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Journal of Clinical Pharmacology Apr 2023Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when... (Review)
Review
Direct Oral Anticoagulants: An Updated Systematic Review of Their Clinical Pharmacology and Clinical Effectiveness and Safety in Patients With Nonvalvular Atrial Fibrillation.
Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.
Topics: Humans; Atrial Fibrillation; Stroke; Pharmacology, Clinical; Administration, Oral; Anticoagulants; Rivaroxaban; Treatment Outcome; Vitamin K; Dabigatran
PubMed: 36433678
DOI: 10.1002/jcph.2184 -
Clinical Nutrition ESPEN Oct 2022Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.
Topics: Arthritis, Rheumatoid; Gastrointestinal Microbiome; Humans; Inflammation; Probiotics; Rheumatic Fever; Vitamin K; Vitamins
PubMed: 36184230
DOI: 10.1016/j.clnesp.2022.08.002 -
Vitamin K antagonist reversal strategies: Systematic review and network meta-analysis from the AABB.Transfusion Aug 2022Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.
STUDY DESIGN AND METHODS
Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).
RESULTS
Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).
CONCLUSIONS
PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs.
Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Factor X; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Network Meta-Analysis; Prothrombin; Retrospective Studies; Vitamin K; Warfarin
PubMed: 35834523
DOI: 10.1111/trf.17010 -
JPMA. the Journal of the Pakistan... Nov 2022This systematic review and meta-analysis aims to estimate the prevalence of neonatal vitamin K prophylaxis refusal among parents and its possible association with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This systematic review and meta-analysis aims to estimate the prevalence of neonatal vitamin K prophylaxis refusal among parents and its possible association with subsequent vaccine hesitancy or refusal.
METHODS
The databases searched included PubMed, Cochrane Library, Embase via Ovid, CINAHL Plus and Medline via EBSCOhost, ProQuest and PsycINFO from inception to 31 August 2017. Keywords, such as "vitamin K", "refusal", "decline", "hesitancy", and "vaccination" were used to identify potential studies. Analysis of proportions was conducted, while odd ratios and relative risks were estimated using the random effect model.
RESULTS
Of the 2216 studies identified, 8(0.36%) were subjected to qualitative analysis; 4(50%) retrospective cohort studies and 4(50%) cross-sectional studies. Overall, 6(75%) studies were of good quality, while 2(25%) were ranked as of fair quality. Of the 273,714 parents, 3,136(1.14%) refused to opt for the vitamin K prophylaxis. Meta-analysis concluded that refusal to vitamin K prophylaxis was significant among the included studies ((p<0.184).
CONCLUSIONS
The overall risk of refusal to essential vaccination among vitamin K prophylaxis refusal group was 6.45 times compared to the group that accepted vitamin K prophylaxis.
Topics: Infant, Newborn; Humans; Vitamin K; Retrospective Studies; Cross-Sectional Studies; Treatment Refusal; Vaccination Refusal; Parents; Vitamins; Dietary Supplements
PubMed: 37013297
DOI: 10.47391/JPMA.3914 -
Revista Espanola de Cardiologia... Sep 2023Direct oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
Direct oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with bioprosthetic valves are unclear, as this population has been underrepresented in clinical trials. The aim of this study was to assess the safety and efficacy of DOACs in this population based on the existing published literature.
METHODS
A systematic search and review were conducted to identify randomized clinical trials and comparative observational studies published from 2017 to January 2022 that compared DOACs and vitamin K antagonists (VKAs) in AF patients with bioprosthetic valves. Hazard ratios (HR) were collected to compare the 2 treatments in terms of cardiovascular and all-cause mortality, stroke/systemic embolism, and major bleeding. A meta-analysis combining the results was performed.
RESULTS
We included 12 studies (30 283 patients). DOACs and VKAs were compared based on HRs at the 95% confidence interval. DOAC therapy was associated with a significant 9% reduction in all-cause mortality (HR, 0.91; 95%CI, 0.85-0.97; P=.0068; I=8%), with no significant differences in the risk of stroke/systemic embolism (HR, 0.87; 95%CI, 0.67-1.14; P=.29; I=45%) or major bleeding (HR, 0.82; 95%CI, 0.67-1.00; P=.054; I=48.7%).
CONCLUSIONS
DOAC therapy in AF patients with bioprosthetic valves may be associated with a significant reduction in all-cause mortality, with no reduction in the efficacy of stroke/systemic embolism prevention or increase in major bleeding risk.
Topics: Humans; Atrial Fibrillation; Anticoagulants; Hemorrhage; Stroke; Embolism; Administration, Oral; Vitamin K
PubMed: 36804556
DOI: 10.1016/j.rec.2023.02.002 -
Journal of Thrombosis and Thrombolysis Apr 2022The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries. The... (Meta-Analysis)
Meta-Analysis
The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries. The objective of this systematic review and meta-analysis was to summarize the evidence for the efficacy and safety of lower versus higher INR targets in Western and East Asian left-sided mechanical heart valve patients. We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data in addition to grey literature for Randomized Controlled Trials (RCTs) and observational studies. We pooled risk ratios (RRs) using random-effects model. Low and high INR targets were defined by the individual studies. We identified nine RCTs, including six Western (n = 5496) and three East Asian (n = 209) trials, and 17 observational studies, including two Western (n = 3199) and 15 East Asian (n = 5485) studies. In the RCTs, lower compared with higher targets were associated with similar rates of thromboembolism (2.4 vs. 2.3%; RR: 1.14, 95% CI 0.82, 1.60, I = 0%) and lower rates of both total bleeding (21.9 vs. 40.9%, RR: 0.46, 95% CI 0.28, 0.78, I = 88%) and major bleeding. RCT data showed no statistical heterogeneity by region. These effects were consistent in the observational data. We downgraded the quality of evidence due to serious risk of bias and imprecision. In patients with left-sided contemporary mechanical heart valves, low quality evidence suggests lower INR targets are associated with similar rates of thromboembolism and moderate quality evidence suggests lower rates of bleeding.
Topics: Anticoagulants; Fibrinolytic Agents; Heart Valves; Hemorrhage; Humans; Thromboembolism; Vitamin K
PubMed: 34622377
DOI: 10.1007/s11239-021-02568-3 -
Oral Surgery, Oral Medicine, Oral... Mar 2023The recommendations for the management of direct oral anticoagulants (DOACs) in oral surgery are inconsistent. The present review evaluated whether DOACs increase the... (Review)
Review
OBJECTIVE
The recommendations for the management of direct oral anticoagulants (DOACs) in oral surgery are inconsistent. The present review evaluated whether DOACs increase the risk of bleeding during oral surgery and postoperative complications.
STUDY DESIGN
The patients undergoing oral surgery and receiving a DOAC were compared with the patients receiving a DOAC different from the exposure, a vitamin K antagonist (VKA), or no anticoagulant. Three electronic databases were searched for eligible clinical trials and systematic reviews. The risk of bias was assessed, data were extracted, a meta-analysis was done, and the Grading of Recommendations, Assessment, Development and Evaluations certainty-of-evidence ratings were determined.
RESULTS
Three clinical trials comparing patients receiving DOAC medication with patients on a VKA were eligible. A meta-analysis of bleeding 7 days postoperatively detected no significant differences between patients continuing DOAC or VKA medication during and after surgery. All of the point estimates favored uninterrupted DOAC over VKA therapy. Tranexamic acid was topically administered to some patients.
CONCLUSIONS
Based on an interpreted trend among 3 studies with mixed patient populations, the risk of bleeding during the first 7 postoperative days may be lower for patients on uninterrupted DOAC than VKA therapy (⨁⨁⭘⭘), but the effect size of the risk is unclear. 80 of 274 included patients experienced postoperative bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Oral Surgical Procedures; Postoperative Hemorrhage; Tranexamic Acid; Vitamin K
PubMed: 36100547
DOI: 10.1016/j.oooo.2022.07.003 -
Revista Portuguesa de Cardiologia :... Jan 2023Left ventricular thrombus commonly occurs as a complication of acute anterior myocardial infarction and nonischemic cardiomyopathies with severe left ventricular... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Left ventricular thrombus commonly occurs as a complication of acute anterior myocardial infarction and nonischemic cardiomyopathies with severe left ventricular systolic dysfunction. Its frequency is still high despite medical advances. Current guidelines recommend the use of vitamin k antagonists as first-line therapy, however, the off-label use of direct oral anticoagulants is becoming more frequent and attractive, given the better pharmacological and clinical profile, with the improvement of the patient's quality of life.
AIM
To provide an update on the currently existing evidence regarding the outcomes of efficacy and safety of direct oral anticoagulants (DOACs) as first-line therapy in left ventricular thrombus, in comparison to vitamin K antagonists (VKAs).
METHODS
A systematic review and meta-analysis of studies on the effects of direct oral anticoagulants versus vitamin K antagonists on left ventricular thrombi and on the results was performed.
RESULTS
Fourteen studies were included in the meta-analysis, with a total of 2498 patients (n=631 direct oral anticoagulants and n=1867 for VKAs). No significant differences were found in efficacy and safety outcomes (odds ratio (OR) 0.86; 95% confidence interval (CI), 0.55-1.33; p=0.50; I=32%) and (OR 1.0; 95% CI, 0.78-1.30; p=0.93; I=2%) respectively. No difference was noted in all-cause mortality (OR 0.92; 95% CI, 0.58-1.45; p=0.74; I=0%). Thrombus resolution was observed in 288/416 in direct oral anticoagulants vs. 732/1085 patients treated with VKAs (OR 1.14; 95% CI, 0.77-1.66; p=0.50; I=33%).
CONCLUSIONS
The findings of this meta-analysis suggest the potential utility of DOACs as a first-line strategy in patients with left ventricular thrombus.
Topics: Humans; Warfarin; Quality of Life; Anticoagulants; Thrombosis; Fibrinolytic Agents; Administration, Oral; Vitamin K
PubMed: 36370988
DOI: 10.1016/j.repc.2021.11.013 -
Clinical Otolaryngology : Official... Mar 2022Epistaxis is the most common otolaryngological emergency and up to one third of patients in treated on an inpatient basis take oral anticoagulants (OAC). Direct oral... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Epistaxis is the most common otolaryngological emergency and up to one third of patients in treated on an inpatient basis take oral anticoagulants (OAC). Direct oral anticoagulants (DOAC), an OAC subgroup, have been on the market since 2010 and are being increasingly prescribed due to the cardiological and haematological guidelines that favour them over vitamin K antagonists (VKA), the older of the OAC subgroups. The present study aims to investigate which subgroup of epistaxis patients taking OACs has a more favourable outcome.
DESIGN/SETTING
A systematic review and meta-analysis were performed according to the PRISMA 2020 statement using the PubMed and Cochrane Library databases. Continuous data were analysed and standardised mean difference (SMD) was calculated according to Hedges' g. Dichotomous data were analysed, and the Mantel-Haenszel method was applied to establish the odds ratio (OR). Heterogeneity was assessed according to the I statistics.
MAIN OUTCOME/RESULTS
A total of eight reports covering 1390 patients were included in the final synthesis. The pooled analysis demonstrated significantly shorter hospital stays in the DOAC group (SMD = -0.22, 95% CI-0.42 to -0.02, p = .03) and a significantly higher rate of posterior bleeding in the VKA group (OR = .39, 95% CI 0.23 to 0.68, p = .001). No statistically significant differences with regard to recurrence rates, admission rates, the need for transfusion or surgical intervention (p = .57, .12, .57 and .38 respectively) were found.
CONCLUSION
According to this meta-analysis, epistaxis patients taking DOACs have a more favourable outcome than patients taking VKAs.
Topics: Administration, Oral; Anticoagulants; Epistaxis; Hospitalization; Humans; Vitamin K
PubMed: 34812585
DOI: 10.1111/coa.13898 -
Neuroepidemiology 2024Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants versus Warfarin in Patients with Atrial Fibrillation and Previous Stroke: A Systematic Review and Meta-Analysis.
INTRODUCTION
Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke is inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke.
METHODS
We searched studies published up to December 10, 2022, on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischaemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion.
RESULTS
Six randomized controlled trials (RCTs) (including 19,489 patients with previous IS) and fifteen observational studies (including 132,575 patients with previous IS and 13,068 patients with previous ICrH) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.75-0.96), ICrH (OR: 0.57, 95% CI: 0.36-0.90), and all-cause mortality (OR: 0.88, 95% CI: 0.80-0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR: 0.66, 95% CI: 0.46-0.95 vs. OR: 0.80, 95% CI: 0.70-0.93) in the comparison between NOACs and warfarin.
CONCLUSIONS
Observational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS, and further large RCTs focused on patients with previous ICrH are warranted.
Topics: Adult; Humans; Warfarin; Atrial Fibrillation; Vitamin K; Anticoagulants; Stroke; Intracranial Hemorrhages; Thromboembolism; Ischemic Stroke; Treatment Outcome
PubMed: 37848006
DOI: 10.1159/000534596