Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. METHODS: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. RESULTS: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. CONCLUSIONS: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered on the PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD498330.

Skeletonized versus Pedicled harvesting of internal mammary artery: A systematic review and Meta-analysis.

There are two recognized internal mammary artery (IMA) harvesting techniques during coronary artery bypass grafting (CABG): pedicled and skeletonized. This systematic review and meta-analysis sought to compare the clinical outcomes of the two harvesting techniques. A comprehensive electronic literature search of PubMed, Scopus, and Embase was conducted from inception till June 2023. Thirty-one studies with a total of 13005 patients met our inclusion criteria. The results from the included studies were presented as weighted mean difference (WMD) with its relevant standard deviation (SD) for continuous variables, while Odds Ratio (OR) was used for dichotomous variables. A 95% confidence interval (CI) was used, and the results were pooled using a random effects model. The skeletonized IMA demonstrated a significantly reduced risk of sternal wound infection (SWI) compared to the pedicled IMA (OR = 0.45 [95% CI, 0.32-0.66]; p = 0.0001). The conduit length used was significantly longer in the skeletonized IMA (WMD -2.48, 95% CI, [-3.75, -1.20], P = 0.0001) and a significantly higher postoperative flow rate was observed while using skeletonization compared to the pedicled harvesting (WMD -13.11, 95% CI, [-22.52, -3.70], P = 0.006). However, no significant difference was seen in mortality between the two techniques (OR = 1.19 [95% CI, 1.00-1.41]; p = 0.05). Pedicled harvesting demonstrated significantly reduced incidents of MI (OR = 1.38 [95% CI, 1.13-1.69]; p = 0.002), while significant results in graft patency were observed favoring pedicled harvesting over skeletonization (OR = 0.63 [95% CI, 0.40-0.98]; p = 0.04).

Cardiovascular and Cerebrovascular Outcomes With Vitamin D Supplementation: A Systematic Review and Meta-Analysis.

Vitamin D supplementation has seen a sharp increase in the primary healthcare setting but its efficacy in decreasing the risk of cardiovascular and cerebrovascular events is yet to be reliably established. We aim to determine whether vitamin D supplementation can significantly impact the risk of cardiovascular and cerebrovascular events. An extensive literature search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception till August 2023 to include all the articles comparing vitamin D and placebo. Cardiovascular and cerebrovascular outcomes were presented as risk ratios (RR) with 95% confidence intervals (CIs) and pooled using a random effects model. Thirty-six trials consisting of 493,389 participants were included in our analysis. Our pooled analysis demonstrated no significant difference between vitamin D supplementation and placebo for the risk of cardiovascular mortality (RR 1.01, 95% CI 0.94-1.08; P = 0.80), stroke or cerebrovascular events (RR 1.03, 95% CI 0.95-1.11; P = 0.48), myocardial infarction (MI) (RR 0.98, 95% CI 0.91-1.06; P = 0.65), cerebrovascular mortality (RR 1.00, 95% CI 0.68-1.46; P = 0.99), arrhythmias (RR 0.98, 95% CI 0.66-1.44; P = 0.90) and hemorrhagic or ischemic stroke. There was no significant heterogeneity between the studies in any analysis. There was no significant difference in the risk of cardiovascular and cerebrovascular outcomes with vitamin D supplementation or placebo. Additional large high-powered studies focused on high-risk and vitamin D-deficient populations are required to resolve the current discrepancy in the literature and provide a definitive conclusion to this end.

Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

BACKGROUND: The effect of sacubitril/valsartan on patients with heart failure (HF) with preserved ejection fraction (HFpEF) is a topic of ongoing debate. METHODS: Medline was queried from inception through the last week of May 2023 for randomized studies assessing the effects of sacubitril/valsartan in patients with HFpEF. For continuous outcomes, we pooled either the geometric mean ratios (gMR) or weighted mean difference (WMD) with 95% confidence intervals (CI). For dichotomous outcomes, we pooled Risk ratios (RR) with 95% CI. RESULTS: Four trials were included (N=8,129). Compared to the control, sacubitril/valsartan was associated with a reduction in NT-proBNP levels (gMR: 0.84, 95% CI 0.80, 0.88) and improvement in KCCQ score (WMD: 0.85, 95% CI: 0.02, 1.67). We observed no differences for HF hospitalization (RR: 0.90, 95% CI: 0.79, 1.01), cardiovascular mortality (RR: 0.83, 95% CI: 0.52, 1.32), all-cause mortality (RR: 0.99, 95% CI: 0.86-1.13) and improvement (RR: 1.15, 95% CI: 0.93, 1.42) or worsening (RR: 0.92, 95% CI: 0.78, 1.09) of NYHA class between the sacubitril/valsartan and comparator group. Sacubitril/valsartan was generally safe, and patients were less likely to have a ≥50% decline in eGFR compared to control (RR: 0.60, 95% CI: 0.39, 0.92). CONCLUSION: Pooled analysis suggests that sacubitril/valsartan reduces natriuretic peptide levels and improves the quality of life in patients with HFpEF, which may translate into better clinical outcomes as observed by a numerical trend towards improvement in major HF outcomes with sacubitril/valsartan therapy.

Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Limited data comparing prasugrel and ticagrelor in acute coronary syndrome are available. Online databases, including MEDLINE and Cochrane Central, were queried to compare these drugs. The primary outcomes of this meta-analysis are myocardial infarction (MI), all-cause mortality, cardiovascular mortality, noncardiovascular mortality, stent thrombosis, and stroke. The secondary outcome is major bleeding. A total of 9 studies, including 94,590 patients (prasugrel group = 32,759; ticagrelor group = 61,831), were included in this meta-analysis. The overall mean age was 62.73 years, whereas the mean age for the ticagrelor and prasugrel groups was 63.80 and 61.65 years, respectively. Prasugrel is equally effective as compared with ticagrelor in preventing MI. There was no difference between the 2 groups regarding all-cause mortality, stent thrombosis, stroke, or major bleeding. In patients with acute coronary syndrome, prasugrel is equally effective when compared with ticagrelor in preventing MI.

Cerebrovascular disease in COVID-19: a systematic review and meta-analysis.

Background: The association between COVID-19 and acute cerebrovascular disease (CVD) has not been explored extensively. New data has come to light which may change previous results. Methods: We queried the PubMed electronic database from its inception until February 2022 for studies evaluating the incidence of stroke in COVID-19 patients. Results of the analysis were pooled using a random-effects model and presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: 37 studies consisting of 294,249 patients were included in our analysis. Pooled results show that the incidence of acute CVD events in COVID-19 positive patients is 2.6% (95% CI: 2.0-3.3; P<0.001). Cardioembolic (OR=14.15, 95% CI: 11.01 to 18.19, P<0.00001) and cryptogenic (OR=2.87, 95% CI: 1.91 to 4.32, P<0.00001) etiologies were associated with COVID-19 positivity. Risk factors for CVD events in patients with COVID-19 were atrial fibrillation (OR=2.60, 95% CI: 1.15 to 5.87, P=0.02), coronary artery disease (OR=2.24, 95% CI: 1.38 to 3.61, P=0.0010), diabetes (OR=2.46, 95% CI: 1.36 to 4.44, P=0.003) and hypertension (OR=3.65, 95% CI: 1.69 to 7.90, P=0.005). Conclusion: COVID-19 infection is associated with an increased risk for acute CVD and is associated with cardioembolic and cryptogenic etiologies and the risk factors of atrial fibrillation, coronary artery disease, diabetes and hypertension in COVID-19 positive patients.

The association of antibiotic exposure with new-onset inflammatory bowel disease: A systematic review and meta-analysis.

INTRODUCTION: The role of antibiotics in the development of inflammatory bowel disease (IBD) remains controversial, primarily due to conflicting data from individual studies. We conduct a systematic review and meta-analysis to study the effect of antibiotic exposure on IBD development. METHODOLOGY: The MEDLINE and Cochrane CENTRAL databases were queried from their inception to April 2021 for published articles studying the association between antibiotic exposure and new-onset IBD. Our analysis was stratified by timing of antibiotic exposure - exposure in childhood and any lifetime exposure. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from each study were pooled using a random-effects model. RESULTS: 10 case-control studies and 2 cohort studies (N = 29,880 IBD patients and N = 715,548 controls) were included. Patients with Crohn's Disease (CD), compared with controls, were associated significantly with antibiotic exposure in childhood and any lifetime exposure to antibiotics (OR 1.52 [1.23-1.87]; p<0.00001). Patients with Ulcerative Colitis (UC), compared with controls, reported non-significant association with antibiotic exposure in childhood and any lifetime exposure. (OR 1.11 [0.93-1.33]; p = 0.25) CONCLUSION: This meta-analysis suggests that exposure to antibiotics significantly increases the odds of developing CD and IBD. These findings re-emphasize the importance of cautious and judicious use of antibiotics.

Evaluating the safety and efficacy of daprodustat for anemia of chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia of chronic kidney disease (CKD) has traditionally been treated with recombinant human erythropoietin (rhEPO). Recently, daprodustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, has also been shown to increase hematocrit. It remains unclear whether daprodustat or rhEPO should be the treatment of choice for anemia of CKD. We aimed to assess the efficacy and cardiovascular safety of daprodustat versus rhEPO in CKD patients. METHODS: Online databases were queried in April 2022 for articles comparing the efficacy and safety of daprodustat in DD-CKD and NDD-CKD subgroups. Results from trials were pooled using a random-effects model. RESULTS: Data on 8245 CKD patients from eight clinical trials were included. Our results show that in comparison to rhEPO, daprodustat maintained the same efficacy in increasing hemoglobin levels in both the DD-CKD (MD: 0.10; 95% CI [- 0.13,0.34]; p = 0.50) and NDD-CKD (MD: - 0.01; 95% CI [- 0.38,0.35]; p = 0.95) subgroups. Daprodustat significantly lowered hepcidin levels and significantly increased TIBC in both subgroups. Additionally, daprodustat significantly reduced the incidence of major adverse cardiovascular events (MACE) (RR: 0.89; 95% CI: 0.89-0.98; p = 0.02) and its myocardial infarction (MI) component (RR: 0.74; 95% CI: 0.59-0.92; p = 0.006) in the DD-CKD subgroup. CONCLUSION: Daprodustat has similar efficacy compared to rhEPO for the treatment of anemia of CKD. On treatment, the reduced experience of MACE was reported in DD-CKD patients as compared to rhEPO. Furthermore, effects on iron metabolism varied by parameter, with daprodustat being superior to rhEPO in some cases and inferior in others.

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear. AIM: To conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis). METHODS: MEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs). RESULTS: Our pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87). CONCLUSION: SGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.