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Frontiers in Medicine 2022Patients with end-stage renal disease (ESRD) are characterized with high risk of heart failure. Although mineralocorticoid receptor antagonists have beneficial effect on...
BACKGROUND
Patients with end-stage renal disease (ESRD) are characterized with high risk of heart failure. Although mineralocorticoid receptor antagonists have beneficial effect on relieving cardiac fibrosis and, thus, reduce the incidence of cardiovascular disease and cardiac death, the therapeutic benefits and adverse effects are still controversial. We conducted a meta-analysis to measure the safety and efficacy of spironolactone in patients undergoing dialysis.
METHODS
A systematic search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Cochrane databases. Primary outcomes included changes in all-cause mortality (ACM), serum potassium concentration, incidence of hyperkalemia and gynecomastia (GYN). Secondary outcomes included changes in blood pressure (BP), left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Subgroup analysis and sensitivity analysis were further conducted. This research was registered with PROSPERO (International Prospective Register of Systematic Reviews; No. CRD42021287493).
RESULTS
Fifteen RCTs with 1,258 patients were enrolled in this pooled-analysis. Spironolactone treatment significantly decreased ACM (RR = 0.42, < 0.0001), CCV (RR = 0.54, = 0.008) and LVMI (MD = -6.28, = 0.002), also increased occurrence of GYN (RR = 4.36, = 0.0005). However, LVEF (MD = 2.63, = 0.05), systolic BP (MD = -4.61, = 0.14) and diastolic BP (MD = -0.12, = 0.94) did not change between two groups after treatment. Although serum potassium concentration was increased (MD = 0.22, < 0.0001) after spironolactone supplement, the risk of hyperkalemia remained unchanged (RR = 1.21, = 0.31). Further subgroup analysis found more obvious advantageous as well as disadvantageous effects in Asian subjects than European or American ones. Also, with more than 9 months of treatment duration, patients achieved more favorable influence than shorter duration.
CONCLUSIONS
These results highlight the therapeutic effects of spironolactone on cardiovascular indexes, including ACM, CCV, and LVMI. However, the unignorable increase of GYN incidence and serum potassium level indicate that close monitor in dialysis-dependent patients, especially Asian patients, is essential.
PubMed: 35372414
DOI: 10.3389/fmed.2022.828189 -
Frontiers in Cardiovascular Medicine 2021The medical treatments of chronic heart failure have made remarkable progress in recent years. It is crucial to determine the optimal drug combination based on current...
The medical treatments of chronic heart failure have made remarkable progress in recent years. It is crucial to determine the optimal drug combination based on current evidence. A search of PubMed, EMBASE, and Cochrane CENTRAL databases was conducted for studies on angiotensin receptor-neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and ivabradine (IVA) between 1987 and 2021. The network meta-analysis was performed to compare the efficacy of drug therapies in heart failure with reduced ejection fraction (HFrEF). Forty-eight randomized controlled trials (RCTs), which overall included 68,074 patients with HF and left ventricular ejection fraction (LVEF) ≤ 40%, were identified and included in the network meta-analysis. The efficacies of 13 intervention classes, including monotherapies or combinations of ACEI, ARB, ARNI, BB, MRA, SGLT2i, IVA, and placebo, on hospitalization for HF, cardiovascular mortality, and all-cause mortality were compared. Among the 13 included interventions, ARNI+BB+MRA, SGLT2i+ACEI+BB+MRA, and IVA+ACEI+BB+MRA were found to be best in terms of all three outcomes. Compared with placebo, these three drug combinations were associated with significant reductions in the risk of all-cause death, cardiovascular mortality and hospitalization for HF. ARNI+BB+MRA, SGLT2i+ACEI+BB+MRA, and IVA+ACEI+BB+MRA were the top three therapies for patients with HFrEF. The increasing use of combinations of conventional and novel drugs contributed to progressive reductions in hospitalization and mortality in patients with HFrEF.
PubMed: 35097007
DOI: 10.3389/fcvm.2021.787810 -
International Journal of Molecular... Jan 2022Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and... (Review)
Review
Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20-356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions.
Topics: Adrenal Gland Neoplasms; Contrast Media; Diagnosis, Differential; Humans; Radiographic Image Interpretation, Computer-Assisted; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 35054823
DOI: 10.3390/ijms23020637 -
JACC. Heart Failure Feb 2022This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction.
BACKGROUND
The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized.
METHODS
We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]).
RESULTS
We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses.
CONCLUSIONS
In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.
Topics: Aged; Angiotensin Receptor Antagonists; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Stroke Volume
PubMed: 34895860
DOI: 10.1016/j.jchf.2021.09.004 -
Cardiovascular Therapeutics 2021A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. (Meta-Analysis)
Meta-Analysis
BACKGROUND
A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking.
OBJECTIVE
To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI.
METHODS
Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020.
RESULTS
15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); = 0.002) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), < 0.00001) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), < 0.0001). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), = 0.007) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), = 0.002). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), < 0.00001), left ventricular end-systolic index (MD: -4.52 ml/m, 95% CI (-8.21, -0.83), = 0.02), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), = 0.05). The corresponding RR were 1.72 (95% CI (1.43, 2.07), < 0.00001) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction).
CONCLUSIONS
Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.
Topics: Aldosterone; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Stroke Volume; Ventricular Function, Left
PubMed: 34786023
DOI: 10.1155/2021/1710731 -
Antimicrobial Agents and Chemotherapy Jan 2022We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in real-world practice....
We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in real-world practice. First, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the signal differences of triazoles-related AME. Second, a systematic review was conducted, and clinical features of AME cases reported in clinical practice were described. In the FAERS database, we identified 27 cases of triazoles-AME, posaconazole [ROR = 865.37; 95%CI (464.14; 1613.45)], and itraconazole [ROR = 556.21; 95% (303.05; 1020.85)] significantly increased the risk of AME events, while fluconazole, voriconazole, and isavuconazole did not affect any of the mineralocorticoid excess targets. Eighteen studies with 39 cases raised evidence of AME following posaconazole and itraconazole treatment, and another 27 cases were identified by analysis of the description of clinical features in the FAERS database. The average age of 66 patients was 55.5 years (6-87 years). AME mainly occurs in patients with posaconazole concentrations above 3 μg/mL (mean = 4.4 μg/mL, range 1.8∼9.5 μg/mL), and is less likely to occur when levels are below 2 μg/mL (6%). The median time to event onset was 11.5 weeks, and 50% of the adverse events occurred within 3 months for posaconazole. The presented study supports very recent findings that posaconazole and itraconazole, but not the other three azole antifungals investigated, are associated with AME and that the effects are dose-dependent, which allows for a dose de-escalation strategy and for substitution with fluconazole, isavuconazole, or voriconazole to resolve the adverse effects.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Azoles; Child; Humans; Itraconazole; Middle Aged; Mineralocorticoid Excess Syndrome, Apparent; Voriconazole; Young Adult
PubMed: 34662186
DOI: 10.1128/AAC.01668-21 -
Cancers Oct 2021Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this... (Review)
Review
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3-6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3-6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.
PubMed: 34638485
DOI: 10.3390/cancers13195001 -
Frontiers in Medicine 2021This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results...
Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.
This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium ( = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) ( = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.
PubMed: 34490289
DOI: 10.3389/fmed.2021.686729 -
ESC Heart Failure Oct 2021We systematically reviewed the European real-world evidence (RWE) about sacubitril-valsartan for heart failure with reduced ejection fraction. (Meta-Analysis)
Meta-Analysis
AIMS
We systematically reviewed the European real-world evidence (RWE) about sacubitril-valsartan for heart failure with reduced ejection fraction.
METHODS AND RESULTS
Twenty-one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM-HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random-effects model meta-analysis, age was higher (mean difference +3.84, 95% CI 1.92-5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64-0.91), hypertension (OR 0.55, 95% CI 0.37-0.82), and diabetes (OR 0.77, 95% CI 0.64-0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27-5.53) in real-life than in PARADIGM-HF. Other clinical and medical features were presented in 19-76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril-valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23-47) and discontinued in 12.8% (95% CI 7.4-18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all-cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5-19)/100 person-year, 8 (95% CI 4-12)/100 person-year, and 24 (95% CI 5-42)/100 person-year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects).
CONCLUSIONS
Limited-quality RWE indicates that there are important differences between European patients prescribed sacubitril-valsartan and the PARADIGM-HF population, including the frequency of target dose achievement.
Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Stroke Volume; Treatment Outcome; Valsartan
PubMed: 34338429
DOI: 10.1002/ehf2.13547 -
Frontiers in Pharmacology 2021Cardiovascular events are one of the most serious complications that increase the risk of mortality and morbidity in pre-dialysis and on-dialysis chronic kidney disease...
Systematic Review and Meta-Analysis of Renin-Angiotensin-Aldosterone System Blocker Effects on the Development of Cardiovascular Disease in Patients With Chronic Kidney Disease.
Cardiovascular events are one of the most serious complications that increase the risk of mortality and morbidity in pre-dialysis and on-dialysis chronic kidney disease (CKD) patients. Activation of the renin-angiotensin-aldosterone system (RAAS) is considered to contribute to the development of cardiovascular events in these populations. Therefore, several kinds of RAAS blockers have been frequently prescribed to prevent cardiovascular events in patients with CKD; however, their effectiveness remains controversial. This systematic review focuses on whether RAAS blockers prevent cardiovascular events in patients with CKD. PubMed were searched to retrieve reference lists of eligible trials and related reviews. Randomized prospective controlled trials that investigated the effects on cardiovascular events in CKD patients that were published in English from 2010 to 2020 were included. Among 167 identified studies, 11 eligible studies ( = 8,322 subjects) were included in the meta-analysis. The meta-analysis showed that RAAS blockers significantly reduced cardiovascular events in on-dialysis patients with CKD [three studies; odds ratio (OR), 0.52; 95% confidence interval (CI), 0.36 to 0.74; = 0.0003], but there was no significant difference in pre-dialysis patients with CKD because of the heterogeneity in each study (eight studies). We also investigated the effects of each kind of RAAS blocker on cardiovascular events in CKD patients. Among the RAAS blockers, mineralocorticoid receptor antagonists significantly decreased cardiovascular events in pre-dialysis or on-dialysis patients with CKD (four studies; OR, 0.60; 95%CI, 0.50 to 0.73, < 0.0001). However, angiotensin receptor blockers did not show significant effects (four studies; OR, 0.65; 95%CI, 0.42 to 1.01; = 0.0529). The effects of angiotensin converting enzyme inhibitors and direct renin inhibitors on cardiovascular events in patients with CKD could not be analyzed because there were too few studies. Mineralocorticoid receptor antagonists may decrease cardiovascular events in pre-dialysis or on-dialysis patients with CKD.
PubMed: 34276363
DOI: 10.3389/fphar.2021.662544