scholarly journals Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

2015 ◽  
Vol 9 (4) ◽  
pp. 314
Author(s):  
Tommaso Sacquegna ◽  
Anna Zaniboni ◽  
Andrea Rubboli ◽  
Gaetano Procaccianti ◽  
Michela Crisci ◽  
...  

Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF), with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (<em>i.e</em>., dabigatran) and direct factor Xa inhibitors (<em>i.e</em>., apixaban and rivaroxaban) have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke) subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.


Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Tan Ru San ◽  
Mark Yan Yee Chan ◽  
Teo Wee Siong ◽  
Tang Kok Foo ◽  
Ng Kheng Siang ◽  
...  

Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)—direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban—do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)—the RE-LY, ROCKET AF, and ARISTOTLE trials—demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.


2021 ◽  
Vol 96 (4) ◽  
pp. 296-311
Author(s):  
Ki Hong Lee ◽  
Jin-Bae Kim ◽  
Seung Yong Shin ◽  
Boyoung Joung

Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.


2016 ◽  
Vol 29 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Sandeep Devabhakthuni ◽  
Connie H. Yoon ◽  
Kathleen J. Pincus

Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.


Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.


Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.


2011 ◽  
Vol 106 (11) ◽  
pp. 868-876 ◽  
Author(s):  
Luciano Crippa ◽  
Anna Falanga ◽  
Guido Finazzi ◽  
Francesco Marongiu ◽  
Gualtiero Palareti ◽  
...  

SummaryDabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.


2021 ◽  
Vol 10 (15) ◽  
pp. 3212
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Laura Piccioni ◽  
Carmelo Massimiliano Rao ◽  
...  

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.


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