Impact of Oral Antidiabetics on Heart Failure
Diabetes mellitus is primarily perceived as a risk factor for ischemic heart disease and general atherosclerotic complications. However, an equally significant problem is the association between diabetes and heart failure. This hypothesis is confirmed by the VALUE study, which primarily focused on arterial hypertension. Its results show that individuals with diabetes had a higher risk of heart failure compared to the risk of acute myocardial infarction.
Heart Failure in Diabetics
The etiology of heart failure in diabetics is multifactorial with various clinical manifestations. Heart failure may arise from coronary macro- and microangiopathy, metabolic damage to the myocardium, diabetic neuropathy, and several other causes. Diabetics constitute approximately one-third of all patients with heart failure. This typically includes patients with reduced heart fraction and decreased cardiac output, but many diabetics are diagnosed with heart failure with preserved ejection fraction. The prognosis for diabetic patients diagnosed with heart failure is very poor. The mortality rate is 32.7% per year, compared to 3.7% per year in diabetics without heart failure.
Empagliflozin in the Treatment of Heart Failure
A large meta-analysis, whose results were presented by Professor Aleš Linhart from the 2nd Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, revealed that some antidiabetics might increase the risk of heart failure. Specifically, these included glitazones, saxagliptin, and alogliptin. Intensive regimens and insulin therapy presented a neutral risk in this meta-analysis. Weight reduction represented a risk with a trend towards decrease.
Significant breakthrough findings come from the international EMPA-REG OUTCOME study, which demonstrated that empagliflozin is the first antidiabetic that significantly reduces cardiovascular risk compared to placebo. Professor Linhart specifies that the divergence of Kaplan-Meier curves illustrating hospitalization for heart failure occurs within the first few months of treatment initiation (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.50–0.85; p = 0.002). The likely multifactorial cause of this phenomenon includes empagliflozin's contribution to weight reduction, blood pressure decrease, and inducing osmotic diuresis.
Post-hoc analysis of this study further confirms that the benefit of empagliflozin is practically identical in patients with and without a history of heart failure. Empagliflozin also significantly prolongs the time until initiation of loop diuretics treatment for heart failure NYHA class II–III (HR 0.62; 95% CI 0.53–0.73; p = 0.001). The time to hospitalization for heart failure or the start of loop diuretics therapy is also significantly prolonged with empagliflozin (HR 0.63; 95% CI 0.54–0.73; p = 0.001).
Conclusion
Diabetes mellitus represents a significant risk for the development of heart failure. The results of the EMPA-REG OUTCOME study indicate that treatment of diabetes with empagliflozin significantly reduces this risk.
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Source: Practical Guide to Treatment of Type 2 Diabetes. Seminar with panel discussion, organized by the 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague in collaboration with the 2nd Department of Internal Medicine, Faculty of Medicine, Masaryk University and St. Anne's University Hospital in Brno. April 18, 2016, Prague.
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