Influence of background medical therapy on efficacy and safety of dapagliflozin in patients with heart failure with improved ejection fraction in the DELIVER trial

Aims

The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial demonstrated the sodium–glucose cotransporter 2 inhibitor dapagliflozin to be beneficial in patients with symptomatic heart failure (HF) with improved ejection fraction (HFimpEF; those with prior left ventricular ejection fraction ≤40% that had improved to >40% by enrolment). Whether this benefit differs by background medical therapy is unclear. The current study aims to determine the efficacy and safety of dapagliflozin among patients with HFimpEF by background medical therapy.

Methods and results

Treatment effects on the primary endpoint (worsening HF or cardiovascular death) were assessed by number of background HF medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor, evidence-based beta-blocker, and mineralocorticoid receptor antagonist). Among the 6263 patients randomized in DELIVER, 1151 (18%) had HFimpEF. Of those, 21% of patients were on 0–1 therapies, 44% were on two therapies, and 35% were on three therapies. During 2.3 years of median follow-up, the incidence rate of the primary outcome was 9.7, 8.8, and 8.4 per 100 person-years for patients on 0–1, 2 and 3 HF medications at baseline, respectively. Treatment effects with dapagliflozin on the primary outcome may be greater in patients with HFimpEF on 0–1 therapies at baseline (p_interaction = 0.09), driven mostly by a significant interaction for HF hospitalization (p_interaction = 0.023) with no evidence of effect modification for cardiovascular death (p_interaction = 0.65). Treatment effects of dapagliflozin on the primary outcome were, however, consistent when assessed across the modified Heart Failure Collaboratory Medical Therapy Score integrating both therapeutic use and dosing (p_interaction = 0.39). The use of dapagliflozin was not associated with changes in use or doses of background HF therapies, and among patients on three HF medications at baseline, the addition of dapagliflozin did not lead to higher adverse events.

Conclusions

In patients with HFimpEF, the safety and efficacy of dapagliflozin were largely similar by background use and dosing of HF medical therapies. The benefit of dapagliflozin in reducing HF events tended to be greater in those patients on 0-1 medications at baseline. Among patients already on three HF medical therapies, the addition of dapagliflozin was safe without requiring de-escalation of other therapies.     

Endobronchial carcinoid presenting as Focal bronchiectasis in a young woman with systemic lupus erythematosus

Non‐resolving pulmonary symptoms in a patient with SLE require evaluation to exclude rare pulmonary lesions, such as carcinoid tumors.     

Renal and blood pressure effects of dapagliflozin in recently hospitalized patients with heart failure with mildly reduced or preserved ejection fraction: Insights from the DELIVER trial

Aims

Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized.

Methods and results

We examined the effects of dapagliflozin versus placebo on estimated glomerular filtration rate (eGFR) slope (acute and chronic), 1-month change in systolic blood pressure, and the occurrence of serious hypovolaemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization. The 654 (90 randomized during hospitalization, 147 1–7 days post-discharge and 417 8–30 days post-discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization (median [interquartile range] 55 [43, 71] vs. 60 [47, 75] ml/min/1.73 m²). Dapagliflozin consistently reduced the risk of all-cause (p_interaction = 0.20), cardiac-related (p_interaction = 0.75), and HF-specific (p_interaction = 0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo-corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (−2.0 [−4.1, +0.1] vs. −3.4 [−3.9, −2.9] ml/min/1.73 m², p_interaction = 0.12). Dapagliflozin's effect to slow chronic eGFR decline was similar regardless of recent hospitalization (p_interaction = 0.57). Dapagliflozin had a minimal effect on 1-month systolic blood pressure and to a similar degree in patients with and without recent hospitalization (−1.3 vs.−1.8 mmHg, p_interaction = 0.64). There was no treatment-related excess in renal or hypovolaemic serious adverse events, irrespective of recent HF hospitalization.

Conclusion

In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on blood pressure and did not increase renal or hypovolaemic serious adverse events, yet afforded long-term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.     

Renewable energy management of an hybrid water pumping system (photovoltaic/wind/battery) based on Takagi–Sugeno fuzzy model

This research work presents an optimal energy management for a hybrid water pumping system driven by a photovoltaic generator (PVG) and a wind turbine. These two renewable energies are used as power generation sources, whereas a battery is added as an energy-storing system, for the purpose of controlling the power flow and providing a constant load supply. The proposed management system, serve to guarantee the pumping system autonomy in a rural region where's no access to the electrical network. As a result, a maximum power point tracking (MPPT) controller is created based on the fuzzy Takagi–Sugeno (TS) model, ensuring maximum power transfer to the moto-pump in spite of wind speed and insolation changes. The synthesis of MPPT control law involves TS fuzzy reference models which generate the desired trajectories to track. A supervisor has been developed for energy management and its major purpose is to effectively use the battery to satisfy the power load requirements, and that is by maintaining the state of charge (SOC) to extend the battery's life. Finally, simulation results have been done based on Matlab/Simulink with the aim of validating the efficiency of the proposed energy management supervisor.