Guidelines recommend that intravenous iron should be considered to improve symptoms of heart failure (HF) and reduce the risk for HF admissions in patients after acute HF.

This study sought to analyze the effect of intravenous iron on cardiovascular (CV) death and HF admissions in a broad population of HF patients with iron deficiency and the relation with baseline transferrin saturation (TSAT).

A systematic review of all published randomized controlled trials assessing the effect of intravenous iron in patients with iron deficiency and HF between January 1, 2000, and August 26, 2023, was performed. The overall treatment effect was estimated using a fixed effect model for: 1) CV death; 2) CV death and HF admission; 3) first HF admission; and 4) total HF admissions. Metaregression through a mixed effect model was used to explore the impact of baseline TSAT in case of heterogeneity among trial results.

A total of 14 randomized controlled trials were identified in the systematic review and retained in the meta-analysis. Aggregate-level data were included on 6,624 HF patients, 3,407 of whom were randomized to intravenous iron and 3,217 to placebo. Treatment with intravenous iron resulted in a lower risk for CV death (OR: 0.867 [95% CI: 0.755-0.955]; P = 0.0427), combined CV death and HF admission (OR: 0.838 [95% CI: 0.751-0.936]; P = 0.0015), first HF admission (OR: 0.855 [95% CI: 0.744-0.983]; P = 0.0281), and total HF admissions (rate ratio: 0.739 [95% CI: 0.661-0.827]; P < 0.0001). Significant heterogeneity among trial results was observed for first and total HF admissions. Metaregression suggested that some of the heterogeneity was related to the baseline TSAT of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events.

The totality of data suggests that treatment with intravenous iron reduces both CV death and HF-related events in a broad population with HF. A lower baseline TSAT might be important for the effect on HF-related events.

We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.

Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia.

We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted.

Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting.

This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS.

PROSPERO CRD42020214247.

Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) are a novel group of drugs used to treat renal anemia, but their benefits vary among different trials. Our meta-analysis aims to assess the safety and efficacy of HIF-PHI versus erythropoiesis-stimulating agents (ESA) in managing anemia among patients with chronic kidney disease (CKD), regardless of their dialysis status. PubMed, Embase, and Google Scholar were queried to discover eligible randomized controlled trials (RCTs). To quantify the specific effects of HIF-PHI, we estimated pooled mean differences (MDs) and relative risks (RR) with 95% CIs. Our meta-analysis involved 22,151 CKD patients, with 11,234 receiving HIF-PHI and 10,917 receiving ESA from 19 different RCTs. The HIF-PHI used included roxadustat, daprodustat, and vadadustat. HIF-PHI yielded a slight but significant increase in change in mean hemoglobin (Hb) levels (MD: 0.06, 95% CI (0.00, 0.11); p = 0.03), with the maximum significant increase shown in roxadustat followed by daprodustat as compared to ESA. There was a significant decrease in efficacy outcomes such as change in mean iron (MD: -1.54, 95% CI (-3.01, -0.06); p = 0.04), change in mean hepcidin (MD: -21.04, 95% CI (-28.92, -13.17); p < 0.00001), change in mean ferritin (MD: -16.45, 95% CI (-27.17,-5.73); p = 0.03) with roxadustat showing maximum efficacy followed by daprodustat. As for safety, HIF-PHI showed significantly increased incidence in safety outcomes such as diarrhea (MD: 1.3, 95% CI (1.11, 1.51); p = 0.001), adverse events leading to withdrawal (MD: 2.03, 95% CI (1.5, 2.74), p = 0.00001) among 25 various analyzed outcomes. This meta-analysis indicates that HIF-PHIs present a potentially safer and more effective alternative to ESAs, with increased Hb levels and decreased iron usage in CKD patients without significantly increasing adverse events. Therefore, in these patients, we propose HIF-PHI alongside renal anemia treatment.

Bleeding remains a common complication post-thoracic surgery. Although intravenous tranexamic acid (TXA) has been shown to decrease blood loss, its use has been associated with adverse effects. Accordingly, topical TXA has been proposed as an alternative to reduce bleeding with fewer systemic complications.

We searched Medline, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing topical TXA versus control (i.e., placebo) in patients undergoing thoracic procedures. The primary outcome was total postoperative blood loss at 24 hours. Secondary outcomes included were the number of red blood cell (RBC) transfusions, and hospital length of stay (LOS). Meta-analyses were pooled using mean difference with inverse-variance weighting and random-effects.

Out of the 575 unique studies that were screened, we identified three randomized controlled trials (RCTs) involving 399 patients. Out of the three RCTs analyzed, two studies, accounting for 67% of the total, were found to have a low risk of bias. The primary outcome of 24-h post-operative blood loss was significantly lower in patients who received TXA (mean difference [MD] -93.6 ml, 95% CI -121.8 to -65.4 ml, I2 = 45%). In addition, the need for RBC transfusion was significantly lower in the topical TXA group compared to control (MD -0.5 units, 95% CI -0.8 to -0.3 units, I2 = 60%). However, there was no significant difference in the hospital length of stay (LOS) (MD -0.3 days, 95% CI -0.9 to 0.4 days, I2 = 0%). These results remained consistent after several sensitivity analyses. The use of topical intrapleural tranexamic acid has also been found to be safe without any significant safety concerns.

Topical intrapleural TXA reduces blood loss and the need for blood transfusions during thoracic surgery. In addition, there is no evidence of the increased safety concerns associated with its use. Larger trials are necessary to validate these findings and evaluate the safety and efficacy of different dosages.

Hyperphosphatemia and anemia, which are common complications of chronic kidney disease (CKD), can independently contribute to cardiovascular events. Several previous studies have found that the iron-based phosphate binder, ferric citrate (FC), could be beneficial to both hyperphosphatemia and anemia.

Relevant literature from PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CCRCT) and MEDLINE databases were searched up to 21 February 2022, in order to conduct a meta-analysis to investigate the efficacy, safety and economic benefits of ferric citrate treatment in CKD patients with hyperphosphatemia and anemia. The meta-analysis was conducted independently by two reviewers using the RevMan software (version 5.3).

In total, this study included 16 randomized clinical trials (RCT) involving 1754 participants. The meta-analysis showed that ferric citrate could significantly reduce the serum phosphorus in CKD patients compared to the placebo control groups (MD -1.76 mg/dL, 95% CI (-2.78, -0.75); p = 0.0007). In contrast, the difference between ferric citrate treatment and active controls, such as non-iron-based phosphate binders, sevelamer, calcium carbonate, lanthanum carbonate and sodium ferrous citrate, was not statistically significant (MD - 0.09 mg/dL, 95% CI (-0.35, 0.17); p = 0.51). However, ferric citrate could effectively improve hemoglobin levels when compared to the active drug (MD 0.43 g/dL, 95% CI (0.04, 0.82); p = 0.03) and placebo groups (MD 0.39 g/dL, 95% CI (0.04, 0.73); p = 0.03). According to eight studies, ferric citrate was found to be cost-effective treatment in comparison to control drugs. Most of the adverse events (AE) following ferric citrate treatment were mild at most.

Collectively, our review suggests that iron-based phosphate binder, ferric citrate is an effective and safe treatment option for CKD patients with hyperphosphatemia and anemia. More importantly, this alternative treatment may also less expensive. Nevertheless, more scientific studies are warranted to validate our findings.