Oral anticoagulant treatment: friend or foe in cardiovascular disease?

Blood ◽  
2004 ◽  
Vol 104 (10) ◽  
pp. 3231-3232 ◽  
Author(s):  
Leon J. Schurgers ◽  
Hermann Aebert ◽  
Cees Vermeer ◽  
Burkhard Bültmann ◽  
Jan Janzen
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin K ◽  
Heart Valves ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Arterial Calcification ◽  
Adverse Side Effect ◽  
Oral Anticoagulant Treatment ◽  
Carboxyglutamic Acid

Abstract Calcification is a common complication in cardiovascular disease and may affect both arteries and heart valves. Matrix γ-carboxyglutamic acid (Gla) protein (MGP) is a potent inhibitor of vascular calcification, the activity of which is regulated by vitamin K. In animal models, vitamin K antagonists (oral anticoagulants [OACs]) were shown to induce arterial calcification. To investigate whether long-term OAC treatment may induce calcification in humans also, we have measured the grade of aortic valve calcification in patients with and without preoperative OAC treatment. OAC-treated subjects were matched with nontreated ones for age, sex, and disease. Calcifications in patients receiving preoperative OAC treatment were significantly (2-fold) larger than in nontreated patients. These observations suggest that OACs, which are widely used for antithrombotic therapy, may induce cardiovascular calcifications as an adverse side effect.

Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification

2009 ◽  
Vol 101 (04) ◽  
pp. 706-713 ◽  
Author(s):  
Thilo Krueger ◽  
Ralf Westenfeld ◽  
Harald Peter Kühl ◽  
Vincent Brandenburg ◽  
Andreas Horst Mahnken ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Reference Population ◽  
Matrix Gla Protein ◽  
Control Group ◽  
Adverse Side Effect ◽  
Dependent Protein ◽  
Local Expression

SummaryMatrix-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.

New oral anticoagulants in development

2010 ◽  
Vol 103 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Jeffrey Weitz
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Dietary Vitamin ◽  
Multiple Drug ◽  
Coagulation Monitoring ◽  
Advanced Stages

SummaryAlthough currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low-molecular-weight heparins and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.

The new oral anticoagulants

Blood ◽  
2010 ◽  
Vol 115 (1) ◽  
pp. 15-20 ◽  
Author(s):  
David Garcia ◽  
Edward Libby ◽  
Mark A. Crowther
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Clinical Trial Data ◽  
Therapeutic Index ◽  
Intrapatient Variability ◽  
Coronary Syndromes ◽  
Late Stages ◽  
Anticoagulant Medication

Abstract Although their first application in clinical practice occurred in the 1940s, vitamin K antagonists remain the only form of oral anticoagulant medication approved for long-term use. Although the available vitamin K antagonists are highly effective for the prevention and/or treatment of most thrombotic disease, the significant interpatient and intrapatient variability in dose-response, the narrow therapeutic index, and the numerous drug and dietary interactions associated with these agents have led clinicians, patients, and investigators to search for alternative agents. Three new orally administered anticoagulants (apixaban, dabigatran, and rivaroxaban) are in the late stages of development and several others are just entering (or moving through) earlier phases of investigation. These novel anticoagulant medications are being studied for the prevention and treatment of venous thromboembolism, the treatment of acute coronary syndromes and the prevention of stroke in patients with atrial fibrillation. This review summarizes published clinical trial data pertinent to apixaban, dabigatran, and rivaroxaban.

scholarly journals Treatment with new oral anticoagulants in the family medicine practice

2015 ◽  
Vol 10 (4) ◽  
pp. 329-332
Author(s):  
Camelia DIACONU ◽  
◽  
Giorgiana DEDIU ◽  
Mădălina ILIE ◽  
Mihaela Adela IANCU ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Rapid Onset ◽  
New Oral Anticoagulants ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Rapid Clearance ◽  
Concomitant Medications

Vitamin K antagonists represented for more than 50 years the only oral anticoagulant treatment option, though encumbered by numerous food and drug interactions, with direct impact on the safety and efficacy of this treatment. The frequent complications of anticoagulant treatment with vitamin K antagonists led to the need for the emergence of new oral anticoagulants (NOAC). The main NOACs used today are dabigatran, rivaroxaban and apixaban. NOAC have a number of advantages over antivitamin K anticoagulants: fewer drug interactions, no food interactions, rapid onset of the anticoagulant action, rapid clearance, no need for INR monitoring. NOAC therapy must be individualized according to patient age, comorbidities and medical history, renal function, concomitant medications. Given that clinical experience with NOAC is still limited in practice, physicians (including family physicians) must monitor these patients and need to pay attention and report any side effects.

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.

Direct Oral Anticoagulants and the Paradigm Shift in the Management of Venous Thromboembolism

2018 ◽  
Vol 44 (03) ◽  
pp. 261-266 ◽  
Author(s):  
Hui Yin Lim ◽  
Harshal Nandurkar ◽  
Prahlad Ho
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Management ◽  
Real World Data ◽  
Risk Assessment Models

AbstractThe advent of direct oral anticoagulants (DOACs) has revolutionized anticoagulation management in both stroke prevention and venous thromboembolism (VTE) treatment/prevention. Clinical trials and secondary real-world data have shown that DOACs have similar efficacy and, in some cases, improved bleeding safety profiles compared with vitamin K antagonists. Together with benefits of patient convenience, this has shifted the risk–benefit ratio toward long-term anticoagulation. However, current VTE risk assessment models are based on vitamin K antagonists and do not take into account the new paradigm of DOACs. Therefore, challenges to the thrombosis community remain to determine patients who would benefit from long-term anticoagulation in the DOAC era. Here, the authors review the current literature on risks and benefits of DOACs and their potential role in long-term VTE thromboprophylaxis as well as in current risk assessment models. The increasing use of DOACs, led by their convenience of use and generally lower bleeding rates, calls for a reevaluation of the current models as the benefits of long-term anticoagulation may begin to outweigh risks and inconvenience associated with their predecessors.

scholarly journals Epidemiological data on the use of traditional anticoagulants in cardiovascular disease

ESC CardioMed ◽  
2018 ◽  
pp. 281-288
Author(s):  
Christina Reith ◽  
Colin Baigent
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Venous Thromboembolism ◽  
Heart Valves ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Epidemiological Data ◽  
Prosthetic Heart Valves ◽  
Coronary Syndrome

Traditional anticoagulants (e.g. parenteral heparins and oral vitamin K antagonists such as warfarin (coumadin), acenocoumarol, dicoumarol, phenprocoumon, phenindione, and fluindione) are widely used, including in coronary heart disease, atrial fibrillation, prosthetic heart valves, and heart failure, and as prophylaxis and treatment for venous thromboembolism. The parenteral anticoagulants are typically used in acute coronary syndrome, as initial treatment for venous thromboembolism, or as bridging therapy perioperatively, while the oral anticoagulants form the mainstay of traditional anticoagulant therapy for other indications.

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