sacubitril and dapagliflozin

To determine the efficacy of sacubitril/valsartan plus dapagliflozin in the treatment of patients with pulmonary arterial hypertension (PAH) due to left heart disease and to explore new treatment regimen for PAH due to left heart disease.. This study is a randomized controlled trial (RCT) study of 120 patients with PAH due to left heart disease admitted to the cardiovascular department of our hospital from Dec. 2019 to Dec. 2021. The patients were randomized 1:1 to the study group and control group. All patients were given baseline treatments targeting left heart disease and symptoms of PAH. In addition to the baseline treatments, patients in the control group were given sacubitril/valsartan tablets, while patients in the study group were given sacubitril/valsartan tablets plus dapagliflozin tablets. After 6 months of treatment, parameters including left heart function and exercise tolerance, Hemodynamics (left ventricular end systolic diameter [LVSED], left ventricular end diastolic diameter [LVEDD], left ventricular ejection fraction [LVEF], 6 min walk distance (6MWD), mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP)), vascular endothelial function (plasma endothelin (ET) -1 and nitric oxide [NO]), heart failure markers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP)], inflammatory factors (serum C reactive protein [CRP], interleukin (IL)-6, and tumor necrosis factor (TNF)-α], and adverse drug reactions (ADRs) were assessed in both groups.. Both groups had reduced LVESD and LVEDD, increased LVEF, and extended 6MWD after 6 months of treatment. The improvements in these parameters were significantly greater in the study group than in the control group (all. Sacubitril/valsartan plus dapagliflozin in the treatment with PAH due to left heart disease can improve left heart function of patients by improving vascular endothelial functions and alleviating inflammation, which helps to reduce the PAH process. Therefore, this combination treatment is safe and effective in PAH due to left heart disease.

Topics: Heart Diseases; Heart Failure; Humans; Pulmonary Arterial Hypertension; Stroke Volume; Valsartan; Ventricular Function, Left

Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice.. This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.. EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose.. Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively.. Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.

Topics: Adrenergic beta-Antagonists; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Drug Combinations; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Tetrazoles; Treatment Outcome; United States; Valsartan

The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II-IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16-3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) (

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Benzhydryl Compounds; Biphenyl Compounds; Drug Combinations; Glucosides; Heart Failure; Humans; Male; Retrospective Studies; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; Ventricular Function, Left

Comorbid heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is associated with a very high risk of HF events. Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improve HF outcomes in these patients, but their comparative value for money in this patient population has not yet been determined.. We aimed to compare the cost needed to treat (CNT) to avoid an HF event with each drug.. CNT was estimated by multiplying the annualized number needed to treat (NNT) to prevent one HF event by the annual cost of each therapy. HF events were defined as the first event of hospitalization for HF or cardiovascular mortality. Drug efficacy data were extracted from published secondary analyses of patients with DM in the DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2021 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed on parameters that may have affected the CNT.. The annualized NNT was 24 (95% confidence interval [CI] 16-54) for dapagliflozin and 57 (95% CI 31-433) for the ARNI. At an annual cost of $US4523 and 5099, respectively, the CNT was $US108,563 (95% CI 72,375-244,267) for dapagliflozin and $US290,671 (95% CI 158,084-2,208,079) for the ARNI.. Dapagliflozin seems to offer greater value for money than the ARNI for patients with HFrEF and DM. Our results provide support for contemporary guidelines advocating the use of dapagliflozin in these patients.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Benzhydryl Compounds; Biphenyl Compounds; Diabetes Mellitus, Type 2; Drug Combinations; Glucosides; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Tetrazoles; Valsartan; Ventricular Dysfunction, Left

The treatment of heart failure with reduced ejection fraction HFrEF (< 40%) uses hygienic-dietary rules combined with beta-blockers, renin-angiotensin system blockers RASB (alone or in combination with Sacubitril) and spironolactone. Dapagliflozin (SGLT2 inhibitor) has proven its effectiveness in reducing morbi-mortality in patients with HF. However, its effects on echocardiographic parameters are less known.. To describe the impact of the addition of Dapagliflozin to conventional treatment on echocardiographic parameters in patients with HFrEF < 40%.. Observational, single-center and non-randomized study involving patients with HFrEF < 40%. This group was compared to a cohort of 50 patients with HfrEF < 40% under conventional treatment without Dapagliflozin (taken from the HF register of our center and whose management dates back to before the adoption of this molecule in the HF ESC-2021 guidelines) to assess the ultrasound impact of Dapagliflozin.. 43 patients aged between 40 and 68 years with HfrEF < 40% on Beta-blocker, BSRA, Spironolactone and Dapagliflozin 10 mg/d. The mean EF was 33% ± 3 (30-39%), mean LVd diameter 64 mm ± 6 (55-71 mm) and mean longitudinal strain at -11% ± 4. These patients were compared to a cohort of 50 patients with the same profile without Dapagliflozin. After a follow-up of 7 months (5-8 months): The average EF increased to 37% with 11 patients EF > 40% against 35% and 5 patients EF > 40% for the group without Dapagliflozin (P 0.057), average LVd at 61 mm versus 66 mm in the group without Dapagliflozin (P 0.095), Mean longitudinal strain at -14% (6 patients < -15) versus -12% (1 patient <-15) in the group without Dapagliflozin (P 0.046).. In a population of patients with HfrEF < 40% under conventional treatment for HF, the prescription of Dapagliflozin is associated with an improvement of echocardiographic parameters (EF and longitudinal strain). MOTS-CLéS: Série;Dapagliflozine;insuffisance cardiaque;strain;ProBNP;dysfonction VG.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aminobutyrates; Benzhydryl Compounds; Biphenyl Compounds; Echocardiography; Glucosides; Heart Failure; Humans; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors; Spironolactone; Stroke Volume

The effects of adding a sodium-glucose cotransporter 2 (SGLT2) inhibitor to a mineralocorticoid receptor antagonist (MRA) or an angiotensin receptor-neprilysin inhibitor (ARNI) in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are uncertain, even though the use of all three drugs is recommended in recent guidelines.. The efficacy and safety of dapagliflozin added to background MRA or ARNI therapy was examined in patients with HFmrEF/HFpEF enrolled in the DELIVER trial. The primary outcome was the composite of worsening HF or cardiovascular death. Of 6263 patients, 2667 (42.6%) were treated with an MRA and 301 (4.8%) with an ARNI at baseline. Patients taking either were younger, more often men and had lower systolic blood pressure and ejection fraction; they were also more likely to have prior HF hospitalization. The benefit of dapagliflozin was similar whether patients were receiving these therapies. The hazard ratio for the effect of dapagliflozin compared to placebo on the primary outcome was 0.86 (95% confidence interval [CI] 0.74-1.01) for MRA non-users versus 0.76 (95% CI 0.64-0.91) for MRA users (p. The efficacy and safety of dapagliflozin were similar, regardless of background treatment with an MRA or ARNI. SGLT2 inhibitors may be added to other treatments recommended in recent guidelines for HFmrEF/HFpEF.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Hypotension; Male; Mineralocorticoid Receptor Antagonists; Stroke Volume; Tetrazoles; Valsartan

The Angiotensin Receptor-Neprilysin Inhibitor sacubitril-valsartan (ARNI) and dapagliflozin, a sodium-glucose transport protein 2 inhibitor, reduce the risk of heart failure hospitalization (hHF) and cardiovascular (CV) mortality in patients with reduced ejection fraction (HFrEF). Their comparative value for money is undetermined. Therefore, our aim was to compare the cost per outcome implications of utilizing dapagliflozin vs. ARNI for preventing heart failure (HF) events of non-diabetic patients with HFrEF.. We calculated the cost needed to treat (CNT) to prevent one HF event. The cost needed to treat was estimated by multiplying the annualized number needed to treat (NNT) to prevent one event by each therapy's annual cost. Efficacy estimates were extracted from published secondary analyses of non-diabetic patients in DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2020 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the trial's populations and drug costs in various countries.The annualized NNT to prevent one HF event for dapagliflozin was 31 (95% CI 21-71) vs. 33 (95% CI 24-62) for ARNI. The CNT of dapagliflozin in the US is $141 112 (95% CI $95 592-$323 192) compared to $158 169 (95% CI $115 032-$297 166) for sacubitril-valsartan. The CNT results were sensitive to drug costs in various countries.. Dapagliflozin and ARNI provide comparable value for money for preventing HF events in non-diabetic patients with HFrEF. In healthcare settings where dapagliflozin's price is significantly lower than ARNI, it provides superior value for money.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Benzhydryl Compounds; Biphenyl Compounds; Drug Combinations; Glucosides; Heart Failure; Humans; Stroke Volume; Treatment Outcome; Valsartan