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1.
Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis
Alwakeal, A., Maas, M. B., Naidech, A. M., Jahromi, B. S., Potts, M. B.
Critical care medicine. 2024
Abstract
OBJECTIVES Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. DATA SOURCES A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. STUDY SELECTION Abstracts and full texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. CONCLUSIONS A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.
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2.
Efficacy and safety of platelet-rich plasma in the treatment of venous ulcers: A systematic review and meta-analysis of randomized controlled trials
Hu, Z., Wang, S., Yang, H., Xv, H., Shan, B., Lin, L., Han, X.
International wound journal. 2024;21(2):e14736
Abstract
Considering the substantial impact of venous ulcers on quality of life and healthcare systems, this study evaluated the efficacy and safety of platelet-rich plasma (PRP) in comparison to conventional therapy. A systematic review of four databases identified 16 randomized clinical trials, including 20 study groups. PRP significantly enhanced complete ulcer healing, exhibiting an odds ratio (OR) of 5.06 (95% confidence interval [CI]: 2.35-10.89), and increased the percentage of healed ulcer area by a mean difference of 47% (95% CI: 32%-62%). Additionally, PRP shortened the time required for complete healing by an average of 3.25 months (95% CI: -4.06 to -2.43). Although pain reduction was similar in both groups, PRP considerably decreased ulcer recurrence rates (OR = 0.16, 95% CI: 0.05-0.50) without increasing the risks of infection or irritative dermatitis. These results suggest PRP as a viable, safe alternative for venous ulcer treatment, providing significant improvements in healing outcomes.
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3.
Endoscopic Primary Prophylaxis to Prevent Bleeding in Children with Esophageal Varices: A Systematic Review and Meta-Analysis
Alatas, F. S., Monica, E., Ongko, L., Kadim, M.
Pediatric gastroenterology, hepatology & nutrition. 2023;26(5):231-238
Abstract
PURPOSE This systematic review and meta-analysis aimed to compare endoscopy as primary versus secondary prophylaxis to prevent future bleeding in children with esophageal varices. METHODS A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was conducted using the Scopus, PubMed, and Cochrane databases for relevant studies on the outcome of rebleeding events after endoscopy in primary prophylaxis compared to that in secondary prophylaxis. The following keywords were used: esophageal varices, children, endoscopy, primary prophylaxis and bleeding. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale and statistically analyzed using RevMan 5.4 software. RESULTS A total of 174 children were included from four eligible articles. All four studies were considered of high-quality based on the Newcastle-Ottawa Quality Assessment Scale. Patients who received primary prophylaxis had 79% lower odds of bleeding than those who received secondary prophylaxis (odds ratio, 0.21; 95% confidence interval [CI], 0.07-0.66; I(2)=0%, p=0.008). Patients in the primary prophylaxis group underwent fewer endoscopic procedures to eradicate varices than those in the secondary prophylaxis group, with a mean difference of 1.73 (95% CI, 0.91-2.56; I(2)=62%, p<0.0001). CONCLUSION Children with high-risk varices who underwent primary prophylaxis were less likely to experience future bleeding episodes and required fewer endoscopic procedures to eradicate the varices than children who underwent secondary prophylaxis.
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4.
Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis
Vukadinović D, Abdin A, Emrich I, Schulze PC, von Haehling S, Böhm M
Clinical research in cardiology : official journal of the German Cardiac Society. 2023;:1-13
Abstract
INTRODUCTION AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. MATERIAL AND METHODS We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. RESULTS FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I(2) = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I(2) = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I(2) = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I(2) = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I(2) = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I(2) = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I(2) = 30%) were comparable between groups. There was no relevant heterogeneity (I(2) > 50%) between the trials for any of the analyzed outcomes. CONCLUSIONS Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while effects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.
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5.
Treating Iron Deficiency (ID) Anemia in Heart Failure (HF) Patients with IV Iron: A Meta-Analysis
Ogugua, F. M., Aguilar, F. A., Gamam, A., Maqsood, M. H., Yoo, T. K., Kasmi, F., AlKowatli, O., Lo, K.
Cureus. 2023;15(7):e41895
Abstract
Findings on the effects of iron on heart failure (HF) hospitalizations and mortality among patients with iron deficiency (ID) and HF remain conflicting across different studies. We performed a meta-analysis of clinical trials assessing the clinical, hematic and cardiovascular benefits of treating ID in HF patients. We completed a systematic search for studies comparing IV iron to placebo in HF patients with ID. The primary outcomes were rates of HF hospitalization and all-cause mortality. Secondary outcomes included change in hematic values, New York Heart Association (NYHA) class and ejection fraction. We applied a random-effects model with planned sensitivity analyses of studies with skewed effect sizes. Nine studies were included with a total of 2,261 patients. Analysis revealed that treatment of HF patients with IV iron replacement significantly reduced the odds of HF hospitalization (odds ratio (OR): 0.44; 95% confidence interval (CI): 0.24 to 0.78; p=0.005, I(2)=67%),) but did not significantly impact all-cause mortality compared to placebo (OR: 0.89; 95%, CI: 0.67 to 1.19; p=0.44, I(2): 0%). Analysis showed that IV iron treatment group had significantly higher serum ferritin, transferrin saturation and hemoglobin (Hb) levels. They also had lower NYHA class -1.90 (95% CI (-2.91 to -0.89); p<0.001, I(2):89%) with higher ejection fraction 0.50 (95% CI (0.09 to 0.90) p=0.016, I(2):86%). Treatment with IV iron in HF patients with ID is associated with a significant reduction of HF hospitalization but no effects on all-cause mortality. There were also significant increases in hematic values and ejection fraction with a reduction in NYHA class.
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6.
Effect of Intravenous Iron-Carbohydrate Complexes in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: A Meta-analysis of Randomized Controlled Trials
Mototani R, Watanabe A, Kuno T, Briasoulis A
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese. 2023
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7.
Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction
Hamza, M., Sattar, Y., Manasrah, N., Patel, N. N., Rashdi, A., Khanal, R., Naveed, H., Zafar, M., Khan, A. M., Alharbi, A., et al
The American journal of cardiology. 2023;202:119-130
Abstract
Iron deficiency is an independent risk factor for heart failure (HF) exacerbation. We aim to study the safety and efficacy of intravenous (IV) iron therapy in patients with HF with reduced ejection fraction (HFrEF). A literature search was conducted on MEDLINE (Embase and PubMed) using a systematic search strategy by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) until October 2022. CRAN-R software (The R Foundation for Statistical Computing, Vienna, Austria) was used for statistical analysis. The quality assessment was performed using the Cochrane Risk of Bias and Newcastle-Ottawa Scale. We included 12 studies with a total of 4,376 patients (IV iron n = 1,985 [45.3%]; standard of care [SOC] n = 2,391 [54.6%]). The mean age was 70.37 ± 8.14 years and 71.75 ± 7.01 years in the IV iron and SOC groups, respectively. There was no significant difference in all-cause mortality and cardiovascular mortality (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.74 to 1.04, p <0.15). However, HF readmissions were significantly lower in the IV iron group (RR 0.73, 95% CI 0.56 to 0.96, p = 0.026). Non-HF cardiac readmissions were not significantly different between the IV iron and SOC groups (RR 0.92, 95% CI 0.82 to 1.02, p = 0.12). In terms of safety, there was a similar rate of infection-related adverse events in both arms (RR 0.86, 95% CI 0.74 to 1, p = 0.05). IV iron therapy in patients with HFrEF is safe and shows a significant reduction in HF hospitalizations compared with SOC. There was no difference in the rate of infection-related adverse events. The changing landscape of HFrEF pharmacotherapy in the last decade may warrant a re-demonstration of the benefit of IV iron with current SOC. The cost-effectiveness of IV iron use also needs further study.
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8.
Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials
Hamed, M., Elseidy, S. A., Ahmed, A., Thakker, R., Mansoor, H., Khalili, H., Mohsen, A., Mamas, M. A., Banerjee, S., Kumbhani, D. J., et al
Heliyon. 2023;9(6):e17245
Abstract
BACKGROUND Randomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results. METHODS Electronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model. RESULTS The final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59-0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57-0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75-1.04) and all-cause mortality (RR 0.95; 95% CI 0.83-1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF. CONCLUSION Among patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.
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9.
Clinical outcomes of intravenous Iron therapy in patients with heart failure and Iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials
Bhatia, K., Sabharwal, B., Gupta, K., Lopez, P. D., Kaur, A., Bhatia, H. K., Gandhi, K. D., Niroula, S., Correa, A., Birati, E. Y., et al
Journal of cardiology. 2023
Abstract
BACKGROUND Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I(2) = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I(2) = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.
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10.
Intravenous Iron for Heart Failure: Updated Systematic Review and Meta-Analysis
Techasatian, W., Nishimura, Y., Tanariyakul, M., Morihara, C., Arayangkool, C., Settle, A., Aiumtrakul, N., Kewcharoen, J.
Angiology. 2023;:33197231213181
Abstract
While the administration of intravenous (IV) iron to those with heart failure has been implicated to be associated with a possible reduction in hospitalizations and improvement in symptoms, a recent large multicenter trial only showed modest benefits in reducing hospitalization, necessitating the updated systematic review. We conducted a systematic review and meta-analysis, searching the MEDLINE and EMBASE database until January 9, 2023. Outcomes included total heart failure hospitalizations, first heart failure hospitalization, six-minute walk test (6MWT) distance, and incidence of infection. There were 13 studies with 3410 participants (1,790 with IV iron). Pooled analysis that reported the incidence of cardiovascular death showed that patients with IV iron did not have significantly lower odds of cardiovascular death or first heart failure hospitalization. In contrast, those who received IV iron had significantly lower total heart failure hospitalization (pooled odds ratio (OR) 0.63, 95% confidence interval (CI) 0.44-0.90, I(2) 59.0%, P = .017) and a composite of cardiovascular death and first heart failure hospitalization (pooled OR 0.55, 95% CI 0.47-0.64, I(2) 0%, P = .656). While the efficacy is modest, IV iron therapy could be associated with reduced hospitalization for heart failure without significant adverse events.