Targeting Heart Failure in Diabetes
Heart failure patients are much more likely to have diabetes than the general population.
The incidence of heart failure (HF) is increasing as the world’s population ages and the rates of other, often comorbid, diseases (eg, diabetes, heart disease, obesity) increase.
HF patients are much more likely to have diabetes than the general population, and patients with diabetes are 2.5 times more likely to develop HF and have poorer clinical outcomes than patients without diabetes. Community-based studies even indicate that 30% to 40% of these patients will die within 1 year of diagnosis.
Now, an article published ahead-of-print in Current Diabetes Reports identifies an optimal glycated hemoglobin (A1C) level and recommends therapies for patients with comorbid diabetes and HF.
HF hospitalization and mortality follows a U-shaped curve from low to high A1C values. A summary of 3 trials found mortality is lowest for patients with A1C values between 7.5% and 8%.
Hyperglycemia contributes to chronic HF and worsens acute HF, and certain treatments affect HF’s development and progression. Less than 5% of patients with an A1C value of 7% develop HF, but 72% of patients with an A1C exceeding 10% develop HF.
Large trials investigating the effect of intensive glycemic control on HF outcomes were inconclusive due to low rates of HF in enrolled cohorts. The investigators designed the trials to measure death, non-fatal myocardial infarction, and nonfatal stroke. However, observational studies with sicker patients have found a strong relationship between hyperglycemia and HF-related hospitalizations and mortality.
The ASTRONAUT (aliskiren) and EVEREST (tolvaptan) trials found participants with diabetes had higher hospitalization and mortality shortly after discharge for HF. Both trials found patients with diabetes were approximately 20% more likely to have an adverse outcome than the cohort as a whole.
A retrospective analysis of patients with HF and diabetes treated in Veterans Affairs medical centers found metformin users were less likely to die of HF than nonmetformin users. A number of confounding variables exist, including the severity of the patients’ HF and comorbid conditions (especially renal failure). Providers should not avoid using metformin in patients with diabetes and HF unless they are at risk for acute decompensated HF or lactic acidosis.
This review discusses specific drugs:
· An observational study found insulin-dependent diabetics experience staggering HF-related mortality. Only 62.1% of insulin users survived a year after enrollment, but 85.8% of non—insulin-dependent diabetics were still alive. The most significant influence is diabetes severity; insulin-dependent type 2 diabetics tend to have more serious diabetes and a greater risk of severe hyperglycemia without insulin.
· The thiazolidinediones pioglitazone and rosiglitazone cause fluid retention and edema through their effect on the kidneys. These medications worsen HF and may increase the risk of HF development.
· The dipeptidyl peptidase-4 inhibitors may increase the risk of HF as a class, but sitagliptin may have no effect. Variable study designs prevent close and clear comparison, and the class may have no impact in HF after all. Sitagliptin is the preferred class member in patients with comorbid HF at this time.
· The LEADER trial found liraglutide reduced cardiovascular mortality without any negative impact on HF. This may be specific to liraglutide or a class effect, and future study should clarify this relationship.
· The EMPA-REG CV outcome trial found empagliflozin decreases HF-related hospitalization and mortality in high-risk patients. The sodium/glucose cotransporter-2 inhibitors promote weight loss, lower blood pressure, correct hyperglycemia, and create a ketogenic environment. Research is ongoing to determine if the entire class reduces HF outcomes.
Up to half of HF patients have diabetes. Knowledge about the relationships between antihyperglycemic medications and HF is growing rapidly. Providers need new strategies and an increased understanding of comorbid diabetes and HF.