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ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
CNS Neuroscience & Therapeutics Jul 2023Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta-analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment.
METHODS
Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle.
RESULTS
Meta-analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin-antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta-analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1-INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose- and time-dependent manner in the MCAO models.
CONCLUSIONS
Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1-INH and FUT175 could be potential medications for IS.
Topics: Animals; Serpins; Biomarkers; Models, Animal; Stroke
PubMed: 37017398
DOI: 10.1111/cns.14205 -
Journal of the American Heart... Jun 2022Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction... (Meta-Analysis)
Meta-Analysis Review
Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID-19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor-COVID-19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID-19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin-converting enzyme inhibitors or angiotensin II type-I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed-effects meta-analyses, only from studies without critical risk of bias that assessed severe COVID-19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta-analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin-converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66-0.87; <0.001; angiotensin II type-I receptor blockers: HR, 0.86; 95% CI, 0.77-0.97; =0.015) and intubation or death (angiotensin-converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48-0.85; =0.002; angiotensin II type-I receptor blockers: HR, 0.74; 95% CI, 0.58-0.95; =0.019) with COVID-19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID-19 research, raising an important question: Were research methods and/or peer-review processes temporarily weakened during the surge of COVID-19 research or is this lack of rigor a systemic problem that also exists outside pandemic-based research? Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021237859.
Topics: Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; COVID-19; Humans; Hypertension; Renin; Renin-Angiotensin System; SARS-CoV-2
PubMed: 35624081
DOI: 10.1161/JAHA.122.025289 -
Scientific Reports Oct 2022Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the... (Meta-Analysis)
Meta-Analysis
Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant..
Topics: Humans; Acute Disease; Pancreatitis; Protease Inhibitors; Randomized Controlled Trials as Topic; Somatostatin
PubMed: 36289288
DOI: 10.1038/s41598-022-22341-7 -
European Stroke Journal Mar 2023Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke.
PATIENTS AND METHODS
We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups.
RESULTS
Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16).
DISCUSSION AND CONCLUSION
People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.
Topics: Humans; Dabigatran; Antithrombins; Ischemic Stroke; Brain Ischemia; Thrombolytic Therapy; Stroke; Anticoagulants; Intracranial Hemorrhages; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 37021155
DOI: 10.1177/23969873221131635 -
BMC Cardiovascular Disorders Jun 2023In recent years, the incidence of diabetes mellitus has been increasing annually, and cardiovascular complications secondary to diabetes mellitus have become the leading... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, the incidence of diabetes mellitus has been increasing annually, and cardiovascular complications secondary to diabetes mellitus have become the leading cause of death in diabetic patients. Considering the high incidence of type 2 diabetes (T2DM) combined with cardiovascular disease (CVD), some new hypoglycemic agents with cardiovascular protective effects have attracted extensive attention. However, the specific role of these regimens in ventricular remodeling remains unknown. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with T2DM and/or CVD.
METHODS
Articles published prior to 24 August 2022 were retrieved in four electronic databases: the Cochrane Library, Embase, PubMed, and Web of Science. This meta-analysis included randomized controlled trials (RCTs) and a small number of cohort studies. The differences in mean changes of left ventricular ultrasonic parameters between the treatment and control groups were compared.
RESULTS
A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. GLP-1RA was more significantly associated with improvement in left ventricular end-systolic diameter (LVESD) [MD = -0.38 mm, 95% CI (-0.66, -0.10)] and LV mass index (LVMI) [MD = -1.07 g/m, 95% CI (-1.71, -0.42)], but significantly decreased e' [MD = -0.43 cm/s 95% CI (-0.81, -0.04)]. DPP-4i was more strongly associated with improvement in e' [MD = 3.82 cm/s, 95% CI (2.92,4.7)] and E/e'[MD = -5.97 95% CI (-10.35, -1.59)], but significantly inhibited LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. SGLT-2i significantly improved LVMI [MD = -0.28 g/m, 95% CI (-0.43, -0.12)] and LV end-diastolic diameter (LVEDD) [MD = -0.72 ml, 95% CI (-1.30, -0.14)] in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function.
CONCLUSION
The results of the network meta-analysis provided high certainty to suggest that SGLT-2i may be more effective in cardiac remodeling compared to GLP-1RA and DPP-4i. While GLP-1RA and DPP-4i may have a tendency to improve cardiac systolic and diastolic function respectively. SGLT-2i is the most recommended drug for reversing ventricular remodeling in this meta-analysis.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Network Meta-Analysis; Protease Inhibitors; Ventricular Remodeling
PubMed: 37296380
DOI: 10.1186/s12872-023-03324-6 -
Medicina (Kaunas, Lithuania) Jun 2023Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has... (Meta-Analysis)
Meta-Analysis Review
Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has generated controversy due to their possible influence on the health status of chronic patients infected with COVID-19. The objective of this work is to analyze the influence of COVID-19 on chronic hypertensive patients treated with ACEI and ARAII inhibitors. A systematic review and meta-analysis in the databases Pubmed, Pro-Quest and Scopus were carried out. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search equation descriptors were obtained from the Medical Subject Headings (MeSH) thesaurus. The search equation was: "Older AND hypertension AND (COVID-19 OR coronavirus) AND primary care" and its equivalent in Spanish. Nineteen articles were obtained, with n = 10,806,159 subjects. Several studies describe the COVID-19 association with ACEI or ARAII treatment in hypertension patients as a protective factor, some as a risk factor, and others without a risk association. In the case of ACEI vs. ARAII, the risk described for the former has an odds ratio (OR) of 0.55, and for ARAII, an OR of 0.59. Some authors talk about mortality associated with COVID-19 and ACEI with a half ratio (HR) of 0.97, and also associated ARAIIs with an HR of 0.98. It is recommended to maintain the use of the renin-angiotensin-aldosterone axis in the context of the COVID-19 disease.
Topics: Humans; Aged; COVID-19; Angiotensin Receptor Antagonists; SARS-CoV-2; Angiotensin-Converting Enzyme Inhibitors; Hypertension
PubMed: 37512012
DOI: 10.3390/medicina59071200 -
Current Problems in Cardiology May 2023Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and... (Review)
Review
Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists; Heterocyclic Compounds, 2-Ring; Heart Failure; Stroke Volume
PubMed: 36623755
DOI: 10.1016/j.cpcardiol.2023.101586 -
The Australasian Journal of Dermatology Feb 2020There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase-4 inhibitors (DPPIs) for diabetes and... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVE
There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase-4 inhibitors (DPPIs) for diabetes and the onset of bullous pemphigoid (BP). The aim of this study was to assess the association between DPPI use and BP, and whether this varied according to DPPI type.
METHODS
We performed a systematic review and meta-analysis according to PRISMA guidelines. We identified five studies with cases and controls. We performed unadjusted and adjusted meta-analyses to assess the potential association.
RESULTS
Adjusted meta-analysis revealed significant association between DPPI use and BP (OR 2.13, 95% CI 1.59-2.86, I = 46%, P < 0.00001). This association was stronger between vildagliptin and BP (OR 5.08, 95% CI 1.70-15.19, P = 0.004) compared to linagliptin (OR 2.87, 95%CI 1.06-7.79, P = 0.04), and no association was found between sitagliptin and BP (OR 1.29, 95%CI 0.79-2.08, P = 0.31). Subgroup analysis demonstrated that the association between DPPI use and BP remained significant in males (OR 2.35, 95% CI 1.46-3.78, P = 0.0005) and females (OR 1.88, 95%CI 1.10-3.22, P = 0.02).
CONCLUSIONS
Limitations were that studies reviewed were retrospective by design which are susceptible to bias and lack of randomisation. Our adjusted analysis supports a significant association between DPPI use and onset of bullous pemphigoid. Vildagliptin had the highest odds of BP. These findings have clinical implications for dermatologists and the management of patients with diabetes and being treated with DPPI agents.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Linagliptin; Pemphigoid, Bullous; Sitagliptin Phosphate; Vildagliptin
PubMed: 31215644
DOI: 10.1111/ajd.13100 -
Journal of Clinical Medicine May 2023The use of integrase inhibitor-based antiretroviral therapy could be associated with worse weight and metabolic outcomes in patients with HIV infection. (Review)
Review
BACKGROUND
The use of integrase inhibitor-based antiretroviral therapy could be associated with worse weight and metabolic outcomes in patients with HIV infection.
METHODS
PubMed, EMBASE, and Scopus were searched from inception to March 2022. We selected randomized controlled trials (RCTs) comparing integrase inhibitors with other antiretroviral classes (efavirenz-based or protease inhibitor-based therapies) in naïve HIV patients. Random effects meta-analysis was used to assess the effects of integrase inhibitors vs. controls on weight and lipid outcomes. Effects were described as mean differences (MD) and their 95% confidence intervals (CI). Certain pieces of evidence (CoE) were evaluated using the GRADE methodology.
RESULTS
Six RCTs (n = 3521) were included, with patients followed up between 48 and 96 weeks. The use of integrase inhibitors in comparison with other antiretroviral classes was associated with an increase in weight (MD 2.15 kg, 95%CI 1.40 to 2.90, I = 0%, moderate CoE), and decreases in total cholesterol (MD -13.44 mg/dL, 95%CI -23.49 to -3.39, I = 96%, low CoE), LDL cholesterol (MD -1.37 mg/dL, 95%CI -19.24 to -3.50, I = 83%, low CoE), HDL cholesterol (MD -5.03 mg/dL, 95%CI -10.61 to 0.54, I = 95%, low CoE), and triglycerides (MD -20.70 mg/dL, 95%CI -37.25 to -4.15, I = 92%, low CoE). There was a high risk of bias in two RCTs and some concerns about bias in two RCTs.
CONCLUSIONS
In HIV patients, the use of integrase inhibitor-based therapy in comparison with protease inhibitor- or NNRTI-based therapy was associated with a small increase in weight and small decreases in lipid serum levels.
PubMed: 37297839
DOI: 10.3390/jcm12113644