Khanal, Resha

Background: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to prevent atrial fibrillation (AF). However, inconsistent results of MRAs effect on perioperative AF have been reported in the literature in patients undergoing cardiac surgery. To our knowledge, this is the first metanalysis to assess the effect of MRAs on occurrence of perioperative AF in patients undergoing cardiac surgery. Method: We searched different electronic databases from inception to April 30th, 2023, for randomized controlled trials (RCTs) and observational studies that evaluated the use of MRAs in patients with heart failure and left ventricular ejection fraction (LVEF) 30-50% who were referred for Coronary Artery Bypass Grafting (CABG) and/or valve surgery without any AF history. Primary outcome was occurrence of perioperative AF. Three independent reviewers selected and appraised the data. A random-effects meta-analysis was performed to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Result: We included 4 studies, 1 RCT and 3 observational cohorts, with a cumulative number of 1,128 patients with mean age 65.15 years. 412(36.5%) received an MRA (spironolactone or eplerenone). The follow up duration was 5 days to 1 month. During follow-up, 118 (28.64%) patients treated with MRAs, developed AF, compared to 224 (31.28%) patients, without MRA treatment. However, metanalysis showed that there is no significant reduction in occurrence of perioperative AF in MRA treated patients (OR: 0.88 CI: 0.58-1.33 p=0.55), I2 53%; Figure] Conclusion: Experimental data have shown that MRA blockade prevents perioperative AF in animal models but our metanalysis demonstrated that MRAs were not protective for perioperative AF in patients undergoing cardiac surgery. Larger trials in humans are warranted to evaluate its efficacy, particularly in patients undergoing cardiac surgery.

Background: Inclisiran is a first-in-class, cholesterol-lowering small interfering RNA based therapy for treatment of atherosclerosis or familial hypercholesterolemia as an adjunct to maximally tolerated statin therapy. Since approval by FDA in December 2021, it is getting increasingly popular due to biannual regimen. During trials and upon review for FDA approval, it exhibited injection site reaction, arthralgia, urinary tract infection, diarrhea, and dyspnea. Objective: In view of increased usage, it is important to establish a side effect profile of inclisiran in general population since the ORION 9, 10 and 11 trials. Methods: We explored reported adverse events (AEs) of inclisiran using FDA Adverse Event Reporting System (FAERS). A total of 472 AEs were reported until September 2022. 44.49% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (35.2%) vs women (45.2%) and in three age groups of 18-64, 65-85, and >85 years. Results: A total of 100 (47%) events were serious including 38% hospitalization and 14% deaths. The most frequently reported AE was surprisingly dyspnea in conjunction with cough (21.9%) followed by myalgia (15.2%), injection site pain (5.2%), arthralgia (4.3%), diarrhea (4.3%), rash (3.3%) and fatigue (2.4%). Most AEs were consistent with ORION trial except elevated LDL (8.2%), acute myocardial infarction (AMI) (7.6%), hyponatremia (6.6%), acute kidney injury (AKI) (3.3%) and headache (2.4%). It was reported more in women of age group 65-85 years. Discussion: The events of death and hospitalization after initiating inclisiran could have been associated with AMI, AKI and hyponatremia that are newly reported since the trial, however the temporality and mechanisms are unknown. Even though the trial has shown that this drug is relatively safe, physicians must be vigilant about the new developments to avoid decompensation in vulnerable patients. Its use in patients with pulmonary disease can worsen dyspnea. Conclusion: With the current increasing use of inclisiran, there is a need for more data on safety profile. In future, further randomized trials are required to better assess the safety profile focusing on temporality and mechanisms of AMI and AKI in relation to inclisiran.

AbstractObjectiveMediterranean diet has been shown to be associated with lower risk of cardiovascular disease. However, its association with chronic kidney disease (CKD) remains inconclusive as the results were not consistent among population‐based studies. This study aims to assess the association between Mediterranean diet adherence and CKD prevention.MethodsWe performed a systematic review and meta‐analysis of studies describing the risk for CKD in community‐dwelling subjects ≥18 years of age. Mediterranean diet adherence was assessed by standardized food frequency questionnaires. The search was conducted through MEDLINE, EMBASE and Cochrane Library.ResultsOf 168 citations, a total of nine (n = 19 151) and four studies (n = 8467) were included in the systematic review and meta‐analysis, respectively. Only studies adopting Mediterranean Diet Scale (MDS) were included in the analysis. The mean score was 3.8 ± 0.3 points. With the mean follow‐up duration of 20.6 ± 7.0 years, the pooled odds ratio (OR) for CKD was 0.901 (95% confidence interval [CI] 0.868‐0.935) for each 1‐point increment of MDS. The incidence of CKD was 0.026 events per person‐year (95% CI 0.008‐0.045). Moreover, male sex was associated with the incidence of CKD in an adjusted meta‐regression analysis. In contrast, there was no significant association between age, black race, smoking, diabetes, hypertension estimated glomerular filtration rate and total daily energy intake vs CKD incidence.ConclusionAdherence to Mediterranean diet by a 1‐point increment of MDS was associated with 10% lower risk of CKD. However, there were insufficient data on patients with pre‐existing CKD or dialysis.

AbstractThe clinical use of continuous bumetanide infusion for acute heart failure and volume overload is common. However, there is not enough supporting evidence for the use of continuous bumetanide infusion. Thus, we conducted this systematic review and meta‐analysis aiming to describe the treatment outcomes of continuous bumetanide infusion. We searched Ovid MEDLINE, EMBASE and the Cochrane Library for eligible publications. Inclusion criteria were patients age ≥18 years with bumetanide infusion for heart failure, acute kidney injury (AKI) or volume overload. From 1564 citations, three studies (n = 94 patients) were included in the systematic review and meta‐analysis. The mean dose of bumetanide was 1.08 ± 0.43 mg/hour with a mean treatment duration of 45.09 ± 10.12 hours. Mean urine output in response to continuous bumetanide infusion was 1.88 mL/kg/hour (95% confidence interval [CI], 1.72‐2.05). The incidence of AKI with continuous bumetanide infusion was 24.7% (95% CI, 8.2‐54.6). By using Pearson's correlation coefficient, increasing doses of bumetanide were correlated with increased urine output (P = .026) and increased incidence of AKI (P < .01). There was no correlation between increasing urine output and the incidence of AKI (P = .739). In conclusion, with available evidence, continuous bumetanide infusion may be used in the treatment of acute heart failure or volume overload with close monitoring for new‐onset or worsening AKI.