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

Abstract

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

Validation of a Modified CHA 2 DS 2 -VASc Score for Stroke Risk Stratification in Asian Patients With Atrial Fibrillation

“…8 The treatment threshold with vitamin K antagonist may even be lower with good quality anticoagulation control, where a high time in therapeutic range (>70%) is achieved, given that a high time in therapeutic range is associated with best efficacy and safety related to vitamin K antagonists. [22][23][24] All clinical risk scoring systems have broadly comparable predictive value for identifying high-risk patients who sustain stroke events. Rather than a categorized approach to stroke risk stratification focusing on high-risk patients, a simple approach to thromboprophylaxis is to initially identify truly low-risk patients in whom OACs could be clearly omitted.…”

Relationship of Age With Stroke and Death in Anticoagulated Patients With Nonvalvular Atrial Fibrillation

“…15 Thus, effective stroke prevention in various guidelines with oral anticoagulants refers to the use of well-controlled warfarin (TTR≥70%) or non-VKA oral anticoagulants. 16,17 A recent European Society of Cardiology position article 16 also recommended the use of new SAMe-TT 2 R 2 (sex female, age <60 years, medical history [more than two comorbidities], treatment [interacting drugs], tobacco use [doubled], race [doubled]) score to help decision making by identifying patients with AF expected to do well on warfarin (SAMe-TT 2 R 2 score, 0-1) or those likely to have poor anticoagulation control (SAMe-TT 2 R 2 score, >2). 18,19 Nonetheless, being elderly also requires additional attention in terms of impaired cognitive function 20 and frailty.…”

Comparison of the Abilities of Summary Measures of International Normalized Ratio Control to Predict Clinically Relevant Bleeding

“…For example, the European Society of Cardiology position article recommends that if a TTR of 70% cannot be attained, consideration should be given to using therapies other than a vitamin K antagonist. 25 Our results suggest that judging the adequacy of vitamin K antagonist therapy by TTR alone may be insufficient and that other parameters may play a role, such as INR variability.…”