NEWS & PERSPECTIVE
Dapagliflozin reduces combined risk of HF worsening or CV death in patients with HFmEF or HFpEF
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, are strongly recommended by clinical guidelines for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF).1 Recently, emerging data have suggested that the benefits of SGLT2 inhibitors may extend to HF patients with mildly reduced or preserved ejection fraction (HFmEF or HFpEF).2 In the DELIVER trial, dapagliflozin has demonstrated a significant reduction in the risk of HF worsening and cardiovascular (CV) death in patients with HFmEF and HFpEF, supporting its use in HF patients, regardless of the left ventricular ejection fraction (LVEF).3
SGLT2 inhibitors were originally used for the management of type 2 diabetes mellitus.4 Due to their diuretic effect, the drugs can decrease blood and interstitial fluid volume, thus lowering the preload and afterload of the heart and achieving a lower left ventricular end-diastolic volume and pressure.5 With that, SGLT2 inhibitors are believed to be able to elicit a therapeutic effect in heart failure.5 Previously, a number of randomized trials have demonstrated the clinical benefits of SGLT2 inhibitors in HFrEF, providing additional treatment options for patients.3 Yet, for patients with HFmEF or HFpEF, pharmacological treatment choices remain limited.
The DELIVER trial is a phase 3, double-blinded, multicenter randomized controlled trial which included 6,263 patients aged ≥40 years, with a stable heart failure of a left ventricular ejection fraction of >40%, structural heart disease and increased level of natriuretic peptide.3 These patients were randomly assigned to either the dapagliflozin (n=3,131) or placebo (n=3,132) group.3 The primary outcome was a composite of worsening HF (defined as either an unplanned hospitalization for HF or an urgent visit for HF) or CV death.3 Secondary outcomes included frequency of worsening HF events, CV deaths, death from any cause, and change in total symptom score based on the Kansas City Cardiomyopathy Questionnaire (KCCQ) at month 8.3
The primary outcome occurred in 16.4% (n=512) in the dapagliflozin and 19.5% (n=610) in the placebo group, demonstrating a significantly reduced risk with dapagliflozin of 18% vs. placebo (HR=0.82; 95% CI: 0.73-0.92; p<0.001).3 The frequencies of worsening HF events were also lower in the dapagliflozin group (11.8%) as compared to that in the placebo (14.5%) group (HR=0.79; 95% CI: 0.69-0.91).3 In addition, the number of first and recurrent HF worsening events and CV death was lower with the dapagliflozin group than that in the placebo group in the overall population (HR=0.77; 95% CI: 0.67-0.89; p<0.001), and a group of patients with LVEF <60% (RR=0.77; 95% CI=0.65-0.90; p=0.002).3
On the other hand, patients treated with dapagliflozin were found to have a lower symptom burden, shown by the improvement in total HF symptom score from baseline to month 8 when compared to the placebo group (Win ratio=1.11; 95% CI: 1.03-1.21; p=0.009).3 Overall, the results were comparable for patients with a LVEF ≥60% and those <60%.3 Likewise, the findings were consistent across prespecified subgroups, such as patients with or without diabetes.3 The occurrence of adverse events (AEs) is similar between the 2 study arms.3
In summary, the DELIVER trial demonstrated that dapagliflozin significantly reduces the risk of HF worsening and CV death and is associated with a lower HF symptom burden in patients with HFmEF and HFpEF.3 The findings support wider adoption of dapagliflozin for the treatment of HF patients, regardless of the LVEF.
Understanding the mechanism of benefits of dapagliflozin in HFpEF: An invasive hemodynamic randomized trial
Heart failure with preserved ejection fraction (HFpEF) constitutes >50% of all heart failure (HF) cases, with few effective treatments.1It is known that elevation in left heart filling pressures at rest and during exercise are the pathophysiologic features of HFpEF, andthat sodium-glucose co-transporter-2 inhibitors (SGLT2is), such as dapagliflozin and empagliflozin, have been shown to reduce therisk of HF and cardiovascular (CV) death, while improving the quality of life (QoL) in patients with HFpEF.1 However, the mechanismsbehind this are still unclear.1
Implementation of the 2022 HF guidelines for equitable care
In the American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023 lecture in memory of Dr. Kanu Chatterjee, Dr. Clyde W. Yancy delivered a review on how the 2022 Heart Failure (HF) guidelines will ensure equitable care for all patients in 2023 and beyond.1 The cu
Empagliflozin improves outcomes in HFpEF patients irrespective of age: The EMPEROR-Preserved trial
Recently, the effects of empagliflozin and placebo have been compared in patients with heart failure with preserved ejection fraction (HFpEF), taking age as an account of adverse events (AEs) in the EMPEROR-Preserved trial.1 The results showed that empagliflozin reduced first heart failure hospitalization (HFH) and recurrent HFH.1 The efficacy in different age groups was similar.1 In addition, estimated glomerular filtration rate (eGFR) and health-related quality of life (HRQoL) were investigated.1 It also showed significant efficacy across all age groups on these aspects.1
Pharmacotherapy for HFrEF: A comprehensive network meta-analysis
Globally, approximately 26 million people suffer from heart failure, and an estimated 50% of those cases are heart failure with reduced ejection fraction (HFrEF).1,2 HFrEF patients have seen improvement in the mortality rate, in light of the evolving pharmacological treatment options.3 The utilization of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have readily been employed.1,3-5 Despite the advancements and the availability of a variety of treatments, the mortality rate of individuals with HFrEF remains high.3,6 Therefore, it is necessary to ascertain optimal pharmacological therapy combinations supported by up-to-date global data, with the aim of further reducing HFrEF cases.2 Recent findings by Tromp J and colleagues published in the Journal of the American College of Cardiology: Heart Failure estimated and compared which treatment options are the most advantageous for HFrEF.4
New insights into dapagliflozin: The revolutionary road in diabetic kidney complications
In 2017, approximately 476 million people worldwide were living with diabetes mellitus.1 A study of the International Society of Nephrology revealed that 58% of type 2 diabetes mellitus (T2DM) patients had concomitant chronic kidney disease (CKD), which is also known as diabetic kidney disease (DKD).2 DKD is associated with increased morbidity and mortality risk and has become a huge global burden.3 However, its awareness and diagnosis remain low, and the conventional therapies, such as angiotensin-converting-enzyme inhibitors (ACEIs), lack efficacy data for advanced CKD and are associated with increased risks of hyperkalemia and acute decline in renal function.4,5 Therefore, a novel therapy such as dapagliflozin, an sodium-glucose cotransporter 2 (SGLT2) inhibitor with a prominent reno-protective effect beyond glucose control, is urgently needed. In a recent symposium held virtually in Hong Kong, Professor Mark Cooper shared his insights into the future management of DKD and the exciting results of the DAPA-CKD trial evaluating the long-term efficacy and safety of dapagliflozin in CKD patients with or without T2DM.
Sotagliflozin prevents cardiovascular events regardless of the left ventricular ejection fraction and presence of albuminuria
Type 2 diabetes mellitus (T2DM) is known to be associated with a 33% greater risk of hospitalization for heart failure (HF) and an increase in the risk of cardiovascular and overall death.1 Patients with coexisting T2DM and chronic kidney disease (CKD) are at further risk of HF and ischemic events t
Dapagliflozin as a treatment reduces worsening heart failure and cardiovascular death among heart failure patients
At the 8th Asian Preventive Cardiology & Cardiac Rehabilitation Conference organized by the Hong Kong College of Cardiology, Professor Yu, Cheuk-Man, Director of Heart Centre at Hong Kong Baptist Hospital and Honorary Clinical Professor at The Chinese University of Hong Kong, discussed the role of s
Recalibrating pulmonary vascular resistance to predict heart failure
In patients with pulmonary hypertension, an elevated pulmonary vascular resistance (PVR) of 3.0 Wood units (WU) or more has been known to be associated with poor clinical prognosis.1 In a recent study published in The Lancet