vitamin-k-semiquinone-radical and Heart-Diseases

Aim    To perform a systematic review and meta-analysis of efficacy and safety of direct oral anticoagulants (DOAC) as compared to vitamin K antagonists (VKA) in the treatment of left ventricular (LV) thrombosis.Material and methods    A search was performed in PubMed and Google Scholar for studies that compared DOAC and VKA in the treatment of LV thrombosis with respect of thromboembolic events, hemorrhagic complications, and thrombus resolution. The effect was evaluated with the odds ratio (OR) that was computed using a fixed effects model.Results    For these systematic review and meta-analysis, 19 studies were selected, including 2 randomized and 17 cohort studies. The articles included into these systematic review and meta-analysis, were published from 2018 through 2021. In total, 2970 patients (mean age, 58.8 лет; 1879 (61.2 %) men) with LV thrombus were included into the meta-analysis. Mean follow-up duration was 17.9 months. The meta-analysis showed no significant difference between DOAC and VKA in the incidence of the study outcomes: thromboembolic events (OR, 0.86; 95 % CI: 0.67-1.10; р=0.22), hemorrhagic complications (OR, 0.77; 95 % CI: 0.55-1.07; р=0.12), thrombus resolution (OR, 0.96; 95 % CI: 0.76-1.22; р=0.77). In a subgroup analysis, rivaroxaban compared to VKA significantly (79%) reduced the risk of thromboembolic complications (OR, 0.21; 95 % CI: 0.05-0.83; р=0.03) with no significant differences in hemorrhagic events (OR, 0.60; 95 % CI: 0.21-1.71; р=0.34) or thrombus resolution (OR, 1.44; 95 % CI: 0.83-1.31; р=0.20). The apixaban treatment group had significantly more (4.88 times) cases of thrombus resolution than the VKA treatment group (OR, 4.88; 95 % CI: 1.37-17.30; р=0.01); for apixaban, data on hemorrhagic and thromboembolic complications were not available.Conclusions    The therapeutic efficacy and side effects of the DOAC treatment for LV thrombosis were similar to those of VKA with respect of thromboembolic events, hemorrhage, and thrombus resolution.

Topics: Anticoagulants; Female; Fibrinolytic Agents; Heart Diseases; Humans; Male; Middle Aged; Thromboembolism; Thrombosis; Vitamin K

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, far ahead of cancer. Epidemiological data emphasize the participation of many risk factors that increase the incidence of CVDs, including genetic factors, age, and sex, but also lifestyle, mainly nutritional irregularities and, connected with them, overweight and obesity, as well as metabolic diseases. Despite the importance of cardiovascular problems in the whole society, the principles of prevention of CVDs are not widely disseminated, especially among the youngest. As a result, nutritional neglect, growing from childhood and adolescence, translates into the occurrence of numerous disease entities, including CVDs, in adult life. This review aimed to draw attention to the role of selected minerals and vitamins in health and the development and progression of CVDs in adults and children. Particular attention was paid to the effects of deficiency and toxicity of the analyzed compounds in the context of the cardiovascular system and to the role of intestinal microorganisms, which by interacting with nutrients, may contribute to the development of cardiovascular disorders. We hope this article will draw the attention of society and the medical community to emphasize promoting healthy eating and proper eating habits in children and adults, translating into increased awareness and a reduced risk of CVD.

Topics: Adolescent; Adult; Cardiovascular Diseases; Child; Gastrointestinal Microbiome; Heart Diseases; Humans; Minerals; Vitamin A; Vitamin K; Vitamins

One of the most catastrophic complications of Atrial fibrillation (AF) is thromboembolic stroke. Current guidelines recommend that 3 weeks of anticoagulation is adequate prior to direct current cardioversion (DCCV) to prevent thromboembolism. Here we present data regarding, which anticoagulant is most likely to show a presence of an Left atrial appendage thrombus (LAAT) on trans esophageal echocardiogram (TEE) for DCCV despite 3 weeks of anticoagulation.. To investigate the effectiveness of both vitamin k antagonist (VKA) and direct oral anticoagulants (DOAC) in patients with AF as an anticoagulant for LAAT after 3 weeks of medication.. This is a single-high volume tertiary center, where TEE precardioversion is the standard practice. We reviewed data over 10 months where DCCV was intended on individuals with AF who were fully anticoagulated for at least 3 weeks with either a VKA or taking a DOAC.. The data showed a statistical difference between patients who were fully anticoagulated for at least 3 weeks with VKA in comparison to DOACs. Patients on DOACs are significantly less likely to have an LAAT after at least 3 weeks of anticoagulation. OR = 0.04 (CI 95% 0.005-0.42; p-value < .05). Despite anticoagulation for at least 3 weeks, 40% of our patients still had a LAAT.. Our data indicates that all patients should be required to undergo a TEE prior to DCCV. This data also adds to the current evidence and supports the use of DOAC in AF to prevent LAAT.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Electrocardiography; Fibrinolytic Agents; Heart Diseases; Humans; Incidence; Thrombosis; Vitamin K

To compare the safety and efficacy of direct oral anticoagulants (DOAC) relative to vitamin K antagonists (VKA) for the treatment of left ventricular thrombus (LVT).. This retrospective study enrolled patients diagnosed with LVT from 2014-2017. Patient characteristics and outcomes within 12 months of LVT diagnosis were recorded and analyzed. A meta-analysis was also performed by pooling our results with existing data in literature.. 14 DOAC and 59 VKA patients were included. Baseline demographic and clinical characteristics were similar except for age. Although more strokes within 12 months occurred in VKA (15%) than in DOAC (0%) patients, this was not statistically significant (. Our study and meta-analysis suggest similar efficacy and safety of DOACs in the treatment of LVT compared to VKA. These findings underscore the need for a randomized controlled trial.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Coronary Thrombosis; Female; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

There is still a paucity of data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) in the prevention of left atrial thrombus (LAT) formation before cardioversion or catheter ablation. To assess the efficacy of NOACs in the prevention of LAT in patients with non-valvular atrial fibrillation (NVAF) compared with vitamin K antagonists (VKAs), we conducted a meta-analysis.. We searched PubMed, Embase, and the Cochrane Library databases. For meta-analysis, dichotomous variables were analyzed by using the odds ratios (OR) computed using the Mantel Haenszel method (random models). All results were reported with 95% confidence intervals (CI).. A total of 13 studies (one randomized controlled investigation and 12 observational studies) were included in the meta-analysis. There was no statistically significant difference between the NOACs and VKAs groups with respect to the odds of LAT/LAAT formations (OR 0.79; 95% CI: 0.52-1.21; P = .29; (I2 = 14%).. NOACs were as effective as VKAs in the prevention of LAT/LAAT formation in patients with NVAF. Though patients on NOACs therapy showed a lower incidence of LAT/LAAT formation compared with VKAs, it was not significant (P = .29).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Heart Atria; Heart Diseases; Humans; Thrombosis; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Atrial Fibrillation; Benzamides; Biomarkers; Blood Coagulation; Clinical Trials as Topic; Dabigatran; Drug Administration Schedule; Factor Xa; Heart Diseases; Humans; Piperazines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Risk; Rivaroxaban; Stroke; Thiazoles; Thrombin; Venous Thromboembolism; Vitamin K; Warfarin

Intracardiac thrombus most commonly develops in the left atrial appendage (LAA) and left ventricle (LV) in the setting of atrial fibrillation (AF) and post-myocardial fibrillation (MI), respectively. Current guidelines recommend that patients with post-MI LV or LAA thrombus should be treated with vitamin K antagonist (VKA). However, the use of VKA may be limited by bleeding complications, interactions with various food and drugs, and a narrow therapeutic window requiring frequent monitoring. Thus, non-VKA oral anticoagulants (NOACs) have been attempted as an off-label use for the treatment of intracardiac thrombosis in light of their favorable pharmacologic profile. Until now, therapeutic effect of NOACs on intracardiac thrombosis has not been formally studied in large randomized controlled trials. This article aims to systematically review the literature regarding efficacy and safety outcome of NOACs in the management of intracardiac thrombus. Considering the high rate of complete thrombus resolution and low rate of thromboembolic or hemorrhagic complications, preliminary evidence from case series and reports indicate that NOACs (including factor Xa inhibitors and direct thrombin inhibitors) may be a safe and effective therapeutic option for intracardiac thrombosis, particularly in cases resistant to VKA therapy.

Topics: Anticoagulants; Antithrombins; Coronary Thrombosis; Factor Xa Inhibitors; Heart Diseases; Humans; Vitamin K

Oral anticoagulation and antiplatelet therapy are risk factors for gastrointestinal (GI) bleeding. GI bleeding-especially lower GI bleeding-seems to be associated with a poorer outcome. With the introduction of dabigatrane and rivaroxaban, difficulties in the management of bleeding complications arose. Thus, the goal of the authors was to establish a standard operating procedure (SOP) for the treatment of severe GI bleeding associated with rivaroxaban, dabigatrane, and antiplatelet therapy. Bleeding complications during phenprocoumon treatment should be treated with prothrombin complex concentrates and vitamin K1. Dabigatrane elimination is highly dependent to the renal function. The measurement of drug concentrations of dabigatrane and rivaroxaban is useful to indicate an increased risk of bleeding complications. Severe bleeding associated with dabigatrane or rivaroxaban therapy should trigger prothrombin complex therapy, whereby in cases with severe bleeding associated with antiplatelet therapy platelet transfusion should be initiated. Low-dose aspirin should be continued after 24 h.

Topics: Algorithms; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Dabigatran; Drug Monitoring; Gastrointestinal Hemorrhage; Heart Diseases; Humans; Metabolic Clearance Rate; Morpholines; Phenprocoumon; Platelet Aggregation Inhibitors; Platelet Transfusion; Rivaroxaban; Thiophenes; Vitamin K

Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting γ-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.

Topics: Advisory Committees; Anticoagulants; Blood Coagulation; Cardiology; Europe; Heart Diseases; Humans; Societies, Medical; Thrombosis; Vitamin K

Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Drug Monitoring; Fibrinolytic Agents; Heart Diseases; Humans; International Normalized Ratio; Intracranial Embolism; Primary Prevention; Risk; Secondary Prevention; Stroke; Thrombophilia; Vitamin K

Stroke and atrial fibrillation (AF) constitute a true vascular epidemic with catastrophic consequences. The most common and devastating complication of AF is cardioembolic stroke but this catastrophic event can be predicted and prevented. Accurate etiologic diagnosis of stroke is essential for effective prevention. The percentage of cryptogenic ischemic strokes is too high and detection of AF and other causes of cardioembolic events should be improved. Cardioembolic cerebral ischemia can be prevented. However, because of physician inertia, lack of patient adherence and the problems of vitamin K antagonists, many patients are at risk of cerebral ischemia. Recently, major advances with drugs such as dronedarone, dabigatran and FXa inhibitors have opened the way to improving stroke prevention, as reflected in therapeutic guidelines, and neurologists should be familiar with these drugs. There is reason to hope that much suffering can be avoided.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Ischemia; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Intracranial Embolism; Multicenter Studies as Topic; Prevalence; Randomized Controlled Trials as Topic; Risk Factors; Single-Blind Method; Thrombophilia; Vitamin K

On of the most common, and serious, complications in cardiac surgery is postoperative bleeding. According to the majority of studies, between 10% and 92% of patients subjected to elective surgery require transfusions of blood products and blood derivatives. Transfusions and reinterventions are associated with longer stays in critical care units and a decrease in survival rates. There have been some important changes in the treatment of changes in haemostasis and post-surgical bleeding in the last few years, particularly with the introduction into clinical practice of working procedures backed up by clinical guidelines, as well as the appearance of new drugs. The aim of this work is to describe the main characteristics and update the use of prothrombin complexes that are currently available in Spain, with special emphasis on their use in cardiac surgery.

Topics: Anticoagulants; Blood Coagulation Factors; Blood Loss, Surgical; Blood-Borne Pathogens; Cardiac Surgical Procedures; Contraindications; Disease Transmission, Infectious; Drug Contamination; Drug Costs; Heart Diseases; Hemorrhagic Disorders; Hemostatics; Humans; Postoperative Hemorrhage; Preanesthetic Medication; Thrombophilia; Thrombosis; Vitamin K

Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 2 Receptor Blockers; Anticoagulants; Atrial Fibrillation; Cardiology; Coronary Disease; Drug-Eluting Stents; Heart Diseases; Humans; Morpholines; Myocardial Infarction; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Cardioembolism accounts for approximately 20% of ischaemic strokes, and is associated with high mortality and propensity to recurrences. Approximately, 30% of ischaemic strokes remain cryptogenic despite improved imaging modalities and technological improvements to identify their cause. Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause. Unsurprisingly, the stroke risk associated with these conditions is highly variable and non-homogenous, with many risk factors additive to the overall risk profile. Treatment with vitamin K-antagonists substantially reduces the long-term complications associated with cardioembolism in some high-risk patients, for example, in atrial fibrillation. Careful selection of antithrombotic drug regime needs to be carried out in patients individually to minimise the risk of bleeding encountered with such therapy. Apart from atrial fibrillation, there is relatively limited evidence for the role of antithrombotic therapy for other cardiac conditions associated with cardioembolism and how long one should treat.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Heart Diseases; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Myocardial Infarction; Stroke; Thrombosis; Vitamin K

Provided that account is taken of the criteria discussed in the present article, there is no doubt about the therapeutic benefits of effective anticoagulation in patients with chronic atrial fibrillation. Indeed, it is to be expected that the previously valid therapeutic guidelines are more likely to be expanded to reduce feared thromboembolic complications to a minimum, as is exemplified by the recommendation that the application of anticoagulation treatment with vitamin K antagonists should be continued over the longer term, that is, after the restoration of sinus rhythm. Furthermore, there is hope that effective drugs with a calculable (level of) safety and simplicity of administration may soon become available.

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Echocardiography; Electric Countershock; Fibrinolytic Agents; Heart Diseases; Humans; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Stroke; Thromboembolism; Thrombosis; Time Factors; Vitamin K

The purpose of this study was to compare two different intensities of vitamin K antagonists (VKA) among patients with mechanical heart valves using meta-analytic techniques.. Patients with mechanical heart valves are at increased risk for valve thrombosis and systemic embolism, which can be reduced by VKA. The range of optimal intensity of VKA is still a matter of debate.. A computerized search in the PubMed database was made for relevant articles. A meta-analysis was performed of all eligible studies with data on the incidences of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses during different intensities of VKA therapy. The studies were classified into low-intensity VKA therapy (mean target international normalized ratio [INR] of 3.0 or lower) or high-intensity VKA therapy (mean target INR above 3.0).. Thirty-five eligible studies were identified, including in total 23,145 patients, who were studied for 108,792 patient-years. For patients with an aortic valve, high intensity resulted in a lower incidence of thromboembolic events (risk ratio [RR] = 0.73, p < 0.0001); however, the incidence of bleeding was increased (RR = 1.23, p < 0.0001). In the mitral valve group, the incidence rate for thromboembolism was lower in the high-intensity group (RR = 0.74, p < 0.0001), without a significantly increased bleeding incidence (RR = 1.08, p = 0.0524). The total number of thromboembolic and bleeding events was decreased in the high-intensity group compared with low-intensity VKA therapy for both aortic and mitral valve prostheses (RR = 0.94 [p = 0.0067] and 0.84 [p < 0.0001]), respectively.. This meta-analysis shows that both aortic and mitral valves will benefit from a treatment strategy with a target INR higher than 3.0.

Topics: Aortic Valve; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Thromboembolism; Vitamin K

To evaluate the therapeutic impact of an education program on patients undergoing oral anticoagulation treatment, within the hospital of Annecy (France).. Groups of 10 patients were invited to participate to two meetings. The education was carried out by two nurses. Thanks to this prospective study, we compare the population before and after education in terms of treatment knowledge and stability.. Within 9 months 88 patients have been included, amongst which 55 have attended the two meetings. The average of correct answers to the knowledge evaluation questionnaire distributed before and after 6 months of education were, respectively, 6.63/12, 10.09/12 (P < 0.0001). Through INR controls within the 6 months preceding (424 controls) and the 6 months following the education (619 controls), we observe: an increase of the total INR average in therapeutic zone, from 45% to 61% (P < 0.0001); a decrease of the difference average per patient between the INR value observed and the one targeted: 0.54 before education, 0.40 after education (P = 0.0016); at last, the average phasing per patient under the therapeutic zone increases after education, from 49% to 65% (P < 0.001).. The education improves objectively the knowledge of patient undergoing AVK. If the size of patient sample is not large enough to prove any consequence on hemorrhagic or thrombotic complications, the education program still improves significantly the treatment stability.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Chi-Square Distribution; Data Interpretation, Statistical; Female; Heart Diseases; Humans; Male; Middle Aged; Patient Education as Topic; Patient Satisfaction; Phenindione; Surveys and Questionnaires; Thromboembolism; Time Factors; Vitamin K

Topics: Antidepressive Agents; Antihypertensive Agents; Appetite Depressants; Blood Coagulation Disorders; Cardiovascular Diseases; Contraceptives, Oral; Coronary Disease; Daunorubicin; Dihydroxyphenylalanine; Heart Diseases; Humans; Iatrogenic Disease; Imipramine; Monoamine Oxidase Inhibitors; Phenothiazines; Shock, Cardiogenic; Transfusion Reaction; Vitamin K

Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.. The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.. Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis.. a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy.. From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels.. In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).

Topics: Adult; Anticoagulants; Child; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Pyridones; Quality of Life; Venous Thromboembolism; Vitamin K

Anticoagulation in children is problematic for multiple reasons. Currently used anticoagulants have significant disadvantages and may negatively affect quality of life (QOL). This manuscript describes the design, rationale, and methods of a prospective, randomized, open label phase II multi-national clinical trial of a direct oral anticoagulant (DOAC), apixaban, in children and infants with congenital and acquired heart disease. This trial is designed to gather preliminary safety and pharmacokinetics (PK) data, as well as generate data on QOL of individuals taking apixaban compared to the standard of care (SOC) anticoagulants vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). A key issue this trial seeks to address is the practice of using therapeutics tested in adult trials in the pediatric population without robust pediatric safety or efficacy data. Pediatric heart diseases are not common, and specific diagnoses often meet the criteria of a rare disease; thus, statistical efficacy may be difficult to achieve. This trial will provide valuable PK and safety data intended to inform clinical practice for anticoagulation in pediatric heart diseases, a setting in which a fully powered phase III clinical trial is not feasible. A second consideration this trial addresses is that metrics besides efficacy, such as QOL, have not been traditionally used as endpoints in regulated anticoagulation studies yet may add substantial weight to the clinical decision for use of a DOAC in place of VKA or LMWH. This study examines QOL related to both heart disease and anticoagulation among children randomized to either SOC or apixaban. There are considerable strengths and benefits to conducting a clinical trial in pediatric rare disease populations via an industry-academic collaboration. The SAXOPHONE study represents a collaboration between Bristol-Myers Squibb (BMS)/Pfizer Alliance, and the National Heart, Lung, and Blood Institute's (NHLBI) Pediatric Heart Network (PHN) and may be an attractive model for future pediatric drug trials.

Topics: Adolescent; Anticoagulants; Child; Child, Preschool; Clinical Trials, Phase I as Topic; Factor Xa Inhibitors; Female; Heart Defects, Congenital; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Multicenter Studies as Topic; Prospective Studies; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Sample Size; Vitamin K

To assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE).. All children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models.. We included 405 patients. Median follow-up was 18.7 (9.3-49.4) months. The median TTR was 83.1 % (74.4 %-95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1-1.8]) and 2.3 % (CI95 % [0.9-3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %-99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2-8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6-11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5-15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9-32.0], p = 0.005) was the only risk factor for thrombotic events.. Overall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Topics: Anticoagulants; Atrial Fibrillation; Child; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; Prospective Studies; Risk Factors; Thrombosis; Vitamin K

Topics: Anticoagulants; Heart Diseases; Humans; Off-Label Use; Thrombosis; Vitamin K

It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis.. A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis.. 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029).. In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; COVID-19; COVID-19 Drug Treatment; Factor Xa Inhibitors; Female; Follow-Up Studies; Heart Diseases; Hemorrhage; Humans; Intensive Care Units; Male; Metabolic Diseases; Middle Aged; Mortality; Treatment Outcome; Vitamin K

Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death.. We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported.. The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

Topics: Adult; Aged; Anticoagulants; Catheterization, Central Venous; Conservative Treatment; Female; Fibrinolytic Agents; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Renal Dialysis; Thrombosis; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vitamin K

Topics: Aged, 80 and over; Anesthesia, Epidural; Anticoagulants; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Emergency Medical Services; Female; Heart Diseases; Humans; Nerve Block; Risk Assessment; Treatment Outcome; Vitamin K

Intracardiac thrombosis is a rare complication of Behçet's disease (BD), which may manifest as intracardiac tumor. In half of cases, its detection precedes the diagnosis of MB. High mortality rates may be related to post-surgical complications and/or pulmonary arteries involvement. We report the case of a 29-year old young patient, with a previous history of bipolar aphthosis, who underwent surgery after the detection of right atrium and ventricle tumor. Anatomo-pathological examination showed thrombus and MB was diagnosed in the postoperative period. Patient's evolution was favorable under medical treatment based on corticosteroids, colchicine and vitamin K antagonists (AVK). The detection of intracardiac mass in a young subject should suggest the diagnosis of cardiac thrombus and Behçet's disease, even in the absence of ethnic or geographical risk factors.

Topics: Adrenal Cortex Hormones; Adult; Behcet Syndrome; Colchicine; Heart Diseases; Heart Neoplasms; Humans; Male; Thrombosis; Vitamin K

Patients undergoing elective electrical cardioversion (ECV) for atrial fibrillation have a temporarily increased risk of thromboembolism. Current guidelines recommend adequate anticoagulation for ≥3 consecutive weeks precardioversion, i.e. consecutive INR values 2.0-3.0 in patients with vitamin K antagonists (VKA). We aimed to evaluate the occurrence and impact of subtherapeutic INRs precardioversion and to study factors associated with these unwanted fluctuations.. We recruited 346 consecutive patients undergoing elective ECV in the Maastricht University Medical Centre between 2008 and 2013. Predictors of subtherapeutic INR values were identified and incorporated into a logistic regression model.. A subtherapeutic INR precardioversion occurred in 55.2% of patients. The only statistically significant predictor was VKA-naivety (Odds Ratio (OR) 4.78, 95% Confidence Interval (CI) 2.67-8.58, p<0.001). In patients with ≥1 subtherapeutic INR precardioversion, time from referral until cardioversion was 91.1±42.8days, compared to 41.7±26.6days (p<0.001) in patients without subtherapeutic INRs. No thromboembolic events occurred <30days after the ECV. Independent predictors for the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion (n=30, median follow-up of 374days) were coronary artery disease in the history (OR 3.35, 95%CI 1.54-7.25, p=0.002) and subtherapeutic INR precardioversion (OR 3.64, 95%CI 1.43-9.24, p=0.007).. The use of VKA often results in subtherapeutic INRs precardioversion and is associated with a significant delay until cardioversion, especially in patients with recent initiation of VKA therapy. Furthermore, subtherapeutic INR levels prior to ECV are associated with the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion.

Topics: Aged; Anticoagulants; Cerebrovascular Disorders; Cohort Studies; Electric Countershock; Female; Follow-Up Studies; Heart Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Prospective Studies; Registries; Time Factors; Vitamin K

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Embolism; Factor Xa Inhibitors; Heart Diseases; Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Morpholines; Multicenter Studies as Topic; Myocardial Infarction; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Risk; Rivaroxaban; Stroke; Thiophenes; Thrombophilia; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists (VKA), the most widely prescribed oral anticoagulant therapy, represent a major public health problem by the adverse events related to their use. The aim of this study was to clarify the level of knowledge that patients have about the management of their oral anticoagulant treatment.. This was a descriptive cross-sectional study performed at Yalgado Ouedraogo university Hospital, over a period of three months starting from March 1st to May 31st 2012. A questionnaire was given to patients receiving VKA treatment for at least a month.. Seventy patients were enrolled in the study of which 30 men. The median age was 49±16 years. Heart disease and venous thromboembolic disease justifying the introduction of VKA treatment were found respectively in 58.6 and 41.4% of the cases. The name of the VKA and the exact reason for the treatment were known respectively in 91.4 and 61.7% of the case. More than half of patients (68.6%) knew that the VKA makes blood more fluid. Forty-six patients (65.7%) cited INR as biological monitoring of treatment but only 28 patients (40%) were aware of INR target values. The majority of patients did not know the risks in case of overdose (72.8%) and underdosing (71.4%). Self-medication by non-steroidal anti-inflammatory drugs was reported by 18 patients (25.7%). Cabbage (74.3%) and lettuce (62.9%) were the main foods reported to be consumed moderately.. The knowledge of patients on the management of VKA is fragmentary and remains insufficient to ensure the effectiveness of the treatment. The creation of a therapeutic education program is then necessary.

Topics: Adult; Aged; Anticoagulants; Burkina Faso; Health Literacy; Heart Diseases; Humans; International Normalized Ratio; Male; Middle Aged; Patient Education as Topic; Patient Medication Knowledge; Surveys and Questionnaires; Vitamin K

Topics: Aged; Anticoagulants; Atrial Appendage; Factor Xa Inhibitors; Female; Heart Diseases; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Tomography, X-Ray Computed; Vitamin K

Managing vitamin K antagonist (VKA) therapy is challenging in children because of a narrow therapeutic range and wide inter- and intra-individual variability in dose response. Only a few small studies have investigated the effect of nongenetic and genetic factors on the dose response to VKAs in children. In a cohort study including 118 children (median age 9 years; range, 3 months-18 years) mostly with cardiac disease, we evaluated by multivariate analysis the relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of these factors on the time spent within/above/below the range. The results showed that height, target international normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin dose requirement, accounting for 48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7% of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7% of patients. None of the covariates was associated with the time spent above or below the international normalized ratio range. Whether this model predicts accurately the effective maintenance dose is currently being investigated.

Topics: Adolescent; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Body Height; Child; Child, Preschool; Cohort Studies; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; DNA; Dose-Response Relationship, Drug; Female; Genotype; Heart Diseases; Humans; Infant; International Normalized Ratio; Male; Mixed Function Oxygenases; Models, Statistical; Polymerase Chain Reaction; Polymorphism, Genetic; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Topics: Anticoagulants; Heart Diseases; Humans; International Normalized Ratio; Nutritional Requirements; Pulmonary Embolism; Thrombophlebitis; Vitamin K; Vitamin K Deficiency

Topics: 4-Hydroxycoumarins; Anticoagulants; Drug Overdose; Factor IX; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Indenes; Male; Middle Aged; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Contraindications; Drug Combinations; Factor Xa Inhibitors; Forecasting; Heart Diseases; Hemorrhage; Hemostasis; Humans; Infusions, Parenteral; Point-of-Care Systems; Risk Factors; Thrombin; Vitamin K

Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with increasing age and the most important complication of the disease is thromboembolic events that may be prevented by antivitamin K. They are the most efficient therapeutic class for the prevention of these events but they are associated with an increased haemorrhagic risk leading to a reduced prescription in general practice. Optimisation of the management should be based on an individual evaluation of the thromboembolic and haemorrhagic risks, taking into account age, the presence of an associated heart disease, hypertension, diabetes, history of cerebrovascular event, history of previous haemorrhagic event and the ability to achieve a stable target INR. The challenge in ventricular arrhythmias lies in identifying a high risk of sudden death, mainly related to ventricular fibrillation. In patients with structural heart disease, left ventricular dysfunction is the strongest predictor of sudden death. Non invasive markers such as non sustained ventricular tachycardia, late ventricular potentials, decreased heart rate variability and baroreflex sensitivity, and repolarization altemans are further elements to assess risk. However, most of these markers have a poor positive predictive value and a low specificity. In patients with normal hearts, genetic predisposition may in the future identify high risk patients. The electrophysiologic study with programmed ventricular stimulation remains a costly and invasive method and only has a strong positive predictive value in ischemic cardiomyopathy. More precise algorithms for risk stratification are thus needed that may help the strategy of therapy with prophylactic implantable cardioverter defibrillator in the future.

Topics: 4-Hydroxycoumarins; Age Factors; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Baroreflex; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Diabetes Complications; Electrocardiography; Heart Diseases; Heart Rate; Hemorrhage; Humans; Hypertension; Indenes; International Normalized Ratio; Myocardial Ischemia; Risk Assessment; Risk Factors; Stroke; Tachycardia, Ventricular; Thromboembolism; Ventricular Dysfunction, Left; Ventricular Fibrillation; Vitamin K

Topics: Aged; Anticoagulants; Drug Monitoring; Female; Follow-Up Studies; Heart Diseases; Humans; International Normalized Ratio; Male; Pharmacokinetics; Treatment Outcome; Vitamin K

Topics: Aortic Valve; Heart Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Mitral Valve; Thromboembolism; Vitamin K

Topics: Aortic Valve; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Mitral Valve; Thromboembolism; Vitamin K

Topics: Heart Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Meta-Analysis as Topic; Mitral Valve; Randomized Controlled Trials as Topic; Thromboembolism; Vitamin K

Oral anticoagulant therapy, which is used for prophylaxis and management of thrombotic disorders, causes similar reductions in plasma levels of vitamin K-dependent procoagulant and anticoagulant clotting factor zymogens. When we measured levels of circulating activated protein C, a physiologically important anticoagulant and anti-inflammatory agent, in patients on oral anticoagulant therapy, the results unexpectedly showed that such therapy decreases levels of activated protein C substantially less than levels of protein C, prothrombin, and factor X, especially at lower levels of prothrombin and factor X. Thus, we suggest that oral anticoagulant therapy results in a relatively increased expression of the protein C pathway compared with procoagulant pathways not only because there is less prothrombin to inhibit activated protein C anticoagulant activity, but also because there is a disproportionately higher level of circulating activated protein C.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Factor X; Heart Diseases; Humans; Lupus Erythematosus, Systemic; Protein C; Prothrombin; Vitamin K

Anticoagulants, including heparins and antivitamins K are medicines which are largely prescribed in cardiology. Even though the outlines of the treatment have been clearly established for a few decades, new cardiological indications have recently appeared. The long-term treatment of cardiac valvular prosthesis by oral anticoagulants significantly reduces the risk of thrombo-embolic incident among people carrying a cardiac valvular prosthesis. In case of non-operated valvulopathy, treatment indication must be evaluated for each patient; in so doing, the connection benefit/risk must always be taken into account. In case of dilated cardiomyopathy, the treatment prescription must be limited to the patients with a high embolic risk. Other cardiological indications (apart from atrial fibrillation) must be carefully weighed up.

Topics: Anticoagulants; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Heart Diseases; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Risk Assessment; Risk Factors; Thromboembolism; Vitamin K

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Blood Coagulation Tests; Heart Diseases; Humans; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Tests; Electronarcosis; Heart Diseases; Humans; Male; Mental Disorders; Middle Aged; Prothrombin; Vitamin K

The hepatic synthesis of vitamin K dependent coagulation factors is modified by oral anticoagulant drugs, resulting in the release of functionally deficient coagulation factors into the circulation and consequently anticoagulation. Since their introduction into clinical medicine over 30 years ago, both clinical and scientific evidence has demonstrated the value of oral anticoagulants in the treatment and prophylaxis of venous thrombosis. In the treatment of arterial disease, however, both the indications for and usefulness of oral anticoagulants remain very much in doubt despite their widespread use in the 1950s and 1960s and in numerous clinical trials. The initiation and continuation of oral anticoagulant therapy is a co-operative venture involving the patient, the clinician and the laboratory. The clinician must have a thorough knowledge of the indications for and contraindications to the use of these drugs, and regular, accurate laboratory control is essential if haemorrhage, the major side effect, is to be avoided or reduced to a minimum. The patient must bear the responsibility for regular clinic attendance, abstinence from proprietary medications, and must immediately seek medical advice if any sign of haemorrhage occurs.

Topics: Age Factors; Aged; Anticoagulants; Drug Interactions; Female; Heart Diseases; Hemorrhage; Humans; Myocardial Infarction; Pregnancy; Sex Factors; Thrombophlebitis; Vitamin K

Topics: Acute Disease; Aged; Anticoagulants; Blood Cell Count; Blood Glucose; Embolism; Heart Diseases; Hemorrhage; Heparin; Humans; Male; Myocardial Infarction; Nitrogen; Rupture, Spontaneous; Thrombosis; Vitamin K

Topics: Animals; Chlortetracycline; Dietary Carbohydrates; Female; Glucose; Heart Diseases; Hemorrhage; Male; Prothrombin Time; Rats; Salicylates; Sucrose; Swine; Swine Diseases; Syndrome; Vitamin K

Topics: Adolescent; Adult; Aged; Anticoagulants; Blood Pressure; Blood Transfusion; Coumarins; Female; Follow-Up Studies; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Heart Diseases; Heparin; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Prothrombin; Thromboembolism; Vitamin K

Topics: Cytochromes; Female; Heart Diseases; Humans; Inositol; Pregnancy; Vitamin A; Vitamin K; Vitamins