• Clinical Challenges: Heart Failure Protection in Diabetes Drugs

    What is the link between HF, diabetes?

    Heart failure is highly prevalent in patients with diabetes and worsens their prognosis, although there may be some good news: researchers are finding that some diabetes drugs may offer heart protection that extends beyond glycemic control alone.

    Diabetes itself is an independent risk factor for onset of heart failure, with a population attributable risk of 6%-12%, which is the estimate of the proportion of heart failure cases that would not occur if diabetes were removed from the picture, according to James Januzzi, MD, of Massachusetts General Hospital in Boston.

    Studies place the incidence of diabetes at 12%-30% of the heart failure population, the odds rising with age, according to a review in European Heart Journal. Additionally, a separate Diabetes Care study of almost 10,000 patients with type 2 diabetes found that 11.8% had heart failure upon entering the study; another 7.7% developed heart failure during the next 30 months.

    "Furthermore, once a patient with diabetes develops heart failure, their prognosis is dramatically worsened. Those with diabetes mellitus and HFpEF [heart failure with preserved ejection fraction] have the same mortality risk as those without diabetes mellitus suffering from HFrEF [heart failure with reduced ejection fraction], a generally higher-risk patient population," Januzzi told MedPage Today.

    Thus, the American College of Cardiology (ACC) and the American Diabetes Association are working in tandem to optimize the care of patients with diabetes and cardiovascular disease including heart failure. "On the ACC side, we have an Expert Consensus Decision Pathway specifically focused on optimizing cardiovascular care in those with diabetes mellitus, with focus on reducing risk for heart failure," said Januzzi, who is the chair of the task force in charge.

    Evidence of subclinical heart damage can be found in the form of a high-sensitivity cardiac troponin test among hyperglycemic patients with no known coronary artery disease or heart failure. For those with diabetes, the enzyme levels were especially high, according to a population study.

    Women with diabetes appear to have six times the risk of developing heart failure -- compared with two times higher for men in the Framingham Heart Study. Why the female sex should be more likely than male counterparts to develop this condition remains unclear, with no strong mechanisms connecting diabetes and heart failure.

    "Until the past decade, there was a generally poor understanding regarding how diabetes mellitus medications affected risk for incident heart failure, or how it modified the course of prevalent heart failure," Januzzi said, noting a general consensus that older medications such as insulin and metformin were safe.

    It wasn't until the thiazolidinediones were associated with cardiovascular risk that the FDA mandated that researchers look more closely at the safety of diabetes drugs in cardiovascular outcomes trials. Since then, other drugs for glucose control were associated with a similar risk, including DPP-4 inhibitors. However, these were arguably cleared for cardiovascular safety upon further study.

    On the other hand, some diabetes drugs may actually offer protection from heart failure.

    The EMPA-REG trial, published in the New England Journal of Medicine, was the first to show an improvement in cardiovascular mortality with a diabetes drug, an SGLT-2 inhibitor. In the study, the drug made no difference in the vascular events of myocardial infarction and stroke, but drove down rates of heart failure, cardiovascular mortality, and overall mortality over 3 years.

    The heart failure benefit remained robust regardless of the dose or the patient's baseline hemoglobin A1C level, leading experts to speculate that the SGLT-2 inhibitor works through more than glycemic control.

     

    Two ongoing trials on this drug are EMPEROR-Reduced and EMPEROR-Preserved, which investigate the use on top of guideline-directed medical therapy in HFrEF and HFpEF, respectively. For now, signals of increased risk of ketoacidosis and amputation remain concerns regarding the SGLT-2 inhibitor class of medication.

    Also thought to have potential for the prevention or treatment of heart failure are the JAK inhibitors, known to work in inflammatory conditions.

    Yet inflammation is only one part of the puzzle, Januzzi said. "Though it is true that inflammation is more prevalent in those with diabetes mellitus, mechanisms of heart failure in patients with the diagnosis of diabetes mellitus are far more complex, including higher risk for coronary artery disease and the development of so-called 'diabetic cardiomyopathy,' which is only in part linked to inflammation."

    Source:

    Read the original article on Medpage Today: Clinical Challenges: Heart Failure Protection in Diabetes Drugs

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