The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation

2020 ◽  
Vol 225 ◽  
pp. 69-77 ◽  
Author(s):  
Ganesan Karthikeyan ◽  
Stuart J Connolly ◽  
Mpiko Ntsekhe ◽  
Alexander Benz ◽  
Sumathy Rangarajan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Randomized Trial ◽  
Vitamin K ◽  
Research Program ◽  
Vitamin K Antagonists ◽  
Disease Research ◽  
Baseline Characteristics ◽  
Rheumatic Valvular Disease ◽  
Rheumatic Heart

Vitamin K antagonists in heart disease: Current status and perspectives (Section III)

2013 ◽  
Vol 110 (12) ◽  
pp. 1087-1107 ◽  
Author(s):  
Raffaele Caterina ◽  
Steen Husted ◽  
Lars Wallentin ◽  
Felicita Andreotti ◽  
Harald Arnesen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Vitamin K ◽  
Heart Valves ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Coagulation Factors ◽  
Current Status ◽  
Cardiovascular Therapy ◽  
Specific Disorders

SummaryOral 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.

New Drugs for Thromboembolic Prevention in Atrial Fibrillation

2010 ◽  
Vol 6 (4) ◽  
pp. 64
Author(s):  
Jose L Merino ◽  
Jose López-Sendón ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Negative Impact ◽  
Vitamin K Antagonists ◽  
Coagulation Factor ◽  
Developed Countries ◽  
New Drugs ◽  
Risk Scores ◽  
Bleeding Events ◽  
Risk Patients

Atrial fibrillation (AF) is the most frequent sustained arrhythmia and its prevalence is increasing in developed countries. This progressive increase and the negative impact of this arrhythmia on the patient’s prognosis make AF one of the main healthcare problems faced today. This has led to intense research into the main aspects of AF, one of them being thromboembolism prevention. AF patients have a four to five times higher risk of stroke than the general population. Several factors increase thromboembolic risk in patients with AF and the use of risk scores, such as the Congestive Heart Failure, Hypertension, Age Greater than 75, Diabetes, and Prior Stroke or Transient Ischemic Attack (CHADS2), have been used to identify the best candidates for anticoagulation. Antithrombotic drugs are the mainstay of therapy for embolic prevention. The clinical use of these drugs is based on the risk–benefit ratio, where benefit is the reduction of stroke and systemic embolic events and risk is mostly driven by the increase in bleeding events. Generally, antiplatelets are indicated for low-risk patients in light of the fact anticoagulants are the drug of choice for moderate- or high-risk patients. Vitamin K antagonists have been the only option for oral anticoagulation for the last 50 years. However, these drugs have many pharmacodynamic and pharmacokinetic problems. The problems of anticoagulation with vitamin K antagonists have led to the investigation of new drugs that can be administered orally and have a better dose–response relationship, a shorter half-life and, in particular, higher efficacy and safety without the need for frequent anticoagulation controls. The drugs that have been studied most thoroughly in patients with AF are inhibitors of the activated coagulation factor X and inhibitors of coagulation factor II (thrombin), including ximelagatran and dabigatran. In addition, non-pharmacological therapies have been developed to prevent recurrent embolism in certain patient populations.

scholarly journals Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

2021 ◽  
Vol 10 (15) ◽  
pp. 3212
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Laura Piccioni ◽  
Carmelo Massimiliano Rao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Advance ◽  
Thromboembolic Events ◽  
Thromboembolic Risk ◽  
Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

scholarly journals The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

2020 ◽  
Vol 18 (1) ◽  
pp. 137
Author(s):  
Kuang-Tsu Yang ◽  
Wei-Chih Sun ◽  
Tzung-Jiun Tsai ◽  
Feng-Woei Tsay ◽  
Wen-Chi Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Optimal Dosage

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535–0.748; p < 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs.

scholarly journals Comparison of Left Atrial Appendage Occlusion versus Non-Vitamin-K Antagonist Oral Anticoagulation in High-Risk Atrial Fibrillation: An Update

2021 ◽  
Vol 8 (6) ◽  
pp. 69
Author(s):  
Shaojie Chen ◽  
K. R. Julian Chun ◽  
Zhiyu Ling ◽  
Shaowen Liu ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
High Risk ◽  
Vitamin K ◽  
Major Bleeding ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Vitamin K Antagonists ◽  
Left Atrial Appendage Occlusion ◽  
The Mean

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.

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