized existing data comparing the efficacy of HF treatments in patients with and without diabetes. These included:

ACE Inhibitors: A meta-analysis of 6 trials of angiotensin-converting enzyme (ACE) inhibitors showed a reduction in morbidity and mortality in patients with heart failure with or without diabetes. The pooled analysis of 2398 patients revealed a relative risk of death of 0.84 (95% confidence interval). [CI]0.70 – 1.00) in patients with diabetes vs. 0.85 (95% CI, 0.78-0.92) in those without DM.

Similar results were observed in pivotal HF trials on angiotensin receptor antagonists (ARBs). The research also uncovered therapeutic benefits of sacubitril-valsartan, neprilysin inhibitor (ARNI), an angiotensin receptor, in patients with and without diabetes, the authors noted.

Mineralocorticoid receptor (MRA) antagonists have been shown to have consistent benefits in HFrEF patients with and without DM.

β-blockers: Most of the meta-analyzes of β-blockers by DM status have demonstrated a consistent benefit in people with MS and HFrEF, although one has suggested a comparatively higher benefit in people without DM, noted the authors.

Overall, the three FDA-indicated β-blockers for use in HFrEF (carvedilol, metoprolol succinate, and bisoprolol) have been shown to significantly reduce morbidity and mortality in people with DS.

ivabradine: As part of the SHIFT trial (ivabradine versus placebo) as part of the SHIFT trial, ivabradine significantly reduced the primary endpoint of cardiovascular death assessment. or hospitalization related to heart failure in patients with or without DM (interaction P = 0.57). There was also a significant reduction in hospitalization for HF in both groups.

Implantable therapy: In general, pivotal trials involving both implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) have shown consistent benefits in patients with or without MD.

Some of the most recent data show that left ventricular assist device (LVAD) treatment can improve glycemic control in diabetic patients, Dunlay said. "This is important because LVAD essentially improves heart failure, which can improve diabetes control."

Patients with chronic renal failure

The authors concluded that metformin was a reasonable first-line treatment in patients with chronic renal failure and chronic renal failure (CKD), provided that the estimated glomerular filtration rate is greater than 30 ml / min / 1.73 m2.

Insulin is safe for patients with chronic kidney disease and heart failure, although lower doses are needed in case of kidney failure. Clinicians may consider other hypoglycaemic agents, although dosage adjustment may be required in patients with chronic kidney disease, and the risk of adverse events may be increased when renal function decreases, the authors said. .

The use of SGLT-2 inhibitors in patients with chronic kidney disease seems promising given their benefits in terms of heart failure and their potential for renal protection. However, the authors pointed out that the results of ongoing clinical trials were necessary to ensure their safe use at lower levels of GFR.

The authors emphasized the need for collaborative management of DM and HF. "It's easy to focus on the main disease you are dealing with, such as heart failure, but it's important to think about how other diseases of the patient, including diabetes, may be affected by the drugs you use, "said Dunlay.

She emphasized that team-based care is essential. "Communication and care coordination are so important for patients with complex treatment regimens and complex medical conditions such as diabetes and heart failure."

Lifestyle management is another important part of managing these patients, said Dunlay. "Exercise is safe and beneficial for patients with heart failure and diabetes."

The American Heart Association and the Heart Failure Society of America strive to avoid any real or potential conflict of interest that may arise from an outside relationship or from personal, professional, or business interests. of a member of the drafting group.

circulation. Posted online June 6, 2019. Summary

Journal of Heart Failure. Posted online June 6, 2019. Summary

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