Effect Of Dapagliflozin In Patients Research Articles

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p < 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p < 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p < 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Clinical and economic analysis of the use of dapagliflozin in patients with chronic heart failure with reduced left ventricular ejection fraction in various subgroups of standard therapy in the Russian Federation

To evaluate the clinical and economic effectiveness of dapagliflozin in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (HFrEF) in the Russian Federation in various subgroups of standard therapy for CHF. A clinical and economic analysis of the use of the drug dapagliflozin in addition to standard therapy was carried out in comparison with standard therapy in various subgroups of standard therapy for HFrEF using a modeling method. Cost calculations were carried out in a mathematical model adapted to the healthcare conditions of the Russian Federation by using Russian cost indicators and characteristics of the patient population. The present study demonstrates that the addition of dapagliflozin is beneficial in terms of clinical and cost-effectiveness, regardless of the initial regimen (angiotensin receptor-neprilysin inhibitors [ARNI] or angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]) of standard drug therapy for HFrEF and in all cases leads to an increase in life expectancy, a decrease in the number of hospitalizations and emergency visits due to CHF, as well as cardiovascular mortality. The obtained values of added value per additional year of life in all cases are significantly lower than the willingness-to-pay threshold, which indicates the clinical and economic effectiveness of the strategy of prescribing dapagliflozin as part of standard therapy for patients with HFrEF. In the case of adding dapagliflozin the values of the additional cost of an added year of life in the 3 considered standard therapy options (ARNI or ACEi/ARB, only ACEi/ARB and only ARNI) were 291,256, 279,571 and 338,374 rubles respectively. Thus, the scenario of using dapagliflozin with standard therapy, which included only ACEi/ARB, is characterized by the lowest additional cost and has the best clinical and economic characteristics. At the same time the scenario of use with standard therapy, which included only ARNI, is characterized by the highest value of the additional value of the added year of life.

The Impact of Genetic Polymorphisms on the Anti-Hyperglycemic Effect of Dapagliflozin.

The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM). A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin. Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45-10.71) mmol/L vs 6.40 mmol/L (5.45-9.20) mmol/L, p = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88-10.00)% vs 8.10% (6.83-10.00)%, p = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote (p = 0.014, p = 0.024, and p = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs-rs12471030, rs12988520 and rs2602381-were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment. After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population. ChiCTR2200059645.

#150 Effect of dapagliflozin in patients with CKD depending on primary kidney disease

Abstract Background and Aims Multiple trials have reported that SGLT2 inhibitors reduce the risk of its primary composite outcome of kidney disease progression or cardiovascular death in a wide range of patients with CKD. Our aim was to compare effects on kidney outcomes among the different types of kidney diseases. Method Eligible patients with eGFRs ≥30-45, or ≥45-90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio of ≥300 mg/g, and receiving renin angiotensin system inhibitor, where indicated and tolerated were randomized to dapagliflozin 10 mg once daily vs placebo. Kidney disease progression was defined as a sustained ≥30% eGFR decline from randomization or to &amp;lt;10 mL/min/1.73 m2, start of maintenance dialysis or receipt of a kidney transplant, or renal death, and the effects of dapagliflozin were analyzed using a pre-specified Cox model. Testing for heterogeneity of effect between pre-specified kidney disease subgroups was performed, including exploratory analyses by specific glomerular disease etiologies. Results 362 participants were followed for a median of 2.0 years. 90 (24.8%) had diabetic kidney disease, 126 (34.8%) had glomerular disease, 94 (26%) had hypertensive or renovascular disease, and 52 (14.4%) had other or unknown causes. Overall, dapagliflozin reduced the risk of kidney disease progression by 34% (dapagliflozin 29/178 vs placebo 48/184; hazard ratio 0.62, 95% CI 0.51-0.78). This relative risk reduction appeared broadly similar in subgroup analyses by primary cause of kidney disease and by different types of glomerular disease. Conclusion Our study with a few numbers of patients with diabetic and non-diabetic causes of CKD showed that dapagliflozin reduced risk of kidney disease progression with relative risk reductions that were broadly similar across the different CKD etiologies.

Effect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose-lowering therapy: A pre-specified analysis of the DELIVER trial.

Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain. DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre-specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow-up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50-1.00; 1 GLT: HR 1.04, 95% CI 0.80-1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56-0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59-0.92) and without background metformin use (HR 0.89, 95% CI 0.72-1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69-1.16) and without background insulin use (HR 0.78, 95% CI 0.65-0.95; pinteraction = 0.45). Dapagliflozin was well-tolerated irrespective of the number of background GLTs. Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first-line SGLT2i among individuals with T2D and HF, irrespective of background GLT.

«Назначить нельзя не назначить»: роль β-блокаторов в современном лечении пациента с артериальной гипертонией и сопутствующими заболеваниями

The paper is focused on clarifying the role of using β-blockers in modern treatment of arterial hypertension (AH) in patients with comorbidities. Despite the fact that the majority of clinical guidelines on the treatment tactics for AH consider β-blockers as the drugs prescribed when there are certain additional indications, nowadays an attempt is made to return to the distant past of cardiology, when β-blockers played a role of first line antihypertensive drugs. The paper provides evidence-based arguments in favor of the balanced approach to prescription of β-blockers to patients with AH. At the same time, the paper presents the results of the recent analysis involving the data on the participants of the large randomized trial focused on assessing the effects of dapagliflozin in patients with heart failure and preserved left ventricular ejection fraction suggesting frequent use of β-blockers in clinical practice for patients with AH and concomitant disorders, as well as the β-blockers’ safety and probable efficacy. The paper provides the meta-analysis results allowing one to estimate antihypertensive effect of β-blockers, the use of which makes it possible to reduce systolic blood pressure by almost 8—10 mm Hg. Furthermore, the paper discusses an opportunity to quickly obtain information about the role of certain drugs for treatment of AH using ChatGPT that is considered to be a promising information technology. The paper also provides data on the use of the doses of β-blockers that are not high enough and does not allow to achieve optimal heart rate in clinical practice.

Effects of Dapagliflozin in Patients with Membranous Nephropathy.

Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial. Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR. Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m2, and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event. In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.

The association of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients with diabetic nephropathy and essential hypertension

Objective — to establish possible associations of rs4646994 ACE and rs1799983 eNOS gene polymorphisms with metabolic effects of dapagliflozin in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. Clinical investigation and examinations involved 171 pts, from them 85 (49.7%) females and 86 (50.3%) males with DN of I—IV stages and EH of II—III stages, aged 31 to 82 years old (an average age was 59.38±1.58 years). They were also genotyped for rs4646994 (I/D) ACE and for rs1799983 (G894T) eNOS gene polymorphisms with the use of polymerase chain reaction. Among the patients with I/D polymorphism of ACE gene there were 24 (14.0%) pts with genotype II, 32 (18.7%) pts with genotype ID and 26 (15.2%) subjects with genotype DD. Among the participants with G894T eNOS gene polymorphism GG genotype was revealed in 29 (16.9%) pts, GT genotype was found in 33 (19.3%) cases and 27 (15.8%) examined persons had TT genotype. Standard parameters of lipid profile were measured in all included pts with a use of an immune enzyme method. Glucose oxidase and immune enzyme methods were used to define serum glucose and insulin levels; level of glycosylated hemoglobin (HbA1C) was detected by fluid chromatography method. Insulin resistance (IR) indices such as HOMA‑IR, triglyceride‑glucose index (TGGI), METS‑IR (metabolic score for insulin resistance) index were calculated by known formulas. Cardiometabolic risk (CMR) of the pts was estimated by ­METS‑IR index. Body mass index (BMI), body fat percentage (BFP), total fat mass (TFM) and fat mass index (FMI) in all the pts were calculated by standard known formulas. Serum uric acid concentration was measured with phosphovolframic method. Dapagliflozin 10 mg/daily was added for 24 weeks to the basic standard antidiabetic therapy including gliclazide or glimepiride and metformin combined with lipid lowering therapy containing atorvastatin. The standard therapy was not changed during the whole period of observation.&#x0D; Results. No association has been revealed between I/D ACE and G894T eNOS gene polymorphisms in pts with DN and EH, with a noted improvement of lipid blood spectrum due to administration of dapagliflozin in a dose of 10 mg/daily for 24 weeks. It has been established that allele D was associated with a reduction of dapagliflozin efficacy in the correction of carbohydrate metabolism disorders in pts with DN and EH. At presence of allele D (ID and DD) in genotype, the levels of glycemia, insulinemia, HbA1C, IR indices such as HOMA‑IR, TGGI, METS‑IR decreased less effective than in the case of allele D absence (genotype II). In pts with DN and EH who had G894T eNOS gene polymorphism, dapagliflozin 10 mg/daily improved muscle sensitivity to insulin and decreased CMR depended on genotype in the following order: GT &gt;TT &gt;GG, whereas the intensity of glycemia, insulinemia, HbA1C and HOMA‑IR index reduction was found to be associated with genotype as follows: GG &gt;GT &gt;TT. Allele I compared with allele D of I/D ACE gene polymorphism in pts with DN and EH was revealed to be associated with more significant reduction of BFP, TFM and FMI due to dapagliflozin administration. In pts with DN and EH who had G894T eNOS gene polymorphism dapagliflozin 10 mg/daily reduced a body mass due to its influence on fat accumulation but not on muscle tissue both in phenotype of visceral obesity (genotype GG) and in phenotype of sarcopenic obesity (genotype GT). In the realization of hypouricemic effects of dapagliflozin in patients with DN and EH, both genetic factors (D and T alleles of I/D ACE and G894T eNOS gene polymorphisms correspondingly), and metabolic factors (initial levels of HbA1C and UA together with anthropometric parameters characterized visceral obesity phenotype such as BMI, TFM and FMI) were involved.&#x0D; Conclusions. In pts with DN and EH, the association of I/D ACE (rs4646994) and G894T eNOS (rs1799983) gene polymorphisms with metabolic effects of dapagliflozin 10 mg/daily has been established. A presence of allele D of I/D ACE and allele T of G894T eNOS gene polymorphisms in genotype was concluded to be associated with less significant metabolic effects of dapagliflozin compared with an absence of these alleles in genotype.&#x0D;

Heart Failure, Investigator-Reported Sleep Apnea and Dapagliflozin: A Patient-Level Pooled Meta-Analysis of DAPA-HF and DELIVER

Sleep apnea is more common in patients with heart failure (HF) than in the general population, but little is known about its association with clinical outcomes in various HF phenotypes or how it might modify the effect of HF therapy. To examine the prevalence of sleep apnea, its association with outcomes and the effects of dapagliflozin in patients with HF with and without sleep apnea in a pooled analysis of 2 trials comparing dapagliflozin to placebo in HFrEF (DAPA-HF trial) and HFmrEF/HFpEF (DELIVER trial). A history of sleep apnea was investigator-reported. The primary outcome was a composite of worsening HF or cardiovascular death. The prevalence of sleep apnea was 5.7% and 7.8% in patients with HFrEF and HFmrEF/HFpEF, respectively. The primary outcome occurred at a rate of 16.0 in participants with sleep apnea compared to 10.6 per 100 person-years in those without (adjusted HR 1.29 [95%CI, 1.10-1.52]). Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients with (HR 0.78 [95% CI, 0.59-1.03]) and without sleep apnea (HR 0.79 [0.72-0.87]) [Pinteraction = 0.93]. The beneficial effects of dapagliflozin on other clinical outcomes and symptom burden, physical function, and quality of life were consistent in participants with and without sleep apnea. In DAPA-HF and DELIVER, the true prevalence of sleep apnea was likely underestimated. An investigator-reported history of sleep apnea was associated with higher rates of worsening HF events. The benefits of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. Unique identifiers: NCT01920711 CONDENSED ABSTRACT: In a pooled analysis of the DAPA-HF and DELIVER trials of more than 11,000 patients with heart failure (HF) across the range of ejection fractions, an investigator-reported history of sleep apnea was associated with higher rates of worsening HF events but not mortality. The beneficial effects of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. These findings provide further evidence for dapagliflozin as a new treatment option for patients with heart failure across the range of ejection fractions.

Effects of Dapagliflozin in Patients in Asia: A Post Hoc Subgroup Analysis From the DELIVER Trial

BackgroundPatients with heart failure (HF) with mildly reduced or preserved ejection fraction in Asia may have different clinical characteristics and outcomes compared with patients from other parts of the world. ObjectivesThe purpose of this study was to investigate the clinical characteristics, safety, and efficacy of dapagliflozin in patients in Asia vs outside Asia in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial. MethodsIn the DELIVER trial, patients with HF and left ventricular ejection fraction >40% were enrolled across 353 sites in 20 countries. The effects of dapagliflozin vs placebo on primary (composite of worsening HF or cardiovascular death) and secondary outcomes were compared in patients from Asia vs outside Asia. ResultsAmong 6,263 participants, 1,226 (19.6%) were enrolled in Asia. Participants from Asia were less likely to have diabetes, hypertension, history of myocardial infarction, or obesity. After adjusting for clinically relevant characteristics, those in Asia had similar risks of primary composite outcome compared with those from outside Asia (HR: 0.97; 95% CI: 0.82-1.15). Those in Asia had a lower risk of all-cause mortality compared with those enrolled outside Asia (HR: 0.54; 95% CI: 0.44-0.66). Enrollment from Asia did not modify the effect of dapagliflozin on the primary outcome (Pinteraction = 0.54). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs outside Asia. ConclusionsIn the global DELIVER trial, dapagliflozin reduced the risk of CV death or worsening HF events and was well tolerated among participants enrolled in both Asia and other geographic regions.

Effect of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction treated with beta-blockers: the DELIVER trial

Abstract Background While beta-blockers are not recommended for the treatment of HFpEF according to the latest ESC and AHA/ACC/HFSA guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers might adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Purpose To examine the contemporary use and implications of beta-blocker use in patients with HFmrEF or HFpEF. Methods In the DELIVER trial, a total of 6,263 patients with symptomatic HF with LVEF &amp;gt;40% were randomized to dapagliflozin or placebo across 20 countries. Efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results Overall, beta-blockers were used in 5,177 patients (83%), with wide variation ranging from Mexico (60%) to Poland (93%). Nearly all patients taking beta-blockers had at least 1 potential indication (n = 5,106 [99%]), such as hypertension (n = 4,623 [89%]), atrial fibrillation/flutter (n= 2,969 [57%]), coronary artery disease (n= 2,744 [53%]), or previous LVEF&amp;lt; = 40% that has since improved (n = 991 [19%]). Beta-blocker use was not associated with a higher risk of the primary outcome in covariate-adjusted models (HR 0.68 [95% CI 0.59-0.80]; Left Panel). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR 0.82 [95% CI 0.72- 0.94]) and those not taking beta-blockers (HR 0.79 [95% CI 0.61-1.03]; P for interaction = 0.85), with similar findings for key secondary endpoints (Right Panel). Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions In patients with HFmrEF or HFpEF enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker, with virtually all these patients having at least 1 potential indication for use. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.

Effect of dapagliflozin in patients in Asia with heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER

Abstract Background A large and growing fraction of the global heart failure (HF) population lives in Asia. One-fifth of participants in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial were enrolled from Asia, providing a rich source of contemporary data to understand their unique clinical profiles and responses to sodium-glucose cotransporter 2 (SGLT2) inhibition. Purpose To assess the differences in clinical characteristics, outcomes, and response to dapagliflozin in patients from Asia vs outside Asia among patients with HF with mildly reduced or preserved ejection fraction in the DELIVER trial. Methods DELIVER was a global randomized clinical trial enrolling across 353 sites in 20 countries. Baseline clinical characteristics from patients enrolled in DELIVER trial were compared between patients in Asia vs outside Asia. The primary outcome was a composite of worsening HF or cardiovascular (CV) death. The effect of dapagliflozin on primary and secondary outcomes were compared in patients in Asia vs outside Asia. Results Among 6,263 participants in the DELIVER trial, 1,226 (19.6%) were enrolled in Asia (310 in China, 422 in Japan, and 318 in Taiwan, and 176 in Vietnam). Compared to patients outside Asia, participants from Asia were similar in age, more likely to be men with previous HF hospitalization, less likely to have obesity, diabetes, hypertension, or history of myocardial infarction, and had lower symptom burden despite similar natriuretic peptide levels (Figure 1). After adjusting for age, sex, and baseline LVEF, those in Asia faced similar risks of HF events but lower risk of mortality compared with those enrolled outside Asia (all-cause mortality Asia vs. outside Asia: HR 0.60, 95% confidence interval [CI] 0.49 – 0.72, Table 1). Within Asia, all-cause mortality was highest in Vietnam (6.8 per 100 person-year [py]), followed by Taiwan (6.7 per 100 py), Japan (3.5 per 100 py) and China (3.3 per 100 py). Dapagliflozin reduced the primary outcome in participants enrolled in Asia (hazard ratio [HR] 0.89, 95% CI 0.67-1.18) and outside Asia (HR 0.80, 95% CI 0.71 – 0.92) to a similar extend (P-interaction = 0.54, Figure 1). Similarly, region did not modify the treatment effect of dapagliflozin on CV death, HF hospitalization, all-cause death, CV death and recurrent HF events, or changes in Kansas City Cardiomyopathy Questionnaire scores (P-interaction &amp;gt; 0.30 for all). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs. outside Asia. Conclusions In the global DELIVER trial, dapagliflozin reduced the risk of CV death or HF events and was well tolerated both among participants enrolled in Asia and other geographic regions.Figure 1Table 1

Mediators of the Kidney Protective Effects of Dapagliflozin in Patients with CKD with or Without Type 2 Diabetes

Mediators of the Kidney Protective Effects of Dapagliflozin in Patients with CKD with or Without Type 2 Diabetes

Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Heart failure (HF) is a major cause of recurrent hospitalization and death worldwide. Sodium-glucose cotransporter-2 inhibitors including dapagliflozin are anti-diabetic drugs with promising cardiovascular (CV) effects. We performed systematic review and meta-analysis of randomized controlled trials investigating the effects of dapagliflozin in heart failure patients. We searched PubMed, Scopus and ScienceDirect databases. A total of 1,567 studies from January 2017 to September 10, 2022, were screened. After applying exclusion criteria, 22 studies were retrieved for full-text screening, and nine of them were eligible for this meta-analysis. Effect estimates for dichotomous variables were expressed as risk ratio (RR) and 95% CI. The primary outcomes were the incidence of all-cause mortality, hospitalization due to HF, and CV death. This review was registered on PROSPERO with ID CRD42022347793. A total of 14,032 patients were included. The overall risk ratio of all-cause mortality favored the dapagliflozin group over the placebo/standard therapy group (RR = 0.89, 95% CI: 0.82-0.97, P = 0.006) and the pooled studies were not heterogenous (I2 = 0%). Additionally, dapagliflozin significantly reduced the hospitalization due to heart failure (RR = 0.76, 95% CI: 0.70-0.84, P > 0.00001, I2 = 0%), cardiovascular death (RR = 0.87, 95% CI: 0.78-0.97, P = 0.01, I2 = 0%) and their composite outcomes. Dapagliflozin reduces the risk of all-cause mortality, heart failure hospitalizations and cardiovascular death in a wide range of heart failure patients.

#5217 PROTOCOL AND PRELIMINARY RESULTS OF DAPAGLIFLOZIN IN INACTIVE LUPUS NEPHRITIS CROSS-OVER RANDOMIZED TRIAL

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) with and without type 2 diabetes. Lupus nephritis (LN) patients under immunosuppression were excluded from the most important trials with SGLT2 inhibitors. Thus, efficacy and tolerance of these drugs are unknown in such patients. The present trial will assess the effect of Dapagliflozin in patients with inactive Lupus Nephritis with residual proteinuria. Method For this cross-over randomized trial, we will include adult patients with LN class III, IV (+/-V) without active nephritis but with proteinuria &amp;gt; 500mg/24h or UPC &amp;gt; 200mg/g and eGFR ≥ 20ml/min, in the maintenance treatment. RAAS inhibition should be stable for at least four weeks before the randomization. We will exclude patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI&amp;gt;2), use of induction therapy in the last 12 months (Cyclophosphamide, Mycophenolate Mofetil &amp;gt;2 g/day and Calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we will exclude patients with recurrent urinary infections (&amp;gt;3 times/year). They will be randomized to receive Dapagliflozin 10mg on top of standard of care therapy or not. After 24 weeks the groups will be switched and those without Dapagliflozin will receive it for the next 24 weeks. Primary endpoint will be reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints will include sustained reduction of eGFR &amp;gt; 30%; changes in weight and blood pressure compared to baseline; and number of infections on Dapagliflozin treatment versus exclusive standard of care therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05). Results From 85 screened class III, IV (+/- V) LN patients under maintenance therapy, we excluded 65 due to active nephritis, low proteinuria or low eGFR. Until now we included 17 patients that were randomized 1:1 to start the treatment with Dapagliflozin on top of standard care or remain with the usual therapy for 24 weeks. Patients’ baseline characteristics are described in Table 1. All patients randomized were using Mycophenolate Mofetil ≤2 g/day and RAAS inhibition and 14 of them were receiving Hydroxychloroquine. Conclusion We expect that the present trial will determine whether the SGLT2 inhibitor Dapagliflozin, added to LN maintenance therapy, could safely reduce the residual proteinuria of inactive LN patients.

58. Blood Pressure Reduction Effect of Dapagliflozin in Patients with Type 2 Diabetes Mellitus: a Systematic Review

Hypertension is a common comorbidity in patients with Type 2 Diabetes Mellitus (T2DM). One of the new anti-diabetic classes is Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor which is still widely tested in clinical trials for indications beyond T2DM. However, the effect on blood pressure in T2DM patients receiving SGLT2 inhibitors is still not well known. This study wants to find out the effect of Dapagliflozin on blood pressure in patients with T2DM. This study was conducted on 1–7 January 2023. Two independent researchers systematically extracted data from several databases, such as PubMed Central (PMC), Science Direct, and PUBMED by using MeSH terminology of keywords SGLT2 inhibitor and blood pressure. The extracted studies were then analyzed and selected according to our inclusion criteria such as studies in the last 5 years, T2DM patients receiving dapagliflozin, cohort studies, and case-control studies. We excluded systematic reviews, meta-analyses, case series, case reports, studies on pregnant women, children, and animals. Research quality was assessed using Newcastle-Ottawa (NOS). From 4 cohort studies (1664 subjects from various countries), all of them showed dapagliflozin administration resulted in reduction of systolic blood pressure. In some studies, the blood pressure-lowering effect of dapagliflozin administration was greater when combined with other classes of anti-diabetic drugs like Glucagon-Like Peptide-1 (GLP1) agonist; All studies have proven good quality based on NOS. In conclusion, dapagliflozin had a blood pressure-lowering effect in T2DM patients. However, further study is needed to confirm these findings.

Nephroprotective Effects of Dapagliflozin in Patients with Type 2 Diabetes.

Objective This study analyzed changes in the estimated glomerular filtration rate calculated using cystatin C (eGFRcys) and sodium excretion in the urine after administering dapagliflozin as an add-on therapy to conventional treatment for diabetes. Methods This was a single-center, single-group, prospective interventional study. Dapagliflozin was administered to improve the plasma glucose control in 30 subjects with type 2 diabetes mellitus (age 53±8 years old; 66.6% men). Blood and urine tests were performed before and 6 and 12 months after dapagliflozin administration. The daily sodium excretion was estimated with the Kawasaki formula using second-morning urine samples. Results The eGFRcys did not markedly differ before and 6 months after the dapagliflozin administration but was significantly increased after 12 months (p<0.001), and the estimated daily sodium excretion was also significantly increased (p<0.001 at 6 months and p=0.002 at 12 months). The systolic and diastolic blood pressures tended to decrease after administration. The HbA1c level after the administration of dapagliflozin tended to be lower in the T3 group, showing the smallest increase in changes in the estimated daily sodium excretion from baseline to 6 months (28.2-107.5 mEq/day), than in the combined groups of T1 (219.5-110.1 mEq/day) and T2 (101.4-28.9 mEq/day). In contrast, the eGFRcys was significantly higher in the combined groups of T1 and T2 than that in the T3 group at both 6 and 12 months (p=0.031 and p=0.007, respectively). Conclusions Add-on therapy with dapagliflozin increased the urinary sodium excretion and decreased the blood pressure even in the early phase of this therapy. Our results suggest that dapagliflozin add-on therapy may exert nephroprotective effects in subjects with type 2 diabetes mellitus.

PS-C26-7: A SINGLE-CENTER, RETROSPECTIVE STUDY OF BLOOD PRESSURE EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Backgrounds: Sodium-glucose transporter 2(SGLT2) inhibitors are reported to have blood pressure lowering effects in addition to glucose-lowering effects. Previous studies have shown SGLT2 inhibitors, including dapagliflozin, reduce systolic blood pressure among patients with type 2 diabetes. Its mechanism is still uncertain; however, previous studies suggest plasma reduction by osmotic diuresis and natriuresis may contribute to lowering blood pressure. Dapagliflozin was recently approved as the treatment for chronic kidney disease in Japan. Blood-pressure lowering effects of SGLT2 inhibitors among patients with chronic kidney disease (CKD) are still unknown; therefore, we investigated blood-pressure effects of dapagliflozin in patients with CKD. Design and method: Patients with chronic kidney disease (estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2, or markers of kidney damage, or both, of at least 3 months duration) were given 10 mg dapagliflozin daily for at least 4 weeks. Patients who had any changes in their antihypertensive drug prescription during this observation period were excluded. Clinical data including blood pressure measurements, eGFR, urine protein/creatinine ratio, and urinary sodium excretion before and after administration were taken and compared. Results: Contrary to previous reports, there was no significant difference in blood pressure at two months after administration. However, there was a trend of blood pressure decline at four months. Since this study is retrospective, measurement procedures were not aligned among patients, and body fluid evaluation was not considered. These inconsistent conditions may have affected the results. Also, dapagliflozin was administered to most patients in this study at the end of fall or beginning of winter, as it was approved for CKD patients in Japan in August 2021. Decreasing temperature may have limited or countervailed the blood pressure lowering effect of dapagliflozin in the first two months. Conclusions: Our findings indicate that the use of Dapagliflozin may serve as adjunct blood pressure lowering therapy in patients with CKD. Prospective study is needed to further investigate the blood pressure effects of dapagliflozin in CKD patients.

Клинические эффекты дапаглифлозина у лиц с сахарным диабетом 2 типа и пароксизмальной формой фибрилляции предсердий

Клинические эффекты дапаглифлозина у лиц с сахарным диабетом 2 типа и пароксизмальной формой фибрилляции предсердий

The Clinical Effect of Dapagliflozin in Patients with Angiographically Confirmed Coronary Artery Disease and Concomitant Type 2 Diabetes Mellitus

Nowadays treatment of patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (DM) needs further study.&#x0D; The aim. Evaluation of the clinical effect and glycemic variability of dapagliflozin in patients with angiographically confirmed CAD and concomitant type 2 DM.&#x0D; Materials and methods. The study involved 47 patients with angiographically confirmed CAD. The patients underwent laboratory blood tests, electrocardiography, echocardiography, continuous glucose monitoring and percutaneous coronary intervention (PCI). Depending on the usage of dapagliflozin 10 mg, the patients were divided into 2 groups: group I (+SGLT2i, n = 24) and group II (–SGLT2i, n = 23). The average follow-up period was 16 months.&#x0D; Results. Distribution of the examined patients by age, anthropometric characteristics, duration of DM, functional state of the heart and kidneys, smoking, the presence of acute cardiovascular events and previous PCI showed no statistically significant difference. In patients of group I, on the background of taking SGLT2i, a decrease in body mass index and improved glycemic profile were revealed. Patients in group II were more likely to have complaints of angina (4 [17.3%] vs 1 [4.3%], p&gt;0.05); repeated coronary angiography in this group was significantly more likely to reveal progression to atherosclerotic CAD (4 [17.3%], p&lt;0.05) which required re-revascularization. No fatalities were detected during the follow-up.&#x0D; Conclusion. Dapagliflozin has improved glycemic and lipid profile of the blood and long-term prognosis after PCI. Adding this drug to the treatment reduces the clinical progression of CAD, the need for re-hospitalization and cardiac revascularization.