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  • Oxford University Press (OUP)  (4)
  • Sanchez, Juan Jose Garcia  (4)
  • 1
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. 5 ( 2023-05-04), p. 1260-1270
    Abstract: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1–3 and less in stages 4–5 than placebo [0.65 (95% CrI 0.41, 0.90) and –0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 2
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
    Abstract: Chronic kidney disease (CKD) and its associated complications constitute a major challenge for healthcare systems worldwide. Albuminuria, measured as albumin-to-creatinine ratio (uACR), is a critical marker of glomerular injury and endothelial dysfunction. Elevated uACR is an independent predictor of CKD progression and cardio-renal mortality [1,2]. However, there is a paucity of data translating the burden of CKD at the population level according to uACR categories, in order to promote evidence-based policies. This study aims to assess the future epidemiological and financial burden of CKD using the Inside CKD microsimulation [3] . Specifically, we report CKD population level projections for cardio-renal complications, progression to end stage kidney disease (ESKD), and death due to any cause according to uACR categories. Method The Inside CKD microsimulation was used to simulate virtual individuals from 28 countries and regions. Individuals were assigned baseline characteristics such as age or sex based on national statistics, and estimated glomerular filtration rate (eGFR), uACR, CKD stage, and cardio-renal complications based on data from national health surveys or epidemiological studies. The following cardio-renal complications were projected between 2022 and 2027 according to uACR categories (normo-, micro-, macro-albuminuria): myocardial infarction (MI), stroke, heart failure (HF), CKD transition from stage 3 to 4 and from 4 to 5 (defined as a change in either eGFR or uACR category), and death due to any cause. Results Projected estimates for the total CKD population (all stages) with macro-albuminuria varied by country and region for 2023 (mean = 9.8%, range = 1.6% – 40.2%). The lowest percentages of macro-albuminuria ( & lt; 5%) were in Romania, Belgium, and the UK, compared to the highest (≥ 27%) in Brazil, Philippines and Mexico. Macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per person basis, but according to these estimates only a small proportion of the population have macro-albuminuria. Hence, the predominant CKD population with normo- or micro-albuminuria would be expected to account for most of the clinical burden. Accordingly, most of the cardio-renal incident events projected to occur by 2027 will be in the population with normo- or micro-albuminuria in all countries and regions (Figure 1): MI (97.9%), stroke (96.5%), HF (98.0%), the transition from CKD stage 3 to 4 (94.9%) and from stage 4 to 5 (97.5%), and death due to any cause (95.6%) (percentages represent mean and included the combined normo- and micro-albuminuria populations). Conclusion Although, macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per patient basis, the total CKD population should be considered with regards to the clinical burden in absolute terms. The Inside CKD microsimulation supports early intervention in the total CKD population, including individuals with normo- or micro-albuminuria, to reduce cardio-renal outcomes, delay progression to ESKD, and therefore the requirement for costly interventions, including heart related hospitalisations, transplantation and dialysis.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
    Location Call Number Limitation Availability
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  • 3
    In: Clinical Kidney Journal, Oxford University Press (OUP)
    Abstract: The DAPA-CKD trial enrolled patients with estimated glomerular filtration rate 25–75 ml/min/1.73m2 and urine albumin-to-creatinine ratio & gt;200 mg/g. The DECLARE-TIMI 58 trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy, and Japan. Methods We adapted a published Markov model based on the DAPA-CKD trial only to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon. Results Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45–0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy, and Japan (${\$}$10 676/QALY, ${\$}$14 479/QALY; ${\$}$7771/QALY, and ${\$}$13 723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status. Conclusion Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2656786-6
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  • 4
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), ( 2024-05-10)
    Abstract: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. Methods Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. Results In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0–31.5; standard therapy: 18.5, 95%CI: 14.7–23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9–38.3; standard therapy: 29.6, 95%CI: 25.5–34.7). Conclusion Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1465709-0
    Location Call Number Limitation Availability
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