scholarly journals The effects of dapagliflozin on kidney and cardiovascular outcomes in patients with chronic kidney disease with and without heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J L Heerspink ◽  
D C Wheeler ◽  
P Vart ◽  
N Jongs ◽  
F F Hou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Premature Mortality ◽  
Cardiovascular Death ◽  
Private Company ◽  
Double Blind ◽  
Funding Sources

Abstract Background Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and the severity of kidney impairment increases risk of HF, highlighting the deleterious interplay between the conditions. The DAPA-CKD trial showed that dapagliflozin reduced the risk of kidney failure and HF hospitalization in patients with CKD. Purpose This prespecified analysis of DAPA-CKD aimed to determine the effects of dapagliflozin on kidney, cardiovascular and mortality outcomes according to presence or absence of HF. Methods DAPA-CKD (NCT03036150) was a randomized, double blind, controlled trial, which enrolled 4,304 participants with CKD. Participants were randomized to dapagliflozin 10 mg/day or placebo, as adjunct to standard care, and were followed for a median 2.4 years. The primary endpoint was a composite of sustained decline in eGFR ≥50%, end-stage kidney disease, or renal or cardiovascular death. Key secondary endpoints included a composite of cardiovascular death or HF hospitalization and all-cause mortality. Results Overall, 468 (11%) participants had a HF diagnosis at baseline. Participants with HF were older (65.3 vs 61.4 years) and more frequently diagnosed with type 2 diabetes (77% vs 66%) compared with those without HF; mean eGFR was similar (43.2 vs 43.1 mL/min/1.73m2) in the two groups. The primary outcome occurred more frequently in those with versus without HF (8.8 vs 5.7 events per 100 patient-years, respectively). The effect of dapagliflozin on the primary outcome was consistent among those with (hazard ratio [HR] 0.58; 95% CI 0.37, 0.91) or without HF (HR 0.62; 95% CI 0.51, 0.75; p-interaction 0.59). The composite of cardiovascular death or HF hospitalization (HR 0.68; 95% CI 0.44, 1.05 vs 0.70; 95% CI 0.51, 0.97; p-interaction 0.90), and the relative risk reduction for mortality (HR 0.56; 95% CI 0.34, 0.93; vs 0.73; 95% CI 0.54, 0.97; p-interaction 0.39) were also consistent in those with or without HF. Conclusion Patients with co-existing CKD and HF are at high risk of kidney and cardiovascular events and premature mortality. Dapagliflozin consistently reduced the proportional risk of these events, regardless of the presence or absence of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

scholarly journals Clinical course and related costs of patients with diabetes and heart failure and/or chronic kidney disease, drawn from a sample of more than 7 million people

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.P Maggioni ◽  
C Piccinni ◽  
S Calabria ◽  
L Dondi ◽  
G Ronconi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Metabolic Diseases ◽  
Clinical Epidemiology ◽  
Community Setting ◽  
Private Company ◽  
Funding Sources ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Background Diabetes (T2DM), heart failure (HF) and chronic kidney disease (CKD) are among the leading causes of mortality and hospitalization worldwide. This analysis of the Ricerca e Salute (ReS) database is aimed to describe clinical epidemiology, 2-year outcomes and direct costs of T2DM patients with HF, CKD or both in a community setting. Methods Analyses were performed on the ReS database including 7,365,716 subjects. During 2015, subjects with T2DM were selected and subsequently split in the following mutually exclusive cohorts (Figure): – “healthy” T2DM patients, subjects with T2DM but without coronary artery disease (CAD), HF, stroke, TIAs, peripheral artery disease (PAD) and CKD. – Patients affected by T2DM and HF. – Patients affected by T2DM and CKD. – Patients affected by T2DM and both HF and CKD. Results Table shows the baseline characteristics, hospitalization reasons, and related costs of the 4 cohorts. In the 2-year follow-up, T2DM patients with comorbidities are older, more frequently males, and more often admitted for CV and renal reasons. T2DM patients with both HF and CKD have the worst outcome profile. The cost per patient per year is 5 times more for T2DM patients with both HF and CKD than for those with T2DM without these comorbidities. Conclusions Coexistence of HF and/or CKD in patients with T2DM ia associated with a very high clinical and economical burden. Instead of treating each condition individually, the most appropriate approach should be to adopt a collaborative approach that embraces CV, renal and metabolic diseases. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was partially supported by an unrestricted grant from Astra Zeneca. Astra Zeneca was not involved in data collection, analysis and interpretation, in writing the report, nor in deciding to submit the article for publication.

scholarly journals The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study

2021 ◽  
Vol 93 (6) ◽  
pp. 713-723
Author(s):  
Mikhail M. Batyushin
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Double Blind ◽  
Stage Renal Disease ◽  
End Stage

Aim. The article presents the main results of a randomized, double-blind, parallel, placebo controlled trial of DAPA-CKD. Materials and methods. The study included patients with chronic kidney disease (CKD) and the possibility of using dapagliflozin at a dose of 10 mg once a day compared with placebo. The study involved 386 centers from 21 countries. A total of 4304 patients were included in the study, the average age was 61.8 years, men predominated, 2906 (67.5%) patients had an initial diagnosis of type 2 diabetes. Patients with diabetic and non-diabetic CKD were included with an estimated glomerular filtration rate (eGFR) of 25 to 75 ml/min/1.73 m2 and a urinary albumin/creatinine ratio of 200 to 5000 mg/g. Results. The primary composite endpoint (time to eGFR reduction of 50% or more compared to baseline, time to end-stage renal disease defined as eGFR15 ml/min/1.73 m2, need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death) was shown to occur in 9.2% of patients treated with dapagliflozin and in 14.5% of patients treated with placebo. Also, dapagliflozin therapy was less likely to have a secondary endpoint, such as a combination of a decrease in eGFR by 50% or more, end-stage kidney disease, or renal death. Less frequently, the dapagliflozin group experienced cardiovascular death or hospitalization for heart failure, as well as death from any cause. Conclusion. Thus, dapagliflozin demonstrated the ability, in comparison with placebo, to reduce the primary composite point and a number of secondary composite points in patients with both diabetic and non-diabetic CKD.

scholarly journals Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017121 ◽  
Author(s):  
Gowrie Balasubramaniam ◽  
Trisha Parker ◽  
David Turner ◽  
Mike Parker ◽  
Jonathan Scales ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Interleukin 1 ◽  
Scale Up ◽  
General Information ◽  
Primary Objective ◽  
Retention Rates ◽  
Acute Gout ◽  
Double Blind

IntroductionAcute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD).Methods and analysisASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies.Ethics and disseminationThe London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberEudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No.NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614–34090.

Probiotic Supplementation in Chronic Kidney Disease: A Double-blind, Randomized, Placebo-controlled Trial

2018 ◽  
Vol 28 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Natália A. Borges ◽  
Flávia L. Carmo ◽  
Milena B. Stockler-Pinto ◽  
Jessyca S. de Brito ◽  
Carla J. Dolenga ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Probiotic Supplementation ◽  
Double Blind

Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial

2020 ◽  
Author(s):  
Masanori Asakura ◽  
Shin Ito ◽  
Takahisa Yamada ◽  
Yoshihiko Saito ◽  
Kazuo Kimura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Placebo Group ◽  
Acute Heart Failure ◽  
Primary Outcome ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Early Initiation ◽  
Left Ventricular Ejection ◽  
Double Blind ◽  
Double Blind Placebo

Abstract Aims A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. Methods and results In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642–1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213–1.434). The safety profile for eplerenone was as expected. Conclusion The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

scholarly journals Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease

Circulation ◽  
2020 ◽  
Author(s):  
John J.V. McMurray ◽  
David C. Wheeler ◽  
Bergur V. Stefánsson ◽  
Niels Jongs ◽  
Douwe Postmus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Secondary Prevention ◽  
Cardiovascular Death ◽  
Composite Outcome ◽  
Primary And Secondary Prevention ◽  
History Of ◽  
End Stage

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150

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