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Patients with heart failure (HF), particularly those with impaired renal function receiving renin–angiotensin–aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow‐up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one‐quarter to two‐fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55–93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow‐up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE‐HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Patients with heart failure (HF), particularly those with impaired renal function receiving renin–angiotensin–aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow‐up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one‐quarter to two‐fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55–93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow‐up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE‐HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes.

INTRODUCTION: Hyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK. METHODS: Adults (≥ 18 years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes. RESULTS: A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0 years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up  = 8.1 months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p

Background: Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes, with the incidence rate increasing yearly, which is the leading cause of chronic kidney disease (CKD) and endstage kidney disease. Abelmoschus Manihot capsule, as a proprietary Chinese patent medicine, is widely used for treating CKD in China. Currently, the combination of Abelmoschus Manihot (AM) capsule and renin-angiotensinaldosterone system inhibitor (RASI) has gained popularity as a treatment option for DKD, with more and more randomized control trials (RCTs) in progress. However, the high-quality clinical evidence supporting its application in DKD is still insufficient. Aim of the study: To comprehensively and systematically evaluate the efficacy and safety of AM capsule combined with RASI in the treatment of DKD. Materials and methods: English and Chinese databases such as Pubmed, Cochrane Library, Embase, CNKI, SinoMed, WF, and VIP were searched to collect the RCTs of AM capsule in treatment of DKD. Then Two investigators independently reviewed and extracted data from the RCTs which met the inclusion criteria. The quality of the data was assessed using the Cochrane risk of bias assessment tool, and meta-analysis was performed using RevMan 5.4 software. Results: 32 RCTs with a total of 2,881 DKD patients (1,442 in the treatment group and 1,439 in the control group) were included. The study results showed that AM capsule combined with RASI could be more effective in decreasing 24h-UTP [MD = -442.05, 95% CI (-609.72, -274.38), p < 0.00001], UAER [MD = -30.53, 95% CI (-39.10, -21.96), p < 0.00001], UACR [MD = -157.93, 95% CI (-288.60, -27.25), p < 0.00001], Scr [MD = -6.80, 95% CI (-9.85, -3.74), p < 0.0001], and BUN [MD = -0.59, 95% CI (-1.07, -0.12), p = 0.01], compared to using RASI alone. According to the subgroup analyses, the combination of AM and ARB seems to be more effective in reducing UAER than the combination of ACEI, and the addition of AM may achieve a more significant clinical effect on decreasing Scr for DKD patients with 24h-UTP>2 g or Scr>110--133 μmol/L and >133 μmol/L. Furthermore, no additional adverse reactions were observed in the combination group [OR = 1.06; 95%CI: (0.66, 1.69), p = 0.82]. Conclusion: Combining AM with RASI may be a superior strategy for DKD treatment compared to RASI monotherapy. However, due to significant heterogeneity, the results should be interpreted with great caution, and more high-quality RCTs with multi-centers, different stages of DKD, large sample sizes, and long follow-up periods are still needed to improve the evidence quality of AM for DKD in the future. [ABSTRACT FROM AUTHOR]

Background We evaluated the potential benefits of renin‐angiotensin‐aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. Methods and Results A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6‐month on support were studied. RAASi status after 6‐month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6‐month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6‐month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6‐month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure

Background Previous data suggest that using renin-angiotensin-aldosterone system inhibitors (RAASIs) improves survival in patients with cardiovascular diseases. We sought to investigate the association of different patterns of use of RAASIs on perioperative and 1-year outcomes following carotid revascularization. Methods and Results We investigated patients undergoing carotid revascularization, either with carotid endarterectomy or transfemoral carotid artery stenting, in the VQI (Vascular Quality Initiative) VISION (Vascular Implant Surveillance and Interventional Outcomes Network) data set between 2003 and 2018. We divided our cohort into 3 groups: (1) no history of RAASI intake, (2) preoperative intake only, and (3) continuous pre- and postoperative intake. The final cohort included 73 174 patients; 44.4% had no intake, 50% had continuous intake, and 5.6% had only preoperative intake. Compared with continuous intake, preoperative and no intake were associated with higher odds of postoperative stroke (odds ratio [OR], 1.7 [95% CI, 1.5-1.9]; P

Introduction: There is increasing awareness of non-adherence to renin-angiotensin- aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD). This study aimed to evaluate the incidence of hyperkalemic adult CKD patients who were prescribed RAASi and to determine variations in pharmacological interventions to uncover reasons for non-adherence to RAASi treatment. Methods: The incidence of hyperkalemia and non-adherence to RAASi [angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARBs)] in CKD patients was examined among 471 patients over the age of 18 years who had estimated-glomerular filtration rate (e-GFR) measurements and were diagnosed with CKD between stages 1 and 5. Hyperkalemia was defined as serum potassium (K+) ≥5 mmol/L. The number of hyperkalemic patients not reaching the target dose, hyperkalemia as a reason for not reaching the target dose, patients receiving sodium polystyrene sulfonate patients discontinuing ACEi/ARBs, having a decreased dose of ACEi/ARBs, or treated with the addition or increasing dose of diuretics were compared between the hyperkalemia groups. Results: Hyperkalemia was detected in 29.1% of the patients (n=137), being mild in 21.7%, moderate in 6.2%, and severe in 1.3%. The main finding was that the frequency of patients not reaching the target dose of ACEi/ARBs treatment due to hyperkalemia, hypotension, or e-GFR increase higher than 30% was dramatically higher among patients having moderate/severe hyperkalemia (p

Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin–angiotensin–aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima–media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients’ quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin–angiotensin–aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN). Methods: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine–Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding. Results: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762–0.929). The result was consistent in various sensitivity analyses and important subgroup analyses. Conclusions: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: There is increasing awareness of non-adherence to renin-angiotensin- aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD). This study aimed to evaluate the incidence of hyperkalemic adult CKD patients who were prescribed RAASi and to determine variations in pharmacological interventions to uncover reasons for non-adherence to RAASi treatment. Methods: The incidence of hyperkalemia and non-adherence to RAASi [angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARBs)] in CKD patients was examined among 471 patients over the age of 18 years who had estimated-glomerular filtration rate (e-GFR) measurements and were diagnosed with CKD between stages 1 and 5. Hyperkalemia was defined as serum potassium (K+) ≥5 mmol/L. The number of hyperkalemic patients not reaching the target dose, hyperkalemia as a reason for not reaching the target dose, patients receiving sodium polystyrene sulfonate patients discontinuing ACEi/ARBs, having a decreased dose of ACEi/ARBs, or treated with the addition or increasing dose of diuretics were compared between the hyperkalemia groups. Results: Hyperkalemia was detected in 29.1% of the patients (n=137), being mild in 21.7%, moderate in 6.2%, and severe in 1.3%. The main finding was that the frequency of patients not reaching the target dose of ACEi/ARBs treatment due to hyperkalemia, hypotension, or e-GFR increase higher than 30% was dramatically higher among patients having moderate/severe hyperkalemia (p<0.0001). In 12.41% of hyperkalemic patients, hyperkalemia was cited as the cause for not achieving the target dosage of ACEi/ARB therapy. 25.71% of these patients discontinued ACEi/ARBS treatment, 14.29% had decreased dose of this treatment, and 11.43% had increased dose of diuretics or newly prescribed diuretics. However, none of the patients with mild hyperkalemia experienced these events during treatment. Conclusion: These findings suggest that serum K+ concentration may be related to major adverse clinical outcomes and affect the type of pharmacological intervention in CKD, resulting in ACEi-ARB discontinuation and halting to reach the target dose. [ABSTRACT FROM AUTHOR]

Introduction Heart failure (HF) is still a major cause of morbidity and mortality all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan (S/V) compared to angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in patients with HF. Material and methods We systematically searched for randomised controlled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF in August 2021. Primary outcomes were HF hospitalisations and cardiovascular (CV) mortality; secondary outcomes included all-cause mortality, biomarkers, and renal function. Results We selected 11 RCTs (n = 18766) with 2-48 months follow-up. Five RCTs had ACEIs as control, 5 RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Compared to ACEI or ARB, S/V reduced HF hospitalisations by 20% (HR = 0.80, 95% CI: 0.68–0.94; 3 RCTs; I 2 = 65%; high CoE), CV mortality by 14% (HR = 0.86, 95% CI: 0.73–1.01; 2 RCTs; I 2 = 57%; high CoE), and all-cause mortality by 11% (HR = 0.89, 95% CI: 0.78–1.00; 3 RCTs; I 2 = 36%; high CoE). S/V reduced NTproBNP (SMD = –0.34, 95% CI: –0.52 to –0.16; 3 RCTs; I 2 = 62%) and hs-TNT (ratio of differences = 0.84, 95% CI: 0.79–0.88; 2 RCTs; I 2 = 0%), and caused a decline in renal function by 33% (HR = 0.67, 95% CI: 0.39–1.14; 2 RCTs; I 2 = 78%; high CoE). S/V increased hypotension (RR = 1.69, 95% CI: 1.33–2.15; 9 RCTs; I 2 = 65%; high CoE). Hyperkalaemia and angioedema events were similar. Effects were in the same direction when stratified by type of control (ACEI vs. ARB). Conclusions Sacubitril/valsartan had better clinical, intermediate, and renal outcomes in HF in comparison to ACEI or ARB. There was no difference in angioedema and hyperkalaemia events, but there were more hypotension events.

Abstract Background Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte‐mediated antitumor activity. Methods We conducted a retrospective cohort study to investigate the impact of PPAR‐γ‐activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. Results A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non‐PPAR‐γ‐ARB users (n = 102), PPAR‐γ‐ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0—not reached] vs. 18.6 [IQR, 6.1–38.6] months) and progression‐free survival (17.3 [IQR, 5.1—not reached] vs. 8.2 [IQR, 2.4–18.6] months). In Cox regression analysis, the use of PPAR‐γ‐activating ARBs had an approximately 50% reduction in all‐cause mortality and disease progression. Patients who received PPAR‐γ‐activating ARBs also had higher clinical benefit rates than non‐PPAR‐γ‐ARB users (82% vs. 61%, p = 0.005). Conclusion The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs.

Abstract Aims Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real‐world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients. Methods and results A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level 5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0–5.0 mmol/L and

Background Heart failure with improved ejection fraction (EF) is increasingly recognized as a sizable and distinct entity. While the features associated with improvedEF have been explored and new guidelines have emerged, factors associated with sustaining an improved EF over time have not been defined. We aimed to assess factors associated with maintenance of an improved EF in a large real‐world patient cohort. Methods and Results A total of 7070 participants with heart failure with improved EF and a subsequent echocardiogram performed after at least 9 months of follow‐up were included in a retrospective cohort study conducted at the Cleveland Clinic in Cleveland, Ohio. Multiple logistic regression models, adjusted for demographics, comorbidities, and medications were built to identify characteristics and therapeutic interventions associated with maintaining an improved EF. Mean age (SD) was 64.9 (13.8) years, 62.7% were men, and 75.1% were White participants. White race and the use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor–neprilysin inhibitors were associated with maintaining the EF at least 9 months after EF improvement. In contrast, male sex or having atrial fibrillation/flutter, coronary artery disease, history of myocardial infarction, presence of an implanted cardioverter‐defibrillator, and use of loop diuretics were associated with a decline in EF after previously documented improvement. Conclusions Continued use of renin–angiotensin–aldosterone system inhibitors was associated with maintaining the EF beyond the initial improvement phase.

Introduction: Guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is rarely achieved in clinical settings, often due to hyperkalaemia. We assessed the potassium binder, patiromer, on continuation of RAASi therapy in hyperkalaemic patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in the AMETHYST-DN trial, propensity score-matched to a real-world cohort not receiving patiromer (Salford Kidney Study). Methods: The phase 2, open-label AMETHYST-DN trial (NCT01371747) randomized 304 adults with CKD on RAASi, T2DM, hyperkalaemia (serum potassium [sK+] >5.0 mEq/L), and hypertension to receive patiromer, 8.4–33.6 g/day for 12 months. Patients underwent propensity score matching for systolic blood pressure (BP), heart failure status, and estimated glomerular filtration rate (eGFR), with 321 patients with CKD, T2DM, hyperkalaemia, and on RAASi from a prospective CKD cohort (Salford Kidney Study). Changes in RAASi utilization, sK+, BP, proteinuria, and eGFR during 12-month follow-up were assessed by Mann-Whitney U or χ2 tests. Results: Matching produced 135:135 patients with no significant differences in age, sex, systolic BP, sK+, eGFR, or heart failure status, although differences in diastolic BP remained (p < 0.001). After 12 months, 100% of AMETHYST-DN patients receiving patiromer remained on RAASi therapy, whereas 38.5% of the Salford Kidney Cohort discontinued RAASi (p < 0.001); hyperkalaemia contributed in 16% of patients (42% of RAASi discontinuations). Significantly greater reductions in sK+ and BP, but not proteinuria or eGFR, were observed in AMETHYST-DN, compared with Salford Kidney Study patients (p < 0.05). Conclusions: These results demonstrate the benefit of patiromer for sK+ management to enable RAASi use while revealing beneficial effects on BP. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract (CAKUT) can be associated with proteinuria, possibly leading to a decline in kidney function. The aim of this review is to evaluate evidence on the efficacy of renin-angiotensin-aldosterone system inhibitors (RAASi) in children affected by CAKUT with proteinuria or chronic kidney disease (CKD). We conducted a bibliographic search between 1 December 2022 and 20 February 2023, including randomized controlled trials, case-control studies, observational studies, meta-analyses, and systematic reviews dealing with the efficacy of RAASi in reducing proteinuria and slowing the decline of kidney function in children. RAASi are effective in reducing proteinuria and slowing CKD progression in many renal conditions; however, the efficacy of these drugs in patients affected by CAKUT with proteinuria is still unknown. While waiting for more evidence, when facing a child with CAKUT with isolated proteinuria or with proteinuria and CKD, a 6–12-month trial with RAASi with gradual increase to the maximal tolerated dose should be considered. If no improvement of proteinuria is obtained, the RAASi should be discontinued. [ABSTRACT FROM AUTHOR]

Simple Summary: The involvement of the renin-angiotensin pathway in both the regulation of the cardiovascular system and in tumorigenesis raises the question of the prognostic impact of renin-angiotensin system blockers (RABs) in cancer patients experiencing life-threatening complications. The aim of our retrospective study was to assess this impact in solid tumor patients requiring unplanned ICU admission over a 14-year period. Among 1845 patients mainly diagnosed with gastrointestinal and lung cancers, 414 (22.4%) were treated with RABs: 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). ARBs use and ACEis use were both associated with improved in-ICU survival, whereas only ARBs use was associated with improved one-year survival. Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59–75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40–0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32–0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4–0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients. [ABSTRACT FROM AUTHOR]

Background: Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice. Methods: Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0. Results: A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75-0.96; P = 0.009) for OS and 0.91 (95%CI, 0.76-1.09; P = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; P = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; P = 0.005) on OS. Conclusion: Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is still a major cause of morbidity and mortality all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan (S/V) compared to angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in patients with HF. Material and methods: We systematically searched for randomised controlled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF in August 2021. Primary outcomes were HF hospitalisations and cardiovascular (CV) mortality; secondary outcomes included all-cause mortality, biomarkers, and renal function. Results: We selected 11 RCTs (n = 18766) with 2-48 months follow-up. Five RCTs had ACEIs as control, 5 RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Compared to ACEI or ARB, S/V reduced HF hospitalisations by 20% (HR = 0.80, 95% CI: 0.68-0.94; 3 RCTs; I² = 65%; high CoE), CV mortality by 14% (HR = 0.86, 95% CI: 0.73-1.01; 2 RCTs; I² = 57%; high CoE), and all-cause mortality by 11% (HR = 0.89, 95% CI: 0.78-1.00; 3 RCTs; I² = 36%; high CoE). S/V reduced NTproBNP (SMD = -0.34, 95% CI: -0.52 to -0.16; 3 RCTs; I² = 62%) and hs-TNT (ratio of differences = 0.84, 95% CI: 0.79-0.88; 2 RCTs; I² = 0%), and caused a decline in renal function by 33% (HR = 0.67, 95% CI: 0.39-1.14; 2 RCTs; I² = 78%; high CoE). S/V increased hypotension (RR = 1.69, 95% CI: 1.33-2.15; 9 RCTs; I² = 65%; high CoE). Hyperkalaemia and angioedema events were similar. Effects were in the same direction when stratified by type of control (ACEI vs. ARB). Conclusions: Sacubitril/valsartan had better clinical, intermediate, and renal outcomes in HF in comparison to ACEI or ARB. There was no difference in angioedema and hyperkalaemia events, but there were more hypotension events. [ABSTRACT FROM AUTHOR]

Background: Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte‐mediated antitumor activity. Methods: We conducted a retrospective cohort study to investigate the impact of PPAR‐γ‐activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. Results: A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non‐PPAR‐γ‐ARB users (n = 102), PPAR‐γ‐ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0—not reached] vs. 18.6 [IQR, 6.1–38.6] months) and progression‐free survival (17.3 [IQR, 5.1—not reached] vs. 8.2 [IQR, 2.4–18.6] months). In Cox regression analysis, the use of PPAR‐γ‐activating ARBs had an approximately 50% reduction in all‐cause mortality and disease progression. Patients who received PPAR‐γ‐activating ARBs also had higher clinical benefit rates than non‐PPAR‐γ‐ARB users (82% vs. 61%, p = 0.005). Conclusion: The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs. [ABSTRACT FROM AUTHOR]

Aims: Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real‐world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients. Methods and results: A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level <4.0, 4.0 to 5.0 or >5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0–5.0 mmol/L and <4.0 mmol/L (7.7% vs. 9.5% vs. 13.6% respectively, P = 0.0078). In the multivariable regression analyses, patients with hyperkalaemia were significantly less likely to receive ≥100% of the target dose compared with patients with serum potassium 4.0–5.0 mmol/L (OR 0.38, 95% CI 0.15–0.97, P = 0.044). Additionally, a one unit increase in serum potassium was significantly associated with a lower odds of receiving ≥100% of the target dose (OR 0.69, 95% CI 0.49–0.98, P = 0.036). Conclusions: In this large registry of real‐world chronic HF patients, both an increase in serum potassium and hyperkalaemia were associated with a lower odds of receiving the guideline‐recommended MRA dose. [ABSTRACT FROM AUTHOR]

Melva Louisa,1 Daniel Cahyadi,2 Dina Nilasari,3,4 Vivian Soetikno1 1Department of Pharmacology and Therapeutics, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 2Master Program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 3Department of Clinical Research, Siloam Hospitals, Jakarta, Indonesia; 4Faculty of Medicine, University of Hasanuddin, Makassar, South Sulawesi, IndonesiaCorrespondence: Melva Louisa, Department of Pharmacology and Therapeutics Faculty of Medicine Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta Pusat, Jakarta, Indonesia, Tel +62-21-319 30481, Email melva.louisa@gmail.comPurpose: This study aimed to investigate the correlation of plasma soluble angiotensin-converting enzyme 2, sACE2, and several inflammatory markers in COVID-19 patients requiring hospitalization with hypertension. Additionally, we analyzed the effects of renin-angiotensin-aldosterone-system, RAAS, inhibitors on the levels of sACE2 and inflammatory marker levels in patients with COVID-19.Patients and Methods: This cross-sectional study involved patients with COVID-19 who required hospitalization on a stable dose of antihypertensive drugs. The study included three hospitals in Jakarta and Tangerang, Indonesia, between December 2020 and June 2021. We classified eligible subjects into two groups: patients with COVID-19 treated with antihypertensive RAAS inhibitors or non-RAAS inhibitors.Results: We found no correlation between sACE2 and all the inflammatory and coagulation markers studied (high-sensitivity C-reactive protein, IL-6, IL-10, IL6/IL10, tumor necrosis factor-α, neutrophil-to-lymphocyte ratio, and D-dimer) in COVID-19 patients with hypertension. Further analysis showed lower sACE2 concentrations and IL-6/IL-10 ratio in patients treated with RAAS inhibitors vs those treated with non-RAAS inhibitors.Conclusion: We found no correlation between ACE2 and inflammatory markers. Using RAAS inhibitors resulted in a lower sACE2 and IL-6/IL-10 ratio. The type of antihypertensive treatments has a neutral effect on disease severity and outcome in COVID-19 patients with hypertension. However, to firmly-established these effects, our findings should be confirmed in a much larger population.Keywords: antihypertensive drugs, cytokines, interleukins, neutrophil-to-lymphocyte ratio, renin-angiotensin-aldosterone system inhibitors

Objective To investigate the efficacy and safety of hydroxychloroquine (HCQ) versus spironolactone in patients with IgA nephropathy based on sufficient renin-angiotensin-aldosterone system inhibitors (RAASi) treatment. Methods A prospective, non-randomized study was carried out on 172 patients with primary IgA nephropathy admitted in our department from April 2019 to March 2021. They were 56 males and 116 females, at an average age of 37.5±10.7 years. They were divided into HCQ group (n=104) and double RAASi group (n=68) and were followed up for 6 months. The decreasing rate of urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were compared between the 2 groups during follow-up, and subgroup analysis was conducted to explore the effects of corticosteroids or immunosuppressants on the outcomes. Results Compared with the dual RAASi group, the patients in the HCQ group had worse baseline renal function, lower eGFR and larger proportion of Lee's grades Ⅲ~Ⅳ (P < 0.05). At the 6th month of follow-up, the decreasing rate of UPCR was comparable between the 2 groups (-54.7% vs -52.0%, P=0.551), but the decreasing rate of eGFR was significantly lower in the HCQ group than that in the dual RAASi group (-3.3% vs -11.5%, P < 0.001). In addition, subgroup analysis found that there was no significant difference between HCQ and spironolactone in reducing urine protein, but for those who did not use corticosteroids or immunosuppressants before and after enrollment, those who did not use corticosteroids or immunosuppressants before enrollment but added them after enrollment, and those who used corticosteroids or immunosuppressants before and after enrollment, the HCQ group had a significantly lower eGFR decline rate at 6 months of follow-up than the dual RAAS group (P < 0.05). Moreover, no serious adverse events (SAEs) were observed in either group during the course of the study. Conclusion On the basis of sufficient RAASi treatment, HCQ and spironolactone have similar effects in controlling urine protein level in patients with IgA nephropathy whose urine protein does not reach the target level, and there are no serious adverse events. But HCQ has a significantly better renal protective effect of eGFR than spironolactone.

Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin–angiotensin–aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima–media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3–5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73–17,276). The median follow-up was 38 months (range 24–58). The overall median of both primary and secondary outcomes was 0 (range 0–117 and range 0–55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1–117) and 7.5 (range: 1–55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1–117) and 22 (range 1–80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD. [ABSTRACT FROM AUTHOR]

Background: Whether to continue renin–angiotensin–aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk–benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode. The incidences of the clinical outcomes of patients with RAASi (all ACEi/ARB/MRA) or MRA-only cessation (vs. non-cessation) were compared via propensity score-matched patients. A cubic spline regression analysis assessed the hazard of death resulting from treatment cessation vs. no cessation at each potassium level. Results: A total of 5059 hyperkalemic HF patients were identified; most received low to moderate doses of ACEis and ARBs (86.9% and 71.5%, respectively) and low doses of MRAs (76.2%). The RAASi and MRA cessation rates were 34.7% and 52.8% at 1 year post-diagnosis, while the dose reduction rates were 8.4% and 6.5%, respectively. During the mean follow-up of 2.8 years, patients who ceased RAASi or MRA therapies were at higher risk for adverse outcomes; cubic spline analysis found that serum potassium levels of <5.9 and <5.7 mmol/L conferred an increased mortality risk for RAASi and MRA cessation, respectively. Conclusions: Treatment cessation/dose reduction of RAASis are common among HF patients. The risks of RAASi/MRA cessation may outweigh the benefits in patients with mild to moderate hyperkalemia. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.Design: Retrospective observational study.Setting: Multicenter, international COVID-19 registry.Subjects: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.Interventions: None.Measurements and Main Results: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001).Conclusions: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

Drug-induced nephrotoxicity is the third most common cause of acute kidney injury (AKI). The aim of the study was to analyse and summarise data on the factors and mechanisms responsible for increased risk of drug-induced AKI, to analyse potential methods of its prevention and treatment. At present, the following phenotypes of drug-induced AKI are distinguished: acute vascular disease, acute glomerular disease, acute tubular injury / necrosis, and acute interstitial nephritis. It was discovered that most often these complications occur following the use of antimicrobial drugs, renin-angiotensin-aldosterone system inhibitors, non-steroidal anti-inflammatory drugs, and anticancer drugs, including targeted therapy. Risk factors for drug-induced AKI include age >65, female gender, low body weight, pre-existing chronic kidney disease, hypovolemia, hypoalbuminemia, acute and chronic heart failure, diabetes, malignancies, liver cirrhosis, prolonged use of nephrotoxic drugs, and simultaneous use of two or more nephrotoxic drugs. Discontinuation of the drug which resulted in kidney failure is the first and foremost principle for managing not only drug-induced, but all AKI patients. The use of potentially nephrotoxic drugs should be avoided, especially in high-risk patients, in order to prevent drug-induced AKI. If a patient needs a drug that affects renal hemodynamics, the therapy should begin with a minimum effective dose, and combinations of two and more nephrotoxic drugs should be avoided. Close monitoring of kidney function is crucial for high-risk patients. They should also be informed about the importance of adequate water consumption schedule for prevention of hypovolemia.

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapy for individuals with cardiorenal disease. They are associated with increased risk of hyperkalaemia, a common and life-threatening disorder for this population. RAASi-induced hyperkalaemia often leads to dose reduction or discontinuation, reducing cardiorenal protection. Guideline recommendations differ between specialties for the clinical management of hyperkalaemia. Using a modified Delphi method, we developed consensus recommendations for optimal management of hyperkalaemia in adults with cardiorenal disease.Methods and Results: An international steering group of cardiologists and nephrologists developed 39 statements regarding hyperkalaemia care, including risk factors and risk stratification, prevention, correction, and cross-specialty coordination. Consensus was determined by agreement on an online questionnaire administered to cardiorenal specialists across Europe and North America. The threshold for consensus agreement was established a priori by the steering group at 67%. Across November 2021, 520 responses were received from Canada (n = 50), France (n = 50), Germany (n = 54), Italy (n = 58), Spain (n = 57), the UK (n = 49), and the US (n = 202); 268 from cardiologists and 252 from nephrologists. Twenty-nine statements attained very high agreement (≥90%) and 10 attained high agreement (≥67%-<90%), with strong alignment between cardiologists and nephrologists.Conclusion: A high degree of consensus regarding hyperkalaemia evaluation and management exists among healthcare professionals. Based on high levels of agreement, the steering group derived six key recommendations for hyperkalaemia prevention and management in people with cardiorenal disease. Future studies examining the quality of hyperkalaemia care delivery are required. [ABSTRACT FROM AUTHOR]

Il n'existe pas de consensus de prise en charge en France pour les patients présentant une hyperkaliémie persistante. Une hétérogénéité des pratiques a été observée. Un consensus sur la définition et la prise en charge de l'hyperkaliémie persistante a été élaboré par un panel Delphi de néphrologues français entre décembre 2019 (26 votants sur 40 sollicités au premier tour) et juin 2020 (20 votants sur 26 au deuxième tour). Une hyperkaliémie persistante malgré les stratégies actuelles peut être définie par la récurrence d'un épisode d'hyperkaliémie deux fois ou plus au cours d'une année malgré le recours, dans la même année, aux résines chélatrices ou aux diurétiques de l'anse disponibles. Différents profils de patients sont à risque de développer une hyperkaliémie persistante (diabète, insuffisance rénale chronique aux stades 3B à 5 non dialysé, insuffisance cardiaque chronique). Il existe un besoin médical non couvert par les stratégies actuelles (dont les résines chélatrices disponibles) pour la prise en charge de l'hyperkaliémie persistante chez les patients traités par inhibiteurs du système rénine-angiotensine-aldostérone. Le panel exprime le besoin de pouvoir recourir à de nouvelles stratégies thérapeutiques validées par des essais thérapeutiques. In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed. A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round). Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins). The panel expressed a need for new treatment strategies validated by clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin-converting enzyme 2 (ACE2) of the renin-angiotensin-aldosterone system (RAAS) serves as a functional receptor to gain entry into the cells for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and ACE2 is a potential virulent factor in infectivity. Our study aimed to ascertain the association of RAAS inhibitors with adverse cardiovascular and other outcomes in hospitalized COVID-19 patients., Methods: This is a retrospective study of medical records of ≥18-year-old patients hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction type 1, acute congestive heart failure, acute stroke) and mortality. Secondary outcomes were respiratory failure, need for and duration of mechanical ventilation, acute deep vein thrombosis or pulmonary embolism (DVT/PE), and readmission rate., Results: Among 376 hospitalized COVID-19 patients, 149 were on RAAS inhibitors. No statistically significant differences were found between RAAS inhibitor and non-RAAS inhibitor groups with respect to acute cardiovascular events (6% vs. 6.2%, p = 0.94), acute DVT/PE (4.7% vs. 4.8%, p = 0.97), hypoxia (62.4% vs. 58.6%, p = 0.46), need for mechanical ventilation (18.1% vs. 16.7%, p = 0.72), mortality (19.5% vs. 22%, p = 0.56), and readmission rate (11.4% vs. 14.1%, p = 0.45). Some nuances discovered were a higher rate of hospitalizations among Native Americans receiving RAAS inhibitors (30.2% vs. 19.8%) and significantly lower levels of procalcitonin in patients on RAAS inhibitors., Conclusions: Among hospitalized patients with COVID-19, those on RAAS inhibitors showed no significant differences in acute cardiovascular events, acute DVT/PE, hypoxia, need for mechanical ventilation, readmission, or mortality rate compared to those not on them. However, further large-scale studies are needed to validate these findings., (© 2024 S. Karger AG, Basel.)

Background Previous data suggest that using renin‐angiotensin‐aldosterone system inhibitors (RAASIs) improves survival in patients with cardiovascular diseases. We sought to investigate the association of different patterns of use of RAASIs on perioperative and 1‐year outcomes following carotid revascularization. Methods and Results We investigated patients undergoing carotid revascularization, either with carotid endarterectomy or transfemoral carotid artery stenting, in the VQI (Vascular Quality Initiative) VISION (Vascular Implant Surveillance and Interventional Outcomes Network) data set between 2003 and 2018. We divided our cohort into 3 groups: (1) no history of RAASI intake, (2) preoperative intake only, and (3) continuous pre‐ and postoperative intake. The final cohort included 73 174 patients; 44.4% had no intake, 50% had continuous intake, and 5.6% had only preoperative intake. Compared with continuous intake, preoperative and no intake were associated with higher odds of postoperative stroke (odds ratio [OR], 1.7 [95% CI, 1.5–1.9]; P

Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59–75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40–0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32–0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4–0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.

BACKGROUND There is controversy over the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on the prognosis in patients with coronavirus disease 2019 (COVID-19), therefore, we aim to further explore the effect of renin–angiotensin–aldosterone system inhibitors on COVID-19-associated disease severity and mortality. METHODS We systematically searched PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv from inception to 6 September 2021. The primary outcome was all-cause mortality. Secondary outcome was severe disease which was defined as admission to the intensive care unit, the use of noninvasive or invasive mechanical ventilation, or death. RESULTS A total of 7 randomized controlled trials involving 1,321 COVID-19 patients were included. Fixed-effects meta-analysis demonstrated that the use of ACEI/ARB was not associated with higher risk of mortality (risk ratio [RR] = 0.84, 95% confidence interval [CI] 0.57–1.22, P = 0.10, I 2 = 43%) and disease severity (RR = 0.86, 95% CI 0.71–1.05, P = 0.11, I 2 = 47%). However, the subgroup analysis showed that compared with no ACEI/ARB use, the use of ARB was associated with a significant reduction of mortality (RR = 0.23, CI 0.09–0.60, P = 0.55, I 2 = 0%) and disease severity (RR = 0.38, CI 0.19–0.77, P = 0.007). CONCLUSIONS In conclusion, based on the available data, ACEI/ARB is not associated with the risk of mortality and disease severity in COVID-19 patients. And ACEI/ARB medications, especially ARB, should not be discontinued for patients with COVID-19. [ABSTRACT FROM AUTHOR]

Abstract Background One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. Results Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. Conclusion Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

Potassium is a major intracellular cation in the body, regulating membrane potential of excitable cells, such as cardiomyocytes and skeletal muscle cells. Because the kidney plays a critical role in controlling potassium balance, the elevation in serum potassium levels is one of the most common complications in patients with maintenance hemodialysis (MHD). In addition to reduced renal potassium excretion, the alteration in body potassium distribution owing to comorbid conditions may also contribute to dyskalemia. Besides potassium elimination through hemodialysis in MHD patients, accumulating data indicate the potential importance of extra‐renal elimination involving the gastrointestinal system, which can be affected by the inhibitors of the renin‐angiotensin‐aldosterone system. In this article, the literature on potassium physiology in MHD patients is reviewed with an emphasis on the changes from individuals with normal kidney function. This article also summarizes the findings of recent studies on dietary control, dialysate prescription, and pharmacological therapy. [ABSTRACT FROM AUTHOR]

Aims: In patients with current or a history of hyperkalaemia, treatment with renin–angiotensin–aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+) binder, may improve serum K+ levels and adherence to RAASi. Methods: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single‐blinded run‐in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run‐in phase will last up to 12 weeks, following which patients will undergo double‐blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator‐reported adverse events of hyperkalaemia, hyperkalaemia‐related clinical endpoints and an overall RAASi use score (using a 0–8‐point scale) comprising all‐cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. Conclusion: The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use. [ABSTRACT FROM AUTHOR]

Background: Henoch–Sch€onlein purpura nephritis often resolves spontaneously, without treatment, making decisions regarding therapeutic interventions difficult. Methods: Fifty-four patients who were diagnosed as having Henoch–Sch€onlein purpura nephritis between April 2004 and March 2018, and developed hematuria and/or proteinuria, were studied retrospectively. The observation period ended at the disappearance of hematuria or proteinuria, or the last observation date before December 2019 for each patient. Twenty-four of the patients received no treatment (Group A), 19 underwent renin-angiotensinaldosterone system inhibitors only (B), 4 experienced steroid pulse therapy and combination therapy only (C) and the remaining 7 received steroid pulse therapy and combination therapy following renin-angiotensin-aldosterone system inhibitors (C). Clinical characteristics were examined according to the treatment method. Survival analysis for persistent urinary abnormalities was performed according to treatment modality, with multiple treatment records created per subject, if necessary. Results: The highest urine protein/creatinine levels were significantly higher in groups B and C than in group A. The lowest estimated glomerular filtration rate was not significantly different among the three groups. In groups A and B, proteinuria resolved in >90% of patients. Survival analysis showed that steroid pulse therapy and combination therapy was not related to the better resolution of hematuria or proteinuria than renin-angiotensin-aldosterone system inhibitors. Conclusions: Several patients with Henoch–Sch€onlein purpura nephritis went into remission either without treatment or with renin-angiotensin-aldosterone system inhibitors alone. The treatment plan for patients with Henoch– Sch€onlein purpura nephritis needs to be determined carefully. [ABSTRACT FROM AUTHOR]

Renin–angiotensin–aldosterone system (RAAS) inhibitors are the key medications for patients with heart failure and chronic kidney disease. Multiple randomized controlled trials have demonstrated their benefits in an outpatient setting for the treatment of chronic heart failure. Additional advantages in acute heart failure treatment during inpatient hospitalization are less clear but a small number of non-randomized studies have favored their use. Conditions that result in stoppage of RAAS inhibitors during inpatient stay are an increase in serum creatinine, hyperkalemia, and hemodynamic instability such as hypotension. The role of RAAS inhibitors in chronic kidney disease has also been documented in multiple randomized controlled trials, with their use in hypertension and proteinuria being unambiguous. This narrative review summarizes the role of RAAS inhibitors in acute and chronic heart failure and chronic kidney disease.

The novel coronavirus infection (COVID-19) caused by the b-coronavirus SARS-CoV-2, and leads to acute respiratory distress-syndrome, has affected more than nineteen million people worldwide, resulting in 0.7 million deaths as of August 2020. The fact that the virus uses angiotensin-converting enzyme 2 as a receptor for entering the target cell, and the high prevalence of hypertension and other cardiovascular diseases among patients with COVID-19, have caused serious discussions on the management of such patients. This consensus of experts from the Russian Medical Society for Arterial Hypertension analyzed the existing data on the relationship between COVID-19 and hypertension, the pathophysiological aspects of the penetration of the virus into target cells and the use of renin-angiotensin-aldosterone system inhibitors in patients with hypertension and COVID-19.

Aims: Antihypertensive drugs have been implicated in coronavirus disease 2019 (COVID‐19) susceptibility and severity, but estimated associations may be susceptible to bias. We aimed to evaluate antihypertensive medications and COVID‐19 diagnosis and mortality, accounting for healthcare‐seeking behaviour. Methods: A population‐based case‐control study was conducted including 16 866 COVID‐19 cases and 70 137 matched controls from the UK Clinical Practice Research Datalink. We evaluated all‐cause mortality among COVID‐19 cases. Exposures were angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta‐blockers (B), calcium‐channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). Analyses were adjusted for covariates and consultation frequency. Results: ACEIs were associated with lower odds of COVID‐19 diagnosis (adjusted odds ratio [AOR] 0.82, 95% confidence interval [CI] 0.77‐0.88) as were ARBs (AOR 0.87, 95% CI 0.80‐0.95) with little attenuation from adjustment for consultation frequency. C and D were also associated with lower odds of COVID‐19 diagnosis. Increased odds of COVID‐19 for B (AOR 1.19, 95% CI 1.12‐1.26) were attenuated after adjustment for consultation frequency (AOR 1.01, 95% CI 0.95‐1.08). Patients treated with ACEIs or ARBs had similar odds of mortality (AOR 1.00, 95% CI 0.83‐1.20) to patients treated with classes B, C, D or O or patients receiving no antihypertensive therapy (AOR 0.99, 95% CI 0.83‐1.18). Conclusions: There was no evidence that antihypertensive therapy is associated with increased risk of COVID‐19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID‐19 diagnosis. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), the first pandemic caused by a human infecting coronavirus, has drawn global attention from the first time it appeared in Wuhan city of China in late December 2019. Detection of the responsible viral pathogen, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by WHO, and its possible pathogenesis lead to the forming of many hypotheses about the factors that may affect the patients' outcome. One of the SARS-CoV-2 infection concerns was the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19 patients' morbidity and mortality. Studies demonstrated that because SARS-CoV-2 uses human ACE2 cell receptors as an entry receptor to invade the cells, there might be an association between antihypertensive drugs such as RAAS inhibitors (specifically ACEIs and ARBs) and the COVID-19 disease. Data are scarce and conflicting regarding ACEI or ARB consumption and how it influences disease outcomes, and a single conclusion has not been reached yet. According to the literature review in our article, the most evidentially supported theory about the use of RAAS inhibitors in COVID-19 is that these medications, including ACEI/ARB, are not associated with the increased risk of infection, disease severity, and patient prognosis. However, further studies are needed to support the hypothesis. [ABSTRACT FROM AUTHOR]

Background Hyperkalaemia (HK) is a common electrolyte disorder in patients with chronic kidney disease (CKD) and/or treated with renin–angiotensin–aldosterone system inhibitors (RAASis). The aim of this study is to determine the severity, current management and cost of chronic HK. Methods We performed a retrospective cohort study of patients with chronic HK and CKD, heart failure or diabetes mellitus between 2011 and 2018. The study follow-up was 36 months. Results A total of 1499 patients with chronic HK were analysed: 66.2% presented with mild HK, 23.4% with moderate HK and 10.4% with severe HK. The severity was associated with CKD stage. Most patients (70.4%) were on RAASi therapies, which were frequently discontinued (discontinuation rate was 39.8, 49.8 and 51.8% in mild, moderate and severe HK, respectively). This RAASi discontinuation was similar with or without resin prescription. Overall, ion-exchange resins were prescribed to 42.5% of patients with HK and prescriptions were related to the severity of HK, being 90% for severe HK. Adherence to resin treatment was very low (36.8% in the first year and 17.5% in the third year) and potassium remained elevated in most patients with severe HK. The annual healthcare cost per patient with HK was €5929, reaching €12 705 in severe HK. Costs related to HK represent 31.9% of the annual cost per HK patient and 58.8% of the specialized care cost. Conclusions HK was usually managed by RAASi discontinuation and ion-exchange resin treatment. Most patients with HK were non-adherent to resins and those with severe HK remained with high potassium levels, despite bearing elevated healthcare expenditures. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is the most common chronic primary glomerulonephritis in both children and adults, and 20–30% of patients with persistent hematuria/proteinuria progress to kidney failure within 20 years. In Japan, most cases of childhood IgAN are detected by school screening programs during the early onset of the disease when hematuria/proteinuria are asymptomatic and kidney function is normal. Therefore, it is possible to follow the detailed clinical course and appropriate therapeutic interventions from early onset of the disease. Data on non-immunosuppressive therapies for children with IgAN are highly limited. The Japanese Pediatric IgA Nephropathy Treatment Study Group was organized in 1989 to conduct clinical trials and accumulate data on treatments for childhood IgAN. In this review, we focus on non-immunosuppressive therapies, notably with renin-angiotensin-aldosterone system (RAAS) inhibitors for childhood IgAN and related clinical trials conducted primarily in Japan. We also describe the anti-inflammatory and antiproteinuric effects of RAAS inhibitors in IgAN, differences in treatment regimens because of the acute and active pathological features of childhood IgAN, adverse events of RAAS inhibitors, other non-immunosuppressive treatment options, and future directions. [ABSTRACT FROM AUTHOR]

L'hyperkaliémie récidivante peut conduire à une sous-utilisation des inhibiteurs du système rénine-angiotensine-aldostérone. Nous présentons une analyse des données françaises de l'étude PROKALE, qui a évalué la prise en charge de l'hyperkaliémie dans cinq pays européens. Un examen rétrospectif des dossiers de patients adultes non dialysés ayant présenté au moins deux épisodes d'hyperkaliémie ≥ 5,5 mEq/L sur une période de 12 mois a été effectué. En France, 115 médecins (57 néphrologues et 58 cardiologues) ont participé à l'étude, et 295 patients ont été étudiés. L'âge moyen était de 68 ans ; 212 patients (71,9 %) avaient une insuffisance rénale chronique, 108 (36,6 %) une insuffisance cardiaque chronique et 102 (34,6 %) un diabète sucré. Le nombre moyen d'épisodes hyperkaliémiques rapportés était de 2,3. Sur 90 hospitalisations, 24 (26,7 %) étaient directement liées à un épisode d'hyperkaliémie. Les traitements utilisés dans la prise en charge de l'hyperkaliémie lors du premier épisode étaient les diurétiques de l'anse (144 patients [48,8 %]), les résines échangeuses de cations (135 [45,8 %]), un régime pauvre en potassium (31 [10,5 %]) ou le bicarbonate de sodium (31 [10,5 %]). Entre les deux épisodes d'hyperkaliémie consécutifs documentés, la proportion des patients traités par des inhibiteurs du système rénine-angiotensine-aldostérone a diminué de 42,4 % à 34,6 %. Des interruptions du traitement par les inhibiteurs du système rénine-angiotensine-aldostérone sont observées en contexte d'hyperkaliémie récidivante. L'hyperkaliémie récidivante représente une cause majeure d'hospitalisation. Des stratégies de prise en charge plus efficaces sont nécessaires. Recurrent hyperkalaemia may result in underutilisation of renin-angiotensin-aldosterone system inhibitors. We report an analysis of French data from the PROKALE retrospective study, which assessed the management of recurrent hyperkalaemia in five European countries. A retrospective chart review including patients not on dialysis with two or more hyperkalaemia episodes ≥ 5.5 mEq/L documented within a 12-month observation period was performed. In France, 115 physicians (57 nephrologists et 58 cardiologists) participated in the study and 295 patients were studied in this analysis. Mean age was 68 years; 212 patients (71.9%) had chronic kidney disease, 108 (36.6%) had chronic heart failure and 102 (34.6%) had diabetes mellitus. The mean number of documented hyperkalaemic episodes was 2.3. A total of 90 hospitalizations occurred during the observation period, of which 24 (26.7%) were directly related to a hyperkalaemic episode. At the time of the first documented hyperkalaemic episode, measures used for the management of hyperkalaemia included loop diuretics (144 patients [48.8%]), sodium/calcium polystyrene sulphonate (135 patients [45.8%]), a low-potassium diet (31 patients [10.5%]) and sodium bicarbonate (31 patients [10.5%]). Between the two consecutive hyperkalaemic episodes documented, the proportion of patients on renin-angiotensin-aldosterone system inhibitors treatment decreased from 42.4% to 34.6%. Renin-angiotensin-aldosterone system inhibitors treatment interruptions were observed in the setting of recurrent hyperkalaemic episodes. Recurrent hyperkalaemia is a major cause of hospitalizations. More effective strategies for the prevention of recurrent hyperkalaemia are needed. [ABSTRACT FROM AUTHOR]

Background Sepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin‐angiotensin‐aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes. Methods and Results A total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all‐cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all‐cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62–0.75), MACEs (HR, 0.87; 95% CI, 0.81–0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76–0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61–0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77–0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results. Conclusions In our study, we found that RAASi users had reduced risks of all‐cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

Coronavirus disease 2019 (COVID-19), the first pandemic caused by a human infecting coronavirus, has drawn global attention from the first time it appeared in Wuhan city of China in late December 2019. Detection of the responsible viral pathogen, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by WHO, and its possible pathogenesis lead to the forming of many hypotheses about the factors that may affect the patients’ outcome. One of the SARS-CoV-2 infection concerns was the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19 patients’ morbidity and mortality. Studies demonstrated that because SARS-CoV-2 uses human ACE2 cell receptors as an entry receptor to invade the cells, there might be an association between antihypertensive drugs such as RAAS inhibitors (specifically ACEIs and ARBs) and the COVID-19 disease. Data are scarce and conflicting regarding ACEI or ARB consumption and how it influences disease outcomes, and a single conclusion has not been reached yet. According to the literature review in our article, the most evidentially supported theory about the use of RAAS inhibitors in COVID-19 is that these medications, including ACEI/ARB, are not associated with the increased risk of infection, disease severity, and patient prognosis. However, further studies are needed to support the hypothesis.

Background: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support., Methods and Results: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m 2 , wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P =0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P =0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively)., Conclusions: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3–5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to p value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73–17,276). The median follow-up was 38 months (range 24–58). The overall median of both primary and secondary outcomes was 0 (range 0–117 and range 0–55, respectively). The median of FI for primary and secondary outcomes with a p value lower than 0.05 was 6 (range: 1–117) and 7.5 (range: 1–55), respectively. The medians of the FI for primary outcomes with a p value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1–117) and 22 (range 1–80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD.