Metformin in Systemic Lupus Erythematosus: Investigating Cardiovascular Impact and Nephroprotective Effects in Lupus Nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE. METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis. RESULTS: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups. CONCLUSION: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects.

Outcomes with inpatient use of midodrine in patients with heart failure and kidney failure on maintenance dialysis.

BACKGROUND: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF. METHODS: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities. RESULTS: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality. CONCLUSION: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.

Association of mildly elevated pulmonary vascular resistance with major cardiovascular events in pulmonary hypertension and chronic kidney disease: A retrospective cohort analysis.

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance ( > 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1-year follow-up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes.

Cardiovascular outcomes of sodium-glucose Co-transporter 2 inhibitors use after myocardial infarction: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients who had acute myocardial infarction are at high risk of negative cardiac outcomes and previous SGLT2i landmark trials excluded these patients. It therefore remains unclear if SGLT2i is safe and confers beneficial cardiovascular outcomes after acute myocardial infarction. METHODS: We systematically reviewed randomized controlled trials that evaluated the outcomes of adding SGLT2i to conventional post-myocardial infarction care. Random-effects model meta-analysis via RevMan 5.4 was done on data extracted from pooled 11,204 patients. RESULTS: SGLT2i use after acute myocardial infarction was significantly associated with reduced heart failure hospitalization (OR: 0.77, 95%CI: 0.62-0.96, p=0.02), but was not associated with a reduction in all-cause mortality (OR: 1.05, 95%CI: 0.77-1.43, p=0.75), cardiac-related death (OR: 1.04, 95%CI: 0.83-1.30, p=0.76), or major adverse cardiac events (OR: 0.90, 95%CI: 0.77-1.05, p=0.18). CONCLUSION: SGLT2 inhibitor therapy after acute myocardial infarction is safe and is associated with a reduced risk of heart failure hospitalization, but not with all-cause mortality.

Impact of comorbid heart failure among hospitalized patients with sarcoidosis: A United States population-based cohort study.

Background: There is paucity of data regarding the impact of concomitant heart failure (HF) on the in-hospital outcomes among hospitalized sarcoidosis patients. We aim to investigate the factors associated with concomitant HF and its impact on in-hospital outcomes among hospitalized sarcoidosis patients. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting this study. Multivariable logistic and linear regression models were used to examine the factors associated with HF and hospital-associated outcomes among patients with sarcoidosis. Results: A total of 36,864 hospitalized patients with sarcoidosis were identified, of which 24.78 % (n = 9135/36,864) had concomitant HF. Factors associated with concomitant HF were age (aOR 1.03; 95 % CI: 1.02-1.03, p value ≤ 0.001), black race (aOR 1.74; 95 % CI: 1.47-2.05, p value ≤ 0.001), not being female (aOR 0.79; 95 % CI: 0.69-0.91, p value ≤ 0.001), and arrhythmias (aOR 2.50; 95 % CI: 2.10-2.98, p value ≤ 0.001) specifically atrial fibrillation and ventricular tachycardia. Comorbidities associated with concomitant HF in this population were hyperlipidemia, obesity, coronary artery disease, cardiac device implantation history, and chronic kidney disease stage 1-4. Concomitant HF was not an independent predictor of in-hospital mortality or length of stay (LOS). However, age (aOR 1.04; 95 % CI, 1.03-1.06; p ≤ 0.001) and arrhythmia burden (aOR 2.08; 95 % CI, 1.47-2.95; p ≤ 0.001), specifically ventricular tachycardia and fibrillation, were independently associated with in-hospital mortality among sarcoidosis patients. Conclusion: Traditional cardiovascular risk factors were associated with concomitant HF among hospitalized sarcoidosis patients. Moreover, concomitant HF among sarcoidosis patients was not significantly associated with in-hospital mortality or LOS.

Proportional troponin changes and risk for outcomes with intervention strategies in non-ST-elevation acute coronary syndrome across kidney function.

AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.

Clinical predictors and outcomes of pulmonary infarction in patients with central pulmonary embolism.

BACKGROUND: Given the heterogeneity of predisposing factors associated with pulmonary infarction (PI) and the lack of clinically relevant outcomes among patients with acute pulmonary embolism (PE) complicated by PI, further investigation is required. METHODS: Retrospective study of patients with central PE in an 11-year period. Data were stratified according to the diagnosis of PI. Multivariable logistic regression analysis was used to analyze factors associated with PI development and determine if PI was associated with severe hypoxemic respiratory failure and mechanical ventilation use. RESULTS: Of 645 patients with central PE, 24% (n = 156) had PI. After adjusting for demographics, comorbidities, and clinical features on admission, only age (OR 0.98, CI 0.96-0.99; p = 0.008) was independently associated with PI. Regarding outcomes, 35% (n = 55) had severe hypoxemic respiratory failure, and 19% (n = 29) required mechanical ventilation. After adjusting for demographics, PE severity, and right ventricular dysfunction, PI was independently associated with severe hypoxemic respiratory failure (OR 1.78; CI 1.18-2.69, p = 0.005) and mechanical ventilation (OR 1.92; CI 1.14-3.22, p = 0.013). CONCLUSIONS: Aging is a protective factor against PI. In acute central PE, subjects with PI had higher odds of developing severe hypoxemic respiratory failure and requiring mechanical ventilation.

Combination prophylactic amiodarone with beta-blockers versus beta-blockers in atrial fibrillation after cardiac surgery: A systematic-review and meta-analysis.

BACKGROUND: Guideline recommendations regarding the preferred preventive measures for postoperative atrial fibrillation (POAF) are unclear, nor have we found any review articles addressing the combination of amiodarone and beta-blockers for the prevention of POAF. OBJECTIVES: To investigate the efficacy and safety of combination beta-blockers and amiodarone in the prevention of POAF while also comparing the use of amiodarone and beta-blockers individually. METHODS: We used Pubmed as the primary resource. POAF incidence was the primary outcome of this study. The secondary outcomes were hospital length of stay (LOS), ICU LOS, treatment-related drug discontinuation (TRDD), and mortality. The random-effects model assessed all pooled outcomes with 95% confidence intervals. Statistical significance was set at p≤0.05. RESULTS: The amiodarone subgroup of POAF incidence saw a Risk Ratio (RR) of 0.81 [0.63, 1.06], p=0.12, while the combination subgroup resulted in a RR of 0.63 [0.49, 0.80], p <0.001. TRDD for the amiodarone subgroup resulted in a RR of 0.68 [0.25, 1.82], p=0.44, while the combination subgroup saw a RR of 0.84 [0.57, 1.23], p=0.36. For mortality, the amiodarone subgroup resulted in a RR of 0.97 [0.48, 1.98], p=0.93, while the combination subgroup resulted in a RR of 1.04 [0.27, 4.05], p=0.96. Both hospital and ICU LOS saw no significant difference between treatment arms for both the combination subgroup and amiodarone alone. Except for the incidence of postoperative atrial fibrillation (POAF) in the combination prophylaxis group, most of the measured outcomes did not meet the optimized information size (OIS) that was estimated. CONCLUSION: Combination prophylaxis with amiodarone and beta-blockers significantly lowered risks of POAF incidence in comparison to beta-blockers alone while also having comparative mortality and TRDD outcomes.

Focal Alveolar Hemorrhage Secondary to Hydralazine-Associated Antineutrophilic Cytoplasmic Antibody Vasculitis.

Hydralazine is rarely associated with antineutrophilic cytoplasmic antibody (ANCA) vasculitis. In the appropriate clinical scenario, such as in a patient with pulmonary, renal, or cutaneous manifestations, finding antibodies against nuclear and cytoplasmic neutrophil antigens may suggest drug-induced vasculitis after exposure to hydralazine. We present the case of an elderly man diagnosed with focal alveolar hemorrhage with elevated concentrations of anti-myeloperoxidase antibody, anti-proteinase-3 antibody, and antinuclear antibodies in the setting of prolonged hydralazine therapy. We observed a rapid clinical improvement with hydralazine discontinuation and systemic corticosteroids. We did not observe further disease activity while on mycophenolate mofetil six months later.

Clinical features and risk factors of adverse clinical outcomes in central pulmonary embolism using machine learning analysis.

BACKGROUND: In prior studies, central pulmonary embolism (PE) was associated with high clot burden and was considered an independent predictor for thrombolysis. Further information about predictors of adverse outcomes in these patients is needed for better risk stratification. The objective is to describe independent predictors of adverse clinical outcomes in patients with central PE. METHODS: Large retrospective, observational, and single-center study of hospitalized patients with central PE. Data were gathered on demographics, comorbidities, clinical features on admission, imaging, treatments, and outcomes. Multivariable standard and Least Absolute Shrinkage and Selection Operator (LASSO) machine learning logistic regressions and sensitivity analyses were used to analyze factors associated with a composite of adverse clinical outcomes, including vasopressor use, mechanical ventilation, and inpatient mortality. RESULTS: A total of 654 patients had central PE. The mean age was 63.1 years, 59% were women, and 82% were African American. The composite adverse outcome was observed in 18% (n = 115) of patients. Serum creatinine elevation (odds ratio [OR] = 1.37, 95% CI = 1.20-1.57; p = 0.0001), white blood cell (WBC) count elevation (OR = 1.10, 95% CI = 1.05-1.15; p < 0.001), higher simplified pulmonary embolism severity index (sPESI) score (OR = 1.47, 95% CI = 1.18-1.84; p = 0.001), serum troponin elevation (OR = 1.26, 95% CI 1.02-1.56; p = 0.03), and respiratory rate increase (OR = 1.03, 95% CI = 1.0-1.05; p = 0.02) were independent predictors of adverse clinical outcomes. CONCLUSION: Among patients with central PE, higher sPESI score, WBC count elevation, serum creatinine elevation, serum troponin elevation, and respiratory rate increase were independent predictors of adverse clinical outcomes. Right ventricular dysfunction on imaging and saddle PE location did not predict adverse outcomes.

Clinical characteristics and treatment of patients with central pulmonary embolism and right heart thrombus.

INTRODUCTION: Right heart thrombus (RHT), also known as clot in transit, is an uncommon finding in pulmonary embolism (PE) that is associated with increased inpatient mortality. To date, there is no consensus on the management of RHT. Therefore, we aim to describe the clinical features, treatments, and outcomes of patients with simultaneous RHT and PE. METHODS: This is a retrospective, cross-sectional, and single-center study of hospitalized patients with central PE who had RHT visualized on transthoracic echocardiography (TTE) from January 2012 to May 2022. We use descriptive statistics to describe their clinical features, treatments, and outcomes, including mechanical ventilation, major bleeding, inpatient mortality, length of hospital stay, and recurrent PE on follow-up. RESULTS: Of 433 patients with central PE who underwent TTE, nine patients (2%) had RHT. The median age was 63 years (range 29-87), most were African American (6/9), and females (5/9). All patients had evidence of RV dysfunction and received therapeutic anticoagulation. Eight patients received RHT-directed interventions, including systemic thrombolysis (2/9), catheter-directed suction embolectomy (4/9), and surgical embolectomy (2/9). Regarding outcomes, 4/9 patients were hemodynamically unstable, 8/9 were hypoxemic, and 2/9 were mechanically ventilated. The median length of hospital stay was six days (range 1-16). One patient died during hospital admission, and two patients had recurrent PE. CONCLUSION: We described the different therapeutic approaches and outcomes of patients with RHT treated in our institution. Our study adds valuable information to the literature, as there is no consensus on the treatment of RHT. HIGHLIGHTS: Right heart thrombus (RHT) was a rare finding in central pulmonary embolism. Most patients with RHT had evidence of RV dysfunction and pulmonary hypertension. Most patients received RHT-directed therapies in addition to therapeutic anticoagulation.

"Renalism" with Renin Angiotensin Aldosterone System Inhibitor Use in Patients Enrolled in Trials for Heart Failure with Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD). METHODS: We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m2) were recorded per year. The proportion of trials with advanced CKD was logtransformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson's correlation and univariate linear regression. RESULTS: A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year. CONCLUSION: In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased.

Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in hospitalized patients with COVID-19: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Our prior analysis demonstrated no significant difference in risk of mortality or disease progression among patients with COVID-19. With the availability of findings from randomized controlled trials (RCTs), we provide an updated review of RCTs which explored the outcomes among hospitalized patients with COVID-19 treated with Angiotensin Converting Enzyme inhibitor (ACEis)/Angiotensin Receptor Blockers (ARBs) versus control. RESEARCH DESIGN AND METHODS: This systematic review and meta-analysis covers RCTs exploring mortality, intensive care unit admission, and mechanical ventilation outcomes among hospitalized COVID-19 patients treated with ACEi/ARBs. RESULTS: Ten studies were included in this meta-analysis. For mortality with ACEi/ARB utilization among hospitalized COVID-19 patients, the pooled risk ratio (RR) was 0.97 (95% CI 0.64-1.47, p = 0.89) with heterogeneity of 26%. Further, the pooled RR for ACEi/ARB use on ICU admission and mechanical ventilation were 0.55 (0.55-1.08, p = 0.13) with a heterogeneity of 0% and 1.02 (0.78-1.32, p = 0.91) with a heterogeneity of 0%, respectively. CONCLUSION: Among hospitalized patients with COVID-19, the use of ACEi/ARB was not associated with increased risk of mortality, ICU admission, or mechanical ventilation compared to control. These findings support continuation of ACEi/ARB for whom baseline clinical indications for these agents exist.

Representation of Chronic Kidney Disease in Randomized Controlled Trials Among Patients With Heart failure With Reduced Ejection Fraction: A Systematic Review.

Patients with advanced chronic kidney disease (CKD) have largely been excluded from randomized control trials (RCTs) in heart failure (HF). This creates a paucity of high quality evidence for guideline directed medical therapy (GDMT), particularly in patients with heart failure with reduced ejection fraction (HFrEF) and CKD. This is a systematic review looking at the patterns and rates of inclusion of CKD in RCTs among patients with HFrEF. The search included RCTs from January 2010 to December 2020. A heat map was constructed to reflect the stages of CKD stages. The percentage of studies that included advanced CKD (stages IV-V) was recorded and log transformed, and then fitted into a time regression model. A P value of <0.05 was considered statistically significant. Out of the 3052 screened, 706 studies were included in the analysis. Only 61% of the RCTs reported at least some information on kidney function. There was a trend of increase in percentage of studies that included CKD stages IV-V from years 2010 to 2020. This was confirmed with a statistically significant linear trend P = 0.02 while the percentage of studies that included dialysis and kidney transplant recipients remained consistently low. There is a paucity of high-quality evidence for GDMT in the HFrEF population with CKD, particularly in those with advanced non-dialytic CKD, those on maintenance dialysis and kidney transplant recipients. There is a pressing need for wider inclusion of patients with advanced CKD in RCTs of GDMT in HFrEF.

Adjunctive Dexmedetomidine in Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis of Retrospective Cohort Studies and Randomized Controlled Trials.

OBJECTIVE: To investigate whether dexmedetomidine (DEX), as adjunctive therapy to benzodiazepine (BZD), is superior to BZD alone in critically ill patients with alcohol withdrawal syndrome (AWS). DATA SOURCES: PubMed Central, Cochrane CENTRAL, ClinicalTrials.gov and Google Scholar were used as search databases. Specific keywords and MeSH terms were "dexmedetomidine," "benzodiazepine," and "alcohol withdrawal syndrome." The last search was on September 16, 2022. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) and nonrandomized/cohort studies exploring the use of DEX in the management of AWS were included. A total of 12 studies were included in the systematic review and 7 in the meta-analysis. DATA SYNTHESIS: The intensive care unit length of stay (ICU LOS) was found to have a mean difference (MD) of 48.06 [37.48, 58.64], P = <0.001 for the cohort subgroup, significantly favoring the DEX arm, but, in contrast, pooled RCT data showed a result of -20.07 [-36.86, -3.28], P = 0.02, a shorter ICU LOS for the DEX arm. Bradycardia and hypotension incidence significantly favored the BZD arm in both subgroups. This study compares the effectiveness of adjunctive DEX in clinical practice and aims to help providers in critical decision-making by compiling and analyzing the best current available evidence of its use in AWS. CONCLUSIONS: Based on low to very low level of evidence, adjunctive DEX showed no significant difference for ICU LOS when compared with BZD alone. Pooled randomized trials potentially show a benefit but are similarly limited by their low quality of evidence.

Angiotensin Receptor Neprilysin Inhibitor Use and Blood Pressure Lowering in Patients With Heart Failure With Reduced Ejection Fraction Across the Spectrum of Kidney Function: An Analysis of the Veterans Administrative Health System.

BACKGROUND: A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function. METHODS: Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates. RESULTS: There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P < 0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P < 0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73m2 or continuously across a wide range of eGFR (Pinteraction > 0.10 for both). CONCLUSION: The use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease.

Non-steroidal mineralocorticoid receptor antagonists and cardiorenal outcomes in chronic kidney disease.

The burden of adverse cardiorenal outcomes among patients with the trifecta of diabetes, heart failure (HF) and chronic kidney disease (CKD) remains high. Steroidal mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in patients with HF, however, there is significant underutilization of these agents, especially in patients with advanced CKD. Non-steroidal MRAs are an emerging therapeutic option for patients with diabetic kidney disease and are now guideline-supported in this population. Non-steroidal MRAs have a unique pharmacological profile distinct from their steroidal counterparts that retains the class-specific cardiorenal benefits but may help mitigate adverse effects, especially hyperkalaemia, in patients with CKD. In this review we summarize the current evidence on the use of non-steroidal MRAs for improving cardiorenal outcomes in patients with CKD and diabetes, as well as for combination use alongside other foundational medical therapies used in HF and CKD.