vitamin-k-semiquinone-radical and Heart-Valve-Diseases

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have several advantages over VKAs that render them an attractive option for adults with congenital heart disease (CHD). Efficacy and safety data specific to the adult CHD population are emerging. Herein, we synthesize the growing literature regarding NOACs in adults with CHD and attempt to identify subgroups for which it appears reasonable to extrapolate data from populations without CHD. Small observational studies suggest that NOACs are safe and effective in selected adults with CHD. NOACs are contraindicated in patients with a mechanical valve, in those with mitral or tricuspid valve stenosis with enlarged and diseased atria, with or without a mitral or tricuspid bioprosthesis, and after recent cardiac surgery (< 3 months). There is currently insufficient evidence to recommend NOACs in patients with a Fontan circulation or cyanotic CHD. Growing literature supports the use of NOACs in patients without CHD who have various forms of valvular heart disease. Therefore, when an indication for oral anticoagulation is established, it appears reasonable to consider a NOAC instead of a VKA in adults with CHD lesions analogous to isolated mitral regurgitation, tricuspid regurgitation, or aortic regurgitation or stenosis. The NOAC agent selected and the prescribed dose should be tailored according to bleeding risk, body weight, renal function, and comedications, especially antiepileptic drugs. The decision to initiate a NOAC should be shared between the patient and care provider. Large-scale research studies are required to further assess safety and efficacy in selected patient subgroups.

Topics: Administration, Oral; Adult; Age Factors; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Dabigatran; Female; Heart Defects, Congenital; Heart Valve Diseases; Humans; Male; Prognosis; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Severity of Illness Index; Sex Factors; Stroke; Survival Analysis; Thiazoles; Vitamin K

The non-vitamin K antagonist oral anticoagulants (NOACs) were approved for non-valvular atrial fibrillation (AF) but this term may be misnomer. Thus, the term non-mechanical and rheumatic mitral valvular (non-MARM) AF was proposed to exclude patients with valvular heart disease (VHD) without contraindications for NOACs. We aimed to review the efficacy and safety of NOACs in patients with AF and VHD compared to Vitamin K Antagonists (VKA). We performed a systematic review with meta-analysis (PROSPERO CRD42015024837) including data from randomized controlled trials (RCTs) retrieved in November 2016. The efficacy and safety data were pooled using random-effects meta-analyses using the hazard ratio (HR) with the 95% confidence interval (95%CI). Trial sequential analysis (TSA) was performed in statistical significant results to evaluate whether cumulative sample size was powered for the obtained effect. In 5 RCTs (with 12 653 VHD AF patients), NOACs significantly reduced the risk of stroke and systemic embolism (HR 0.73, 95%CI:0.60-0.90; TSA showed estimate was robust - O'Brien-Fleming α-spending boundary crossed before reaching the estimated information size) and intracranial hemorrhage (HR 0.45, 95%CI:0.24-0.87) compared with VKA. Major bleeding risk was not significantly different. In patients with bioprosthesis (3 trials-280 patients) the risks of thromboembolism (HR 0.65, 95%CI:0.20-2.08) and major bleeding (HR 0.94, 95%CI:0.28-3.18) with NOACs were similar to VKA. NOACs are efficacious and safe in patients with non-MARM VHD AF, showing significant reduction in the risk of stroke and systemic embolism and intracranial hemorrage compared with VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Humans; Risk Factors; Thromboembolism; Vitamin K

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Blood Coagulation; Cardiac Surgical Procedures; Cardiology; Child; Coronary Artery Bypass; Drug Administration Schedule; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Diseases; Heart-Assist Devices; Hemorrhage; Hemostasis; Heparin; Humans; Inflammation; Intraoperative Period; Perioperative Period; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Protamines; Risk; Thrombolytic Therapy; Thrombosis; Vitamin K

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with "non-valvular AF", and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease.

Topics: Administration, Oral; Aging; Anticoagulants; Antithrombins; Atrial Fibrillation; Body Weight; Diabetes Mellitus; Factor Xa Inhibitors; Heart Valve Diseases; Hemorrhage; Humans; Kidney Diseases; Risk Factors; Stroke; Vitamin K

The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).. Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).. Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Atrial fibrillation (AF) is associated with a markedly increased risk of thromboembolic events, particularly in patients with valvular AF. Recent trials comparing vitamin K antagonists with non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in AF excluded most patients with valvular AF. Although the definition of valvular AF is disputed, the lack of evidence regarding the use of NOACs for these patients is not. We discuss the definition of valvular AF, the risk of thromboembolism, and the antithrombotic treatment for stroke prevention in these patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Stroke; Thromboembolism; Vitamin K

Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.. This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.. We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.. Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).. High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.

Topics: Anticoagulants; Atrial Fibrillation; Heart Valve Diseases; Hemorrhage; Humans; Stroke; Vitamin K

Long-term anticoagulation is required in all patients with mechanical prosthetic heart valves to prevent complications with valve thrombosis and valve failure or systemic thromboembolism. The prothrombotic environment of pregnancy further increases the risks of these complications. Anticoagulant choices for pregnant women include oral vitamin K antagonists such as warfarin, or heparin - either unfractionated heparin (UFH) or low molecular weight heparin (LMWH). None of the options is without risk for the mother or her baby. Warfarin crosses the placenta and is associated with warfarin embryopathy and fetopathy but is very effective at preventing thromboembolic complications. The dose of warfarin may play a role in the risk of some, but not all fetal complications. Heparin does not cross the placenta but is less effective at preventing thrombosis and LMWH may be more effective than UFH. The optimal dose and target anti-Xa levels for LMWH have not been established. Measurement of trough anti-Xa levels in addition to peak anti-Xa levels may be important.

Topics: Anticoagulants; Cohort Studies; Factor Xa; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Maternal Exposure; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Risk; Thromboembolism; Thrombosis; Vitamin K; Warfarin

New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.

Topics: Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Embolism; Factor Xa Inhibitors; Female; Heart Valve Diseases; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Morpholines; Multicenter Studies as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Vitamin K; Warfarin

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Anticoagulants; Calcinosis; Diphosphonates; Heart Valve Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperbaric Oxygenation; Muscle, Smooth, Vascular; Osteoprotegerin; Vitamin K; Warfarin

Surgical replacement of a native valve with a biological or mechanical prosthesis is the definitive treatment for many forms of advanced valvular heart disease. Mechanical heart valves are less prone to structural deterioration compared with bioprostheses, but require chronic oral anticoagulation to prevent thromboembolic events. Thromboembolic risk varies based on patient-related risk factors, including atrial fibrillation, advanced age, low ejection fraction, and hypercoagulability. Other important correlates of high thromboembolic risk include valve design, valve position, anticoagulation variability, and time from surgery. Clinical management is further complicated when antithrombotics may need to be interrupted or altered during surgery or pregnancy. At present, vitamin K antagonists are the only approved agents for thromboprophylaxis but are limited because of a narrow therapeutic window and requirement for frequent monitoring. Novel anticoagulants, including inhibitors of factor IIa and Xa, are currently being evaluated and may emerge as alternatives to vitamin K antagonists.

Topics: Age Factors; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Risk Factors; Stroke Volume; Thromboembolism; Vitamin K

Optimal timing for restarting anticoagulant therapy after intracranial bleeding is a critical issue. The purpose of this systematic review is to summarize published studies on the management of oral anticoagulant therapy after intracranial bleeding secondary to the use of vitamin K antagonists in patients with a mechanical heart valve. A computer-assisted search of the MEDLINE and EMBASE electronic databases till January 2008 was performed. Two investigators independently performed study selection and completed a predefined quality assessment and data extraction form. Main inclusion criterion was the enrolment of patients with a mechanical heart valve and intracranial haemorrhage during oral anticoagulant treatment. Any randomised controlled trial, observational cohort study, case series and reports was included. No randomised controlled trials were identified. Six observational cohort studies were included in the final analysis. All studies were of low quality. A total of 120 patients were enrolled. Anticoagulation was restarted within a broad time range (2 days to 3 months). Four ischaemic strokes and two recurrent cerebral haemorrhages occurred after anticoagulation was restarted after a mean follow-up of 7.9 months. Eighteen patients were described in the selected case reports. Anticoagulant therapy was restarted within four days to eight weeks. Two patients had a recurrent haemorrhagic event, and no ischaemic events were reported. In conclusion, restarting oral anticoagulant therapy few days and, indirectly, stopping anticoagulant therapy for a few days (even for 7-14 days) after the occurrence of cerebral haemorrhage are both safe. However, well-designed studies are strongly recommended to provide better evidence.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Child; Drug Administration Schedule; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Assessment; Thromboembolism; Treatment Outcome; Vitamin K

In Central Europe, the vast majority of patients with valvar heart disease today suffer from degenerative aortic valve stenosis or mitral regurgitation. Due to the aging population, the prevalence of both diseases is rapidly increasing. Despite older age at the time of intervention and more co-morbidities, perioperative mortality has been constantly low (about 3.5 % in Germany). Clinical symptoms reported by patients are often inappropriate to chose the optimal time for intervention. Myocardial contractility reserve is yet the most appropriate measure to assess myocardial adaption to the chronic pressure and/or volume overload. Awaiting myocardial maladaption is hampered by a significant worsening in prognosis. This is especially true for mitral regurgitation, where imaging techniques regularly fail to assess LV pump function due to the low left ventricular impedance. For patients with valvar heart disease requiring therapy with vitamin K antagonists, stability of oral anticoagulation therapy is essential to avoid thromboembolic as well as bleeding complications. For the majority of these patients, a target INR of 2.5 is optimal. INR point of care self management results in a more than 30 % reduction of adverse events.

Topics: Aging; Anticoagulants; Aortic Valve Stenosis; Exercise Test; Fibrinolytic Agents; Germany; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heart Valves; Humans; Mitral Valve Insufficiency; Prevalence; Prognosis; Time Factors; Vitamin K

This chapter about antithrombotic therapy in native and prosthetic valvular heart disease is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients with rheumatic mitral valve disease and atrial fibrillation (AF), or a history of previous systemic embolism, we recommend long-term oral anticoagulant (OAC) therapy (target international normalized ratio [INR], 2.5; range, 2.0 to 3.0) [Grade 1C+]. For patients with rheumatic mitral valve disease with AF or a history of systemic embolism who suffer systemic embolism while receiving OACs at a therapeutic INR, we recommend adding aspirin, 75 to 100 mg/d (Grade 1C). For those patients unable to take aspirin, we recommend adding dipyridamole, 400 mg/d, or clopidogrel (Grade 1C). In people with mitral valve prolapse (MVP) without history of systemic embolism, unexplained transient ischemic attacks (TIAs), or AF, we recommended against any antithrombotic therapy (Grade 1C). In patients with MVP and documented but unexplained TIAs, we recommend long-term aspirin therapy, 50 to 162 mg/d (Grade 1A). For all patients with mechanical prosthetic heart valves, we recommend vitamin K antagonists (Grade 1C+). For patients with a St. Jude Medical (St. Paul, MN) bileaflet valve in the aortic position, we recommend a target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A]. For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, we recommend a target INR of 3.0 (range, 2.5 to 3.5) [Grade 1C+]. For patients with caged ball or caged disk valves, we suggest a target INR of 3.0 (range, 2.5 to 3.5) in combination with aspirin, 75 to 100 mg/d (Grade 2A). For patients with bioprosthetic valves, we recommend vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) for the first 3 months after valve insertion in the mitral position (Grade 1C+) and in the aortic position (Grade 2C). For patients with bioprosthetic valves who are in sinus rhythm and do not have AF, we recommend long-term (> 3 months) therapy with aspirin, 75 to 100 mg/d (Grade 1C+).

Topics: Aspirin; Bioprosthesis; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Postoperative Complications; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Thromboembolism; Vitamin K

Systemic embolism secondary to chronic atrial fibrillation usually affect the cerebral circulation. The risk of a cerebrovascular accident in patients with chronic atrial fibrillation, irrespective of the aetiology, is 1.8 to 7.5 times that of the general population. The embolic risk is 18 times greater in patients with atrial fibrillation related to the rheumatic heart disease. The risk of patients under 60 years of age with idiopathic atrial fibrillation does not seem to be different to that of the general population. The risk of early recurrence of embolism in the first 30 days ranges from 8 to 15%. The risk of late recurrence varies but seems to be higher than that of the general population. The prognosis of embolic cerebrovascular accidents is poor with a 20% mortality rate. The benefits of preventive therapy of embolism with oral anticoagulants have been clearly established in rheumatic atrial fibrillation and in other indications. In non-valvular atrial fibrillation the benefits have to be compared with the risks of treatment. The incidence of hemorrhage due to anticoagulant therapy is between 3 and 5% per year per patient (about 1% of severe haemorrhage). Three randomised studies of primary prevention have shown a significant reduction of the embolic risk in non-valvular atrial fibrillation treated by warfarin compared to patients on placebo. Only one study has shown a significant reduction of the embolic risk in patients under 75 years of age with non-valvular atrial fibrillation treated with 325 mg/day of aspirin. However, anticoagulant therapy does not seem necessary in carefully selected patients under 60 years of age with idiopathic atrial fibrillation (less than 5% of all patients).

Topics: Aspirin; Atrial Fibrillation; Chronic Disease; Heart Valve Diseases; Humans; Primary Prevention; Prognosis; Recurrence; Risk; Thromboembolism; Vitamin K

To study in patients performing international normalized ratio (INR) self-control the efficacy and safety of an INR target range of 1.6-2.1 for aortic valve replacement (AVR) and 2.0-2.5 for mitral valve replacement (MVR) or double valve replacement (DVR).. In total, 1304 patients undergoing AVR, 189 undergoing MVR and 78 undergoing DVR were randomly assigned to low-dose INR self-control (LOW group) (INR target range, AVR: 1.8-2.8; MVR/DVR: 2.5-3.5) or very low-dose INR self-control once a week (VLO group) and twice a week (VLT group) (INR target range, AVR: 1.6-2.1; MVR/DVR: 2.0-2.5), with electronically guided transfer of INR values. We compared grade III complications (major bleeding and thrombotic events; primary end-points) and overall mortality (secondary end-point) across the three treatment groups.. Two-year freedom from bleedings in the LOW, VLO, and VLT groups was 96.3, 98.6, and 99.1%, respectively (P = 0.008). The corresponding values for thrombotic events were 99.0, 99.8, and 98.9%, respectively (P = 0.258). The risk-adjusted composite of grade III complications was in the per-protocol population (reference: LOW-dose group) as follows: hazard ratio = 0.307 (95% CI: 0.102-0.926; P = 0.036) for the VLO group and = 0.241 (95% CI: 0.070-0.836; P = 0.025) for the VLT group. The corresponding values of 2-year mortality were = 1.685 (95% CI: 0.473-5.996; P = 0.421) for the VLO group and = 4.70 (95% CI: 1.62-13.60; P = 0.004) for the VLT group.. Telemedicine-guided very low-dose INR self-control is comparable with low-dose INR in thrombotic risk, and is superior in bleeding risk. Weekly testing is sufficient. Given the small number of MVR and DVR patients, results are only valid for AVR patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Aortic Valve; Drug Administration Schedule; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Mitral Valve; Self Care; Telemedicine; Thromboembolism; Treatment Outcome; Vitamin K; Young Adult

Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Coagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin

We performed a clinical audit of maternal and fetal outcomes in pregnant women with valvular heart disease (VHD) from Portuguese-speaking African countries who were transferred for their care, during a twenty-year period, through a memorandum of agreement of international cooperation.. A retrospective analysis of 81 pregnancies in 45 patients with VHD (median age 24, interquartile range 22-29 years) from 2000 to 2020 was performed. The main outcome measures were maternal cardiovascular and fetal outcomes. History of rheumatic heart disease was present in 60 (74.1%) pregnancies. Most were in New York Heart Association (NYHA) functional class I or II; at the first evaluation, 35 (43.2%) were on cardiac medication and 49 (60.5%) were anticoagulated. Forty-eight pregnancies had at least one valvular prosthesis, including 38 mechanical heart valves. During pregnancy, deterioration in NYHA functional class occurred in 35 (42.0%), and eight (9.9%) patients required initiation or intensified cardiac medication. Mechanical valve thrombosis complicated four (4.9%) pregnancies, all cases on heparin, and resulted in one maternal death. Haemorrhagic complications happened in 7 (8.6%) anticoagulated patients, in the immediate postpartum or puerperal period. The 81 pregnancies resulted in 56 (69.1%) live births, while miscarriage and fetal malformations occurred in 19 (23.5%) and 12 (14.8%) pregnancies, respectively. In multivariate analysis, vitamin K antagonist therapy was the only independent predictor of an unsuccessful pregnancy (p = 0.048).. In a high-income country, successful pregnancy was possible with low rate of maternal events in women with VHD transferred from five low-middle income countries in Africa. The use of anticoagulation with a vitamin K antagonist was associated with an unsuccessful pregnancy.

Topics: Adult; Anticoagulants; Female; Fibrinolytic Agents; Heart Valve Diseases; Humans; Portugal; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnant Women; Retrospective Studies; Vitamin K; Young Adult

Topics: Anticoagulants; Heart Valve Diseases; Heart Valves; Humans; Vitamin K

To assess the quality of long-term anticoagulation therapy with antivitamin-K in patients with atrial fibrillation by measuring the TTR and to determine the factors associated with a good TTR.. This is an observational study conducted over a period of three years (from January 2013 until December 2015) in the outpatient clinic of cardiology of Farhat Hached hospital of Sousse, Tunisia. Pre-established individual plugs were used for data collection. The data analysis was performed using the SPSS Software, version 20.. Overall, 200 patients were eligible. Half of the patients did not know the risks of AVK and 29.1% were unaware of their interest. The average TTR was 57.3±18.2%. Good control of anticoagulation was obtained in 24.5% of patients. Those with a≥70% were more autonomous, observant, of urban origin, living in Sousse and Kairouan, with good knowledge about AVK and having a small left atrium. The factors associated negatively with TTR were hypertension, diabetes, old AF, hematological diseases, high number of medications taken daily and the presence of mitral insufficiency, mitral valve replacement, a tricuspid insufficiency or a tricuspid plasty.. The quality of AVK anticoagulation in AF patients is insufficient. Improving this indicator would reduce the morbidity and mortality associated with AVK treatment.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Diabetic Angiopathies; Female; Health Knowledge, Attitudes, Practice; Heart Valve Diseases; Hematologic Diseases; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Male; Middle Aged; Polypharmacy; Quality of Health Care; Risk Factors; Thromboembolism; Thrombolytic Therapy; Tunisia; Vitamin K

Management strategies for patients with atrial fibrillation (AF) in association with valvular heart disease (VHD) have been less informed by randomized trials, which have largely focused on ‘non-valvular AF’ patients. Thromboembolic risk also varies according to valve lesion and may also be associated with CHA2DS2-VASc score risk factor components, rather than only the valve disease being causal.\ \ Given the need to provide expert recommendations for professionals participating in the care of patients presenting with AF and associated VHD, a task force was convened by the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group (WG) on Thrombosis, with representation from the ESC WG on Valvular Heart Disease, Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE) with the remit to comprehensively review the published evidence, and to produce a consensus document on the management of patients with AF and associated VHD, with up-to-date consensus statements for clinical practice for different forms of VHD, based on the principles of evidence-based medicine.\ \ This is an executive summary of a consensus document which proposes that the term ‘valvular AF’ is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional EHRA (Evaluated Heartvalves, Rheumatic or Artificial) categorization in relation to the type of OAC use in patients with AF, as follows: (1) EHRA (Evaluated Heartvalves, Rheumatic or Artificial) type 1 VHD, which refers to AF patients with ‘VHD needing therapy with a vitamin K antagonist (VKA)’ and (2) EHRA (Evaluated Heartvalves, Rheumatic or Artificial) type 2 VHD, which refers to AF patients with ‘VHD needing therapy with a VKA or a non-VKA oral anticoagulant also taking into consideration CHA2DS2-VASc score risk factor components.

Topics: Administration, Oral; Africa, Southern; Asia; Atrial Fibrillation; Europe; Evidence-Based Medicine; Expert Testimony; Fibrinolytic Agents; Heart Valve Diseases; Humans; Latin America; Practice Guidelines as Topic; Risk; Stroke; Vitamin K

Guidelines generally recommend oral anticoagulation to be considered the first 3 months after mitral valve repair based on small studies and consensus. However, in several studies no benefit of anticoagulation has been found.. From the national registries we identified all Danish patients who underwent mitral valve repair during the period between 1997 and 2012. Medication, hospitalisation and mortality data were studied. The association of use of vitamin K antagonists (VKAs) at discharge and risk of stroke/death was evaluated by means of Cox regression, landmark analyses and propensity matched models.. 2188 patients without prior VKA use, stroke or death day 7 after discharge were included and median follow-up was 4.9 years (0-13.7). 859 (39%) were discharged on VKAs and 523 (24%) experienced death or stroke, 60 of these occurred within the first 3 months and 24 between 3 and 6 months. Compared with patients without post-discharge VKA, patients on VKA had a lower risk of death/stroke at 3 months (HR=0.28, CI (0.13 to 0.62), p=0.002) and in the time period from 3 to 6 months (HR=0.85, CI (0.35 to 2.07), p=0.72). Risk of significant bleeding complications within 3 months were comparable in the two groups with 23 (2%) among patients without VKA and 6 (1%) among VKA-treated.. VKA treatment after mitral valve repair is associated with a markedly lower risk of adverse events as stroke or death without excess major bleeding risk during the first 3 months following surgery.

Topics: Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitral Valve; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Stroke; Vitamin K; Young Adult

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Time in Therapeutic Range (TTR) is a value used to assess the efficacy of Warfarin treatment. The aim of our study is to determine the effective INR levels and the rate of TTR in patients on Warfarin regimen due to Atrial Fibrillation (AF) or Mechanical Prosthetic Valve (MPV). A total of 94 patients (58 female, and 36 male, mean age: 64.9±11years) on Warfarin treatment due to AF or MPV with at least 10 INR levels measurements in the last 6 months were included in this retrospective study. The patients were divided into 2 groups. Group 1 consisted of the patients with Valvular AF (n=47); Group 2 included the patients with Non-Valvular AF (n=47); TTR and INR levels were compared. The average of INR values were found as 2,4 (min: 1,3, max: 4,3) in all patients; 2,3 (min: 1,3, max: 4,2) in Group 1; 2,6 (min: 1,3, max: 4,3) in Group 2. The average of TTR values was found 40.3% (min: 10%, max: 80%) in all patients; 43.8% (min: 10%, max: 80%) in Group 1; 36,8% (min: 10%, max: 80%) in Group 2. INR and TTR values are needed to assess the effectiveness of the Warfarin treatment. The patients in treatment with Warfarin should be well trained and frequently monitored. On the other hand, the underlying factors of the TTR values being determined as lower in the Turkish patient population might be due to the lower socio-economic and socio-cultural status, inadequate education levels, and the insufficient information on use of the medication provided by the doctors to the patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin

The study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).. Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.. A multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (n = 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.. During a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; p = 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; p = 0.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; p = 0.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (n = 463) were evaluated.. In TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Atrial Fibrillation; Brain Ischemia; Canada; Chi-Square Distribution; Europe; Female; Heart Valve Diseases; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K; Warfarin

Renal infarction is an uncommon and underdiagnosed cause of acute flank pain. We describe a 48-year-old male patient, previously diagnosed with a bicuspid aortic valve, who presented with multiple renal infarctions, secondary to multiple dissections of the aberrant renal vascular anatomy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aortic Dissection; Aortic Valve; Bicuspid Aortic Valve Disease; Drug Therapy, Combination; Follow-Up Studies; Funnel Chest; Heart Valve Diseases; Heparin, Low-Molecular-Weight; Humans; Infarction; Kidney; Male; Middle Aged; Renal Artery; Renal Circulation; Risk Factors; Treatment Outcome; Vitamin K

Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered.. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C).. These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Topics: Aspirin; Catheterization; Combined Modality Therapy; Ductus Arteriosus, Patent; Evidence-Based Medicine; Fibrinolytic Agents; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Platelet Aggregation Inhibitors; Postoperative Complications; Rheumatic Heart Disease; Risk Factors; Societies, Medical; Stroke; Thromboembolism; Thrombolytic Therapy; Thrombosis; Vitamin K

Despite the high prevalence and clinical importance of atrial fibrillation (AF), there is no Brazilian study describing the clinical profile of patients with AF and the most used treatment strategy (rhythm control vs. rate control).. Assess the most common treatment on AF in an outpatient specialized clinic for management of AF. In addition, the clinical profile of the population studied was provided.. Cross-sectional study assessing the most used strategy for atrial fibrillation control in 167 patients. The clinical profile was also described. A standardized form was used for data collection and statistical analysis was performed by SPSS 13.0 software.. In This high risk population for thromboembolic events (61% had CHADS(2) ≥ 2), 54% of patients had paroxysmal or persistent AF, 96.6% were on vitamin K antagonists or acetylsalicylic acid, and 76.6% on beta-blocker (rate control 81,2% x rhythm control 58,8%; p < 0.05). Heart rate control was the most used strategy (79.5% x 20.5%; p < 0.001). A statistical tendency towards more patients with ventricular dysfunction (15.2% x 2.9%; p = 0.06), CHADS(2) ≥ 2 (60.5% x 39.5%; p = 0.07) and heart valve diseases (25.8% x 11.8%; p = 0.08) was observed in the heart rate control group.. In this high risk population for thromboembolic events, the rate control strategy was the most used.

Topics: Adrenergic beta-Antagonists; Aged; Ambulatory Care; Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Brazil; Epidemiologic Methods; Female; Heart Conduction System; Heart Rate; Heart Valve Diseases; Humans; Male; Thromboembolism; Ventricular Dysfunction, Left; Vitamin K

Current American Heart Association/American College of Cardiology guidelines recommend anticoagulation and antiplatelet therapy during the first 90 postoperative days; however, there is wide variability in the administration of antithrombotic therapy after bioprosthetic aortic valve replacement. We sought to determine whether early antithrombotic therapy was necessary in patients undergoing isolated bioprosthetic aortic valve implantation and who were discharged in normal sinus rhythm.. From December 2001 to October 2008, 1131 patients underwent isolated bioprosthetic aortic valve implantation at Brigham and Women's Hospital. After exclusion of patients who underwent concomitant operations (n = 138, 12%), patients who were anticoagulated preoperatively (n = 4, 0.4%), and patients who experienced postoperative refractory atrial fibrillation requiring anticoagulation at discharge (n = 128, 11%), our study base consisted of 861 patients. Patients were followed for 90 days postoperatively for the occurrence of thromboembolism, including stroke, transient ischemic attack, or peripheral thromboembolic events and bleeding complications.. Of the 861 patients included in this study, 133 (15%) were anticoagulated with warfarin sodium (AC+) postoperatively and 728 (85%) were not (AC-). Patients who received postoperative anticoagulation were older; had a higher incidence of hypertension, cerebrovascular accident, and pulmonary vascular disease; and were more symptomatic at presentation. The 90-day risk of thromboembolism (cerebrovascular accident, transient ischemic attack, or peripheral thromboembolism) after surgery was 5% (n = 6) in those who were anticoagulated and 5% (n = 39) in those who were not (P = .67). Independent predictors of thromboembolism were found to be increasing age (odds ratio, 1.03; P = .03), female gender (odds ratio, 2.23; P = .005), short stature (odds ratio, 0.97; P = .002), smoking status (P = .05), New York Heart Association III/IV (odds ratio 1.77, P = .04), and a 19-mm bioprosthetic aortic valve prosthesis (odds ratio, 2.22; P = .03). Evaluation of each predictor with postoperative acetylsalicylic acid+ and AC+ interaction terms revealed that female patients (odds ratio, 0.75; P = .03 AC+; odds ratio, 0.66; P = .02 acetylsalicylic acid+) and patients with a 19-mm bioprosthetic aortic valve (odds ratio, 0.65; P = .02 AC+; odds ratio, 0.36; P = .01 acetylsalicylic acid+) had a reduction in the incidence of thromboembolism when administered acetylsalicylic acid or warfarin sodium. Patients who were in New York Heart Association III/IV also had a reduction of thromboembolism when given vitamin K antagonist (odds ratio, 0.73; P = .04); a similar trend was observed in patients given acetylsalicylic acid (odds ratio, 0.34; P = .06).. Early anticoagulation after isolated bioprosthetic aortic valve replacement in patients in normal sinus rhythm does not seem to reduce the risk of thromboembolism except in high-risk groups. Current recommendations should be revisited, because the only patients who may benefit from anticoagulation are female, those who are highly symptomatic, and those with a small aortic prosthesis.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aspirin; Bioprosthesis; Chi-Square Distribution; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Odds Ratio; Patient Selection; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Patients with prosthetic heart valves have a higher risk of developing valve thrombosis and arterial thromboembolism. Antithrombotic therapy during the early postoperative period after biologic mitral valve replacement (MVR) is controversial. Hence, a retrospective study was conducted to investigate the efficacy of different antithrombotic therapies in patients after MVR with bioprostheses.. Between January 2000 and January 2006, a total of 99 patients presenting with preoperative sinus rhythm underwent isolated bioprosthetic MVR. Of these patients, 59 (58%) received a bovine pericardial xenograft, and 40 (42%) a porcine bioprosthesis. The postoperative antithrombotic therapy was prescribed according to the surgeon's preference.. Fifty-one (51%) patients received acetylsalicylic acid (ASA group, 100 mg/day), 12 (13%) did not receive any specific antithrombotic therapy (NT group), and 36 (36%) received a vitamin K antagonist (VKA group, INR 2-3). The primary endpoints were the rate of cerebral ischemic events, bleeding events, and survival. The mean follow up was 23 months (range: 3-68 months). There were five early deaths (5%), and eight late deaths (8%). There were five episodes of cerebral ischemic events; these included three patients (8.3%) in the VKA group, one patient (2.0%) in ASA group, and one patient (8.3%) in the NT group (p = 0.351). Of these episodes, two occurred between 24 h and three months after surgery. Only one (2.8%) episode of major bleeding occurred (in the VKA group), due to poor anticoagulation management.. Each of the antithrombotic therapies evaluated appeared to be safe. There was no evidence to suggest that any specific antithrombotic therapy would be superior in preventing valve thrombosis in patients undergoing bioprosthetic MVR.

Topics: Aged; Aged, 80 and over; Animals; Anticoagulants; Aspirin; Bioprosthesis; Brain Ischemia; Cattle; Chi-Square Distribution; Drug Administration Schedule; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Mitral Valve; Practice Guidelines as Topic; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Swine; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Animals; Anticoagulants; Aortic Valve; Biomarkers; Calcinosis; Calcium-Binding Proteins; Chronic Disease; Down-Regulation; Extracellular Matrix Proteins; Glomerular Filtration Rate; Heart Valve Diseases; Humans; Kidney Diseases; Matrix Gla Protein; Prognosis; Vascular Diseases; Vitamin K

Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 +/- 123.1 nM) compared to the control group (571.6 +/- 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Animals; Anticoagulants; Aorta; Aortic Valve; Biomarkers; Calcinosis; Calcium-Binding Proteins; Case-Control Studies; Cross-Sectional Studies; Disease Models, Animal; Down-Regulation; Echocardiography; Extracellular Matrix Proteins; Female; Glomerular Filtration Rate; Heart Valve Diseases; Humans; Male; Matrix Gla Protein; Mice; Mice, Inbred DBA; Middle Aged; Osteopontin; Prognosis; Risk Assessment; Risk Factors; RNA, Messenger; Severity of Illness Index; Time Factors; Tomography, Spiral Computed; Vitamin K; Warfarin

Low international normalized ratio (INR;

Topics: Aged; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Valve Diseases; Humans; International Normalized Ratio; Male; Medication Adherence; Prospective Studies; Risk Factors; Sex Factors; United States; Venous Thromboembolism; Vitamin K; Warfarin

This chapter about antithrombotic therapy for valvular heart disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values might lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with rheumatic mitral valve disease complicated singly or in combination by the presence of atrial fibrillation (AF), previous systemic embolism, or left atrial thrombus, we recommend vitamin K antagonist (VKA) therapy (Grade 1A). For patients with rheumatic mitral valve disease and normal sinus rhythm, without left atrial enlargement, we do not suggest antithrombotic therapy unless a separate indication exists (Grade 2C). For patients with mitral valve prolapse (MVP), not complicated by AF, who have not had systemic embolism, unexplained transient ischemic attacks, or ischemic stroke, we recommend against antithrombotic therapy (Grade 1C). In patients with mitral annular calcification complicated by systemic embolism or ischemic stroke, we recommend antiplatelet agent (APA) therapy (Grade 1B). For patients with isolated calcific aortic valve disease, we suggest against antithrombotic therapy (Grade 2C). But, for those with aortic valve disease who have experienced ischemic stroke, we suggest APA therapy (Grade 2C). For patients with stroke associated with aortic atherosclerotic lesions, we recommend low-dose aspirin (ASA) therapy (Grade 1C). For patients with cryptogenic ischemic stroke and a patent foramen ovale (PFO), we recommend APA therapy (Grade 1A). For patients with mechanical heart valves, we recommend VKA therapy (Grade 1A). For patients with mechanical heart valves and history of vascular disease or who have additional risk factors for thromboembolism, we recommend the addition of low-dose aspirin ASA to VKA therapy (Grade 1B). We suggest ASA not be added to long-term VKA therapy in patients with mechanical heart valves who are at particularly high risk of bleeding (Grade 2C). For patients with bioprosthetic heart valves, we recommend ASA (Grade 1B). For patients with bioprosthetic heart valves and additional risk factors for thromboembolism, we recommend VKA therapy (Grade 1C). For patients with infective

Topics: Aspirin; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Diseases; Humans; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Vitamin K

Transesophageal echocardiography (TEE) has been used to document the incidence of non-obstructive thrombosis (NOT) after mechanical prosthetic mitral valve replacement (MVR). The postoperative occurrence and unpredictable evolution of NOT complicate its management. The study aim was to examine the safety and efficacy of prolonged, combined administration of heparin and vitamin K antagonists (VKA) recommended for this indication.. All patients who underwent mechanical prosthetic MVR between July 1999 and December 2004 at the authors' institution were systematically studied with TEE immediately after surgery. Patients who presented with > or = 5 mm NOT were treated with combined heparin and VKA until TEE-confirmed resolution of the thrombus.. Among 256 patients who underwent 263 MVRs (seven reinterventions), 47 (17.9%) presenting with > or = 5 mm NOT received combined heparin and VKA for between 7 and 115 days (median 17 days). No thromboembolic or hemorrhagic events or deaths were observed during this period of observation. Four patients were treated with danaparoid and VKA because of thrombocytopenia induced by heparin before the diagnosis of NOT. Over a mean follow up of 39 months, one patient died from cancer and another from the sequelae of a stroke. In total, there were five NOT recurrences, three of which were complicated by embolic events without sequelae within eight months, and one by a recurrent stroke. In addition, three patients without demonstrable NOT recurrence suffered transient ischemic attacks.. Among this small sample of patients, combined heparin and VKA was well tolerated and effective, and could prevent reoperation or thrombolysis. These observations may warrant further study in a larger patient population.

Topics: Adult; Aged; Anticoagulants; Cause of Death; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Long-Term Care; Male; Middle Aged; Mitral Valve; Postoperative Complications; Stroke; Thrombosis; Vitamin K

Low-molecular-weight heparin (LMWH) is considered a recommended anticoagulation option in pregnant women with prosthetic heart valves. However, few data are available regarding the efficacy and safety of LMWH in this setting.. In 1999, the authors' institution developed a standardized anticoagulation protocol for pregnant women with prosthetic heart valves, which included LMWH administered between six and 12 weeks' gestation, and after 36 weeks, with prespecified target levels, and additional low-dose aspirin. Herein is presented the initial experience using this anticoagulation regimen.. Among five women with prosthetic heart valves treated with LMWH during part of their pregnancy, four had uneventful pregnancies while one suffered a coronary artery embolus. A review is provided of the current state of knowledge regarding anticoagulation in pregnancy, with emphasis placed on the importance of strict monitoring of anticoagulation levels.. Given the drawbacks of other forms of anticoagulation, and within the constraints of available data, LMWH appears--when administered with caution--to be an acceptable alternative in pregnant women with prosthetic heart valves.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Aspirin; Biomarkers; Coronary Artery Disease; Drug Therapy, Combination; Embolism; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Mitral Valve; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular; Quebec; Treatment Outcome; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Transfusion; Cardiopulmonary Bypass; Factor XII Deficiency; Heart Transplantation; Heart Valve Diseases; Heparin; Heparin Antagonists; Humans; Indenes; Male; Mitral Valve; Monitoring, Intraoperative; Plasma; Protamines; Vitamin K; Whole Blood Coagulation Time

Transoesophageal echocardiography has shown a high incidence on non-obstructive thrombosis after mitral valve replacement with a mechanical prosthesis. The unpredictable outcome and the period during which the complication arises make treatment difficult. The aim of this study was to assess the tolerance and efficacy of the association of long-term heparin and oral anticoagulation, as recommended in this indication. All patients undergoing mitral valve replacement with a mechanical prosthesis between June 1999 and July 2001 were systematically included and studied by transoesophageal echocardiography in the immediate postoperative period. Those with non-obstructive thrombosis at least 5 mm in size were treated by heparin and oral coagulation until the thrombus disappeared on transoesophageal echocardiography. One hundred and fourteen patients undergoing 120 mitral valve replacements (6 reoperations) underwent transoesophageal echocardiography and non-obstructive thrombi measuring at least 5 mm were found on 26 occasions (21.7%). The association of heparin and oral coagulation was maintained for 7 to 115 days (average 20 days). No thromboembolic or haemorrhagic complications and no deaths were observed during this period. Two patients were treated with danaparoid and oral anticoagulation because of heparin-induced thrombocytopenia before the diagnosis. None of the patients died during follow-up (average 49 months); there were 4 recurrent non-obstructive thromboses, three of which were complicated by thromboembolic events with no sequellae in the first 8 months, again treated effectively with the association of heparin and oral anticoagulants; two cerebral embolic events without sequellae were observed without a demonstrable non-obstructive thrombus on transoesophageal echocardiography. The authors conclude that the association of heparin and oral anticoagulants seems well tolerated and effective in this small population and this would justify a large scale clinical trial.

Topics: Adult; Aged; Anticoagulants; Aspirin; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Male; Middle Aged; Mitral Valve; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Drug Administration Schedule; Heart Valve Diseases; Humans; Indenes; Myocardial Infarction; Thromboembolism; Vitamin K

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Chemoprevention; Drug Monitoring; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Myocardial Infarction; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

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

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.

Topics: Animals; Arteries; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Valve Diseases; Male; Matrix Gla Protein; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Tests; Heart Valve Diseases; Heparin; Humans; Mitral Valve; Thromboembolism; Vitamin K

The pathogenesis of valvar calcification, which complicates the course of cardiac valve disease and also affects tissue valve prostheses, is incompletely understood. The present work explores the possible role of the vitamin K-dependent, calcium-binding amino acid, gamma-carboxyglutamic acid (Gla) in valve mineralization. Gla is normally found in the vitamin K-dependent clotting factor proteins, and is also present in unique calcium binding proteins in bone, kidney, and lung. Unique Gla-containing proteins have also been isolated from pathologic calcifications including calcium containing renal stones and calcified atherosclerotic plaque. Calcified valves including specimens with calcific aortic stenosis, calcified porcine xenograft valves, and a calcified aortic homograft valve were analyzed for Gla content, complete amino acid analysis, and tissue calcium and phosphorus levels. Normal porcine valves contained protein-bound Gla (2.0-10.6 Gla/10(4) amino acids): no Gla was present in normal valve leaflets. Furthermore, Gla levels paralleled tissue calcium content in the calcified valves. In addition, complete amino acid analysis indicated a decline in valvar collagen content plus increased acidic proteins in conjunction with valvar calcification and the presence of Gla-containing proteins. These results suggest that calcific valvar disease may result in part from vitamin K-dependent processes.

Topics: 1-Carboxyglutamic Acid; Animals; Aortic Valve; Aortic Valve Stenosis; Bioprosthesis; Calcinosis; Calcium-Binding Proteins; Heart Valve Diseases; Humans; Transplantation, Homologous; Vitamin K

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation Tests; Child; Female; Heart Valve Diseases; Heart Valve Prosthesis; Hemodynamics; Hemolysis; Heparin; Humans; Male; Middle Aged; Mitral Valve; Postoperative Complications; Sepsis; Thromboembolism; Vitamin K