Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Statins use for primary prevention of cardiovascular disease: A population-based digitally enabled real-world evidence cross-sectional study in primary care in Brazil.

BACKGROUND: Statins are the main strategy to reduce dyslipidemia-related cardiovascular risk. Nevertheless, there is scarce evidence on the real-world statins use in primary care settings in low-middle-income countries. OBJECTIVE: We conducted a cross-sectional retrospective study using anonymized data routinely collected by community health workers in Brazil aimed to evaluate statin use and associated factors in a primary prevention population with cardiovascular risk enhancers. METHODS: Study population consisted of adults with hypertension, diabetes, and/or dyslipidemia. The primary and secondary outcomes were the proportion of individuals self-reporting statins use on any dose and high-dose statins/high-intensity lipid-lowering therapy (LLT), respectively. RESULTS: Of the 2,133,900 adult individuals in the database, 415,766 (19.5%) were included in the study cohort. From this cohort, 89.1% had hypertension, 28.9% diabetes, and 5.5% dyslipidemia. The mean age was 61.5 (standard deviation 14.5) years, 63.4% were female, and 61.0% were of mixed-race. Only 2.6% and 0.1% of individuals self-reported the use of statins and high-dose statins/high-intensity LLT, respectively. Older age (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.88, 2.05, p < 0.001), living in the South region of Brazil (OR 4.39; 95% CI 3.97, 4.85, p < 0.001), heart failure (OR 2.60; 95% CI 2.33, 2.89, p < 0.001), chronic kidney disease (OR 1.49; 95% CI 1.35, 1.64, p < 0.001), and anti-hypertensive medications use (OR 4.38; 95% CI 4.07, 4.71, p < 0.001) were independently associated with statin use. CONCLUSION: In a real-world evidence study analyzing data routinely collected in a digitized primary care setting, we observed a very low use of statins in a primary prevention population with cardiovascular risk enhancers in Brazil. Socio-demographic factors and co-morbidities were associated with higher statins use rates.

Assessing statins use in a real-world primary care digital strategy: a cross-sectional analysis of a population-wide digital health approach.

Background: The digitization of the primary care system provides an opportunity to evaluate the current use of statins in secondary prevention populations (myocardial infarction or stroke). Methods: We conducted a cross-sectional study (ClinicalTrials.gov, NCT05285085), analysing anonymised data routinely collected by community health workers (CHW) in Brazil between May 2016 and September 2021 to assess the proportion of self-reported statins use and associated factors. Findings: From the 2,133,900 individuals on the database, 35,103 (1.6%), mean age 66.2 years (SD14.6), 49.5% (17,382/35,103) male sex, 50.5% (17,721/35,103) female sex, and 29.6% (10,381/34,975) Caucasians, had a previous myocardial infarction (MI) (n = 11,628; 33.1%) or stroke (n = 25,925; 73.9%). Approximately 50% (17,020/35,103) were from the Northeast region, 78.7% (27,605) from urban zones, and 39.4% (13,845) with social development index (SDI) >0.7. Overall, 6.7% (2346) and 0.6% (212) reported statins and high dose statins use, respectively. Age over 60 years old (OR 1.32 [95% CI 1.19-1.47), living in the Southern region (OR 4.53 [95% CI 3.66-5.60]), having a previous diagnosis of MI (OR 4.53 [95% CI 3.66-5.60]), heart failure (OR 2.29 [95% CI 1.13-1.47]), diabetes (OR 1.50 [95% CI 1.37-1.64]), dyslipidaemia (OR 2.90 [95% CI 2.55-3.29]), chronic kidney disease (OR 1.27 [95% CI 1.08-1.48]) and use of anti-hypertensives (OR 5.47 [95% CI 4.60-6.47]) were associated with statin use. Interpretation: The analysis of a real-world database from a digitized primary care system, allowed us to identify a very low use of statins in secondary prevention Brazilian patients, mostly influenced by socio-demographic factors and co-morbidities. Funding: Novartis Biociências, Brazil.