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1.
Economic evaluation of ferric carboxymaltose compared with placebo in iron-deficient patients with heart failure: a systematic review
Rezapour A, Souresrafil A, Shamsaei M, Barzegar M, Tashakori-Miyanroudi M, Ketabchi E
International journal of clinical pharmacy. 2023
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Editor's Choice
Abstract
BACKGROUND It has been shown that ferric carboxymaltose (FCM) improves symptoms and quality of life in iron-deficient patients with heart failure (HF). AIM: We aimed to systematically review studies conducted on the cost-effectiveness of FCM compared to placebo in iron-deficient patients with HF. METHOD We searched PubMed, EMBASE, Scopus, and Web of Science to find the relevant studies. After removing duplicates, two authors independently evaluated the titles, abstracts, and full texts. We included studies that investigated the full economic evaluations of FCM in HF patients with iron deficiency (cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis) and used the CHEERS tool to evaluate the quality of the studies. RESULTS Seven studies were included which evaluated the economic analysis of treatments with FCM in iron-deficient patients with HF. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF. CONCLUSION FCM is a cost-effective treatment for iron-deficient patients with HF. Considering the fact that all the included studies in the present systematic review took place in high-income countries, we recommend further studies investigating the cost-effectiveness of FCM in low- and middle-income countries.
PICO Summary
Population
Iron-deficient patients with heart failure (HF), (7 studies).
Intervention
Ferric carboxymaltose (FCM).
Comparison
Placebo.
Outcome
The included studies investigated cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis, and used the CHEERS tool to evaluate the quality of the studies. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1,801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF.
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Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalisation: A European multinational economic evaluation
McEwan P, Harrison C, Binnie R, Lewis RD, Cohen-Solal A, Lund LH, Ohlsson M, von Haehling S, Comin-Colet J, Pascual-Figal DA, et al
European journal of heart failure. 2023
Abstract
AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalisations and improved quality of life when used to treat ID at discharge in patients hospitalised for acute HF with left-ventricular ejection fraction of <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS The per country eligible population was calculated, aligning with the ESC 2021 HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalisation episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13,237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalisations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5,215 in Sweden to 205,630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within one year. CONCLUSIONS This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realised through implementation of the ESC HF guideline recommendations regarding ID treatment. This article is protected by copyright. All rights reserved.
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3.
Systematic review and meta-analysis of intravenous iron-carbohydrate complexes in HFrEF patients with iron deficiency
Sindone A, Doehner W, Comin-Colet J
ESC heart failure. 2022
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Free full text
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Editor's Choice
Abstract
Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.
PICO Summary
Population
Patients with heart failure (HF) with reduced ejection fraction (HFrEF) and iron deficiency, (12 randomised controlled trials, n= 2,381).
Intervention
Intravenous (IV) iron-carbohydrate complex supplementation.
Comparison
Placebo or standard of care.
Outcome
The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose; 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65)] and first hospitalization for worsening HF or death [0.75 (0.59-0.95)], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms.
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Randomized prospective comparative study of platelet-rich plasma versus conventional compression in treatment of post-phlebitic venous ulcer
Shehab AW, Eleshra A, Fouda E, Elwakeel H, Farag M
Vascular. 2022;:17085381221104629
Abstract
OBJECTIVES to assess the safety and efficacy of platelet-rich plasma (PRP) as adjunctive to compression therapy for post-phlebitic venous ulcers. METHODS This is a single-center randomized controlled trial on patients with persistent chronic post-phlebitic lower limb venous ulcers from March 2019 to March 2020. Patients were randomly allocated to one of two equal cohort groups. Patients group in which patients underwent combined PRP with compression therapy versus control group in which patients underwent placebo+ compression therapy alone. The primary endpoint of the study was the improvement in ulcer topographic measurement. Secondary endpoints included ulcer healing parameters, possible healing factors, reduction in pain score (VAS), and the achievement of complete healing. RESULTS Forty patients were available equally for randomization and analysis in both groups. The median number of PRP applications for every patient in the patient group was 6 (ranging from 3 to 6). There was a significant decline in the median length, width, and depth of ulcers in the patients group versus control group. Consequently, there was a significant decline of the median ulcer area, in the patient group versus control group (4 (3-9) cm(2) vs. 10 (6-14) cm(2), p = .036). Also, the median volume of the ulcers showed a significant decline in the patient group versus control group (1 (.7-3) cm(3) vs 3 (2-6) cm(3), p = .008). Complete healing was achieved in 45% of patient group. There was a significant decline in pain scores at 3- and 6 months from the therapy starting point in both groups (patient group: pre-VAS = 6.5 vs. post(3 months)-VAS = 1 vs. post(6 months)-VAS = 0.5) and (control group: pre-VAS = 6.4 vs. post(3 months)-VAS = 4.5 vs. post(6 months)-VAS = 2.2), (p < .0001 for each). On the other hand, the decline in pain scores between both groups was statistically significant in favor of the patient group, (post (3 months); PRP-VAS = 1 vs. control-VAS = 4.5, and post(6 months); PRP-VAS = 0.5 vs. control-VAS = 2.2), (p < .0001). CONCLUSION Platelet-rich plasma as an adjunct to compression therapy for chronic post-phlebitic venous ulcers is safe and effective as regards the ulcer healing and improvement of pain score. PRP may be useful adjunct in treatment of post-phlebitic venous ulcer. However, larger trials are warranted.
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Safety of Vitamin K in mechanical heart valve patients with supratherapeutic INR: A systematic review and meta-analysis
Sapapsap B, Srisawat C, Suthumpoung P, Luengrungkiat O, Leelakanok N, Saokaew S, Kanchanasurakit S
Medicine. 2022;101(36):e30388
Abstract
BACKGROUND Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR. METHODS CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test. RESULTS From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively). CONCLUSION The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.
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IV Sodium Ferric Gluconate Complex in Patients with Iron Deficiency hospitalized due to Acute Heart Failure- Investigator initiated, Randomized controlled trial
Marcusohn E, Borreda I, Hellman Y, Habib M, Bahouth F, Epstein D, Zukermann R
Journal of cardiovascular pharmacology. 2022
Abstract
Heart failure (HF) patients with iron deficiency (ID) have worse NYHA class and are at a higher risk of recurrent hospitalizations. Intravenous (IV) iron has been shown to improve exercise ability and reduce hospitalizations. IV Sodium Ferric Gluconate Complex (SFGC) has been found to be safe and affordable but has not been studied in this population in a randomized trial. This was prospective, single-blind, investigator-initiated, randomized controlled trial. Patients admitted for acute heart failure with ID were randomly assigned 1:1 to receive IV SFGC on top of optimal medical treatment. The primary outcome was the change in 6-minute walk test (6MWT) from baseline to 3 and 6 months. Between September 2019 and May 2021, 34 patients were randomized. 19 patients (55%) were randomized to the treatment arm receiving 125 mg of IV SFGC per day for 3 to 5 days . COVID-19 was a major barrier to the implementation of the study follow-up protocol, which caused the study to end early. Both groups of patients had similar clinical characteristics, comorbidities, median LVEF, and rate of death and readmissions due to HF. A higher level of NT-proBNP was observed in patients treated with IV iron (7902 pg/ml vs 3158, p=0.04). There was no difference in 6MWT change between groups at 3 months (improvement of 21.6 vs 24.1 meters), or 6 months (-5 meters vs. 46 meters). In conclusion, IV SFGC treated patients had comparable 6-minute walk at 3 and 6 months despite suffering from more severe HF with higher baseline NT-Pro BNP. (NCT04063033).
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Bleeding Episodes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Very Early Versus Standard Care Invasive Examination (from the Very EaRly vs Deferred Invasive Evaluation Using Computerised Tomography [VERDICT] Trial)
Sadjadieh G, Kelbæk H, Kofoed KF, Køber LV, Hansen PR, Torp-Pedersen C, Elming H, Gislason G, Høfsten DE, Engstrøm T, et al
The American journal of cardiology. 2022
Abstract
Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72 hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30 days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p = 0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p = 0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p <0.001), and increasing blood pressure (HR 1.3, 95% CI 1.1 to 1.5; p = 0.01) were individually associated with serious bleeding, whereas GRACE score >140 was not (HR 1.03, 95% CI 0.4 to 2.9; p = 0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30 days, which was associated with female gender, increasing blood pressure, and anemia.
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Recent Advancements in the Management of Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Systematic Review
Arzoun H, Srinivasan M, Thangaraj SR, Thomas SS, Yarema A, Lee B, Mohammed L
Cureus. 2022;14(2):e21814
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood vessels and is more commonly seen in the geriatric population. ANCA-associated vasculitis (AAV) is typically characterized as necrotizing vasculitis and includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The mortality rate remains high, with especially cardiovascular disease, infections, and malignancies being the leading causes of death. Existing treatment options depend heavily on the use of glucocorticoids (GCs), often in combination with cyclophosphamide (CYC); however, as the multitude of adverse effects associated with these agents has increased, numerous studies are being conducted to reduce not only these harmful effects but also improve remission rates. Rituximab, avacopan, corticosteroids, including intravenous pulse methylprednisolone, plasma exchange, and immunological targeting are among the emerging treatments. The purpose of this review is to emphasize the pathogenesis and traditional treatment modalities and give insights into the recent advances in managing this disorder in an attempt to spare the adverse effects of conventional therapies while achieving better remission rates with combination therapies as well. The authors explored multiple databases, employing appropriate keywords, satisfying the quality appraisal, after which a total of 14 reports were included in this review. Upon overall analysis, it can be concluded that rituximab and CYC, when used in combination, provided a safer alternative to GCs while exhibiting equal, if not superior, effectiveness and results, thus, paving the way for additional in-depth research in a larger population of interest.
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Health Status Improvement with Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency
Butler J, Khan MS, Friede T, Jankowska EA, Fabien V, Goehring UM, Dorigotti F, Metra M, Piña IL, Coats AJ, et al
European journal of heart failure. 2022
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Abstract
AIM: Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM vs placebo and evaluated the stability of this response over time. METHODS Changes vs baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups . Mean between-group differences were estimated and individual responder analyses and analyses of response stability were performed. RESULTS Overall, 760 (FCM: 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM vs 4.8 points with placebo (least-square mean difference [95% confidence interval (CI)]: 4.36 [2.14;6.59] points). A higher proportion of patients on FCM vs placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs 43.5%; odds ratio [95% CI]: 1.81 [1.30;2.51]), ≥10 (42.4% vs 29.3%; 1.73 [1.23;2.43]) or ≥15 (32.1% vs 22.6%; 1.46 [1.02;2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5-, ≥10- or ≥15-point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24. CONCLUSION Treatment of iron-deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual-patient level; benefits were sustained over time in most patients. This article is protected by copyright. All rights reserved.
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10.
Comparison of multiple treatments in the management of transplant-related thrombotic microangiopathy: a network meta-analysis
Yang J, Xu X, Han S, Qi J, Li X, Pan T, Zhang R, Han Y
Annals of hematology. 2022
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Editor's Choice
Abstract
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA.
PICO Summary
Population
Patients receiving treatment for transplantation-associated thrombotic microangiopathy (TA-TMA), (6 studies, n= 71).
Intervention
Therapeutic plasma exchange (TPE).
Comparison
Recombinant human soluble thrombomodulin (rTM). Eculizumab. Immunosuppression manipulation (ISM). Supportive care.
Outcome
There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities showed that rTM was most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM rank 3 (32.24%), intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM had significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE had lower efficacy than all other TA-TMA therapies exception to supportive care.
