Dapagliflozin — a key pawn on the new guidelines chessboard

Abstract

Treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) aims to reduce mortality, prevent rehospitalizations due to heart failure (HF) exacerbation, and improve the clinical status, functional capacity, and quality of life. All these goals were achieved in the DAPA-HF trial. In this trial, the reduction in the primary outcome, defined as a composite of worsening of HF or cardiovascular death, was achieved in patients receiving dapagliflozin [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65-0.85; p < 0.001) as compared with placebo. In addition, the beneficial effect of dapagliflozin on the primary outcome was generally consistent across prespecified subgroups regardless of baseline treatment, diagnosis of diabetes, or left ventricular ejection fraction (LVEF).Data from multiple countries was obtained in the CVD-REAL study. The use of different sodium-glucose co-transporter 2 (SGLT2) inhibitors, versus other glucose-lowering drugs, was associated with lower rates of hospitalization for HF (HR 0.61; 95% CI 0.51-0.73; p < 0.001) and death (HR 0.49; 95% CI 0.41-0.57; p < 0.001). These findings were confirmed in the CVD-REAL-2 study.The exceptional clinical benefits of SGLT2 inhibitors applied on top of the previously guideline-recommended treatment in patients with chronic HFrEF led to fundamental changes in the recommended treatment strategy proposed in the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic HF.To conclude, the new treatment algorithm for HFrEF is based on the findings of many groundbreaking trials. However, it is the results of trials with SGLT2 inhibitors, applied in patients with HFrEF on top of the optimal treatment including an implantable cardioverter-defibrillator and/or cardiac resynchronization therapy, that have fundamentally changed the strategy of treatment.

Functioning in chronic disease — a key factor determining adherence to heart failure treatment

“…Both of these studies consistently showed that the incidence of side effects and the rate of therapy discontinuation were lower in patients receiving SGLT2i compared to placebo, although the differences were not statistically significant [33,34]. Moreover, treatment with dapagliflozin as well as with empagliflozin was associated with improvement in HF-related symptoms, function, and quality of life [33][34][35][36][37][38].…”

Efficacy of double vs. standard empagliflozin dose for METabolic syndromE tReatment (DEMETER — SIRIO 11) study. Rationale and protocol of the study

“…The SGLT2 inhibitors have also been shown to reduce serum uric acid levels in a dose-dependent manner [14] and reduce urinary albumin excretion in patients with type 2 diabetes and prevalent micro-or macroalbuminuria [15]. Furthermore, the anti-inflammatory effect of SGLT2 inhibitors with a slight reduction in serum inflammatory markers: hsCRP, tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and interferon-gamma (IFN-g) has been revealed [16] explaining the beneficial effect of SGLT2 inhibitors at the kidney and myocardium levels [2,17,18].…”

Treatment of heart failure patients — in search of new solutions to difficult problems

“…To achieve these goals a new simplified treatment algorithm has been introduced [1]. The cornerstone of management is therapy with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-I), unless the drugs are contraindicated or not tolerated (class I of recommendations) [1][2][3][4]. Moreover, importance of multidisciplinary team management, education, self-care, lifestyle advice, exercise training, follow-up, and monitoring to improve therapeutic effectiveness has been highlighted [1,3].…”