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Critical Care (London, England) Jul 2024Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency,... (Review)
Review
BACKGROUND
Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach.
METHODS
In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation.
RESULTS
A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes.
CONCLUSIONS
Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation.
IMPACT RESEARCH
To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.
Topics: Humans; Critical Illness; Vitamin K; Vitamin K Deficiency; Intensive Care Units
PubMed: 38956732
DOI: 10.1186/s13054-024-05001-2 -
Open Heart Jul 2024The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once...
BACKGROUND
The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry.
METHODS
Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA.
RESULTS
Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs.
CONCLUSION
Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.
Topics: Humans; Atrial Fibrillation; Factor Xa Inhibitors; Patient Selection; Stroke; Pyrazoles; Pyridones; Rivaroxaban; Male; Female; Aged; Treatment Outcome; Registries; Administration, Oral; Risk Factors; Randomized Controlled Trials as Topic; Risk Assessment; Anticoagulants; Vitamin K
PubMed: 38955399
DOI: 10.1136/openhrt-2024-002708 -
Pakistan Journal of Medical Sciences Jul 2024Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ... (Review)
Review
OBJECTIVE
Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ transplants.
METHODS
PubMed, Embase, and Web of Science libraries were searched from inception to 25 November 2023 for all studies comparing DOAC with VKA in solid organ recipients.
RESULTS
Nine studies were included with patients who had undergone kidney, heart, or liver transplants. Meta-analysis showed that patients receiving DOAC had a significantly reduced risk of composite bleeding as compared to those with VKA (RR: 0.45 95% CI: 0.30, 0.68 I=25%). However, the risk of major bleeding was not significantly different between the two groups (RR: 0.76 95% CI: 0.40, 1.42 I=37%). Pooled analysis showed that the risk of VTE (RR: 0.90 95% CI: 0.72, 1.13 I=0%) and ischemic stroke (RR: 0.87 95% CI: 0.39, 1.94 I=12%) was not significantly different between DOAC and VKA groups.
CONCLUSION
Limited data shows that DOAC are safe and effective in patients with solid organ transplants. The overall risk of bleeding may be reduced with the use of DOAC. There is a need for randomized controlled trials comparing DOAC and VKA in such patients to obtain high-quality evidence.
PubMed: 38952515
DOI: 10.12669/pjms.40.6.9305 -
Clinical Transplantation Jul 2024We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving... (Observational Study)
Observational Study
BACKGROUND
We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy.
METHODS
A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events.
RESULTS
Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%).
CONCLUSIONS
In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Platelet Aggregation Inhibitors; Anticoagulants; Follow-Up Studies; Heart Transplantation; Prognosis; Blood Transfusion; Risk Factors; Aged; Adult; Dabigatran; Postoperative Complications
PubMed: 38952201
DOI: 10.1111/ctr.15380 -
Cureus May 2024Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly... (Review)
Review
Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.
PubMed: 38947715
DOI: 10.7759/cureus.61374 -
Pulmonary Circulation Apr 2024Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical...
Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.
PubMed: 38947169
DOI: 10.1002/pul2.12406 -
Journal of Thrombosis and Haemostasis :... Jul 2024
Topics: Humans; Vitamin K; Perioperative Care; Anticoagulants; Blood Coagulation
PubMed: 38945667
DOI: 10.1016/j.jtha.2024.04.012 -
Revista Portuguesa de Cardiologia :... Jun 2024Oral anticoagulation (OAC) with non-vitamin K antagonist oral anticoagulants (NOACs) after surgical mitral valve repair (MVR) or bioprosthetic valve replacement (BVR) in...
INTRODUCTION AND OBJECTIVES
Oral anticoagulation (OAC) with non-vitamin K antagonist oral anticoagulants (NOACs) after surgical mitral valve repair (MVR) or bioprosthetic valve replacement (BVR) in mitral position remains a controversial topic among the cardiovascular community, in particular in the early postoperative period. This study aimed to evaluate the efficacy and safety of NOACs in the first three months after MVR or mitral BVR compared to vitamin K antagonists (VKAs).
METHODS
This was a single-center retrospective study with prospectively collected peri-intervention outcomes between 2020 and 2021. Records were retrieved and all participants were contacted by telephone. Patients were divided into groups according to OAC strategy. The primary outcome was a composite of death, rehospitalization, myocardial infarction, stroke or transient ischemic attack, systemic embolism, mitral thrombosis, or bleeding during the first three months after surgery.
RESULTS
A total of 148 patients were enrolled, with a mean age of 65.5±12.2 years, 56.8% male. On discharge, 98 (66.2%) patients were on VKAs and 50 (33.8%) were on DOACs for at least three months. The primary outcome occurred in 22 (22.4%) patients in the VKA group and in three (6%) in the NOAC group (p=0.012), mainly driven by more bleeding events in the former. Independent predictors of the primary outcome were smoking (p=0.028) and OAC with VKAs at discharge, the latter predicting three times more events (p=0.046, OR 3.72, 95% CI 1.02-13.5).
CONCLUSIONS
NOACs were associated with fewer events, supporting their efficacy and safety during the first three months after surgical MVR or mitral BVR.
PubMed: 38945474
DOI: 10.1016/j.repc.2024.02.013 -
Internal and Emergency Medicine Jun 2024It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation...
It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15-29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.
PubMed: 38943034
DOI: 10.1007/s11739-024-03658-9 -
JACC. Advances Apr 2024Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K...
BACKGROUND
Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants.
OBJECTIVES
To determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients.
METHODS
This is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years.
RESULTS
Of the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHADS-VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes.
CONCLUSIONS
WRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.
PubMed: 38939675
DOI: 10.1016/j.jacadv.2024.100880