A recently published review analyzed data from multiple studies on the efficacy and safety of a new drug class for the treatment of atrial fibrillation and venous thromboembolism, the non-vitamin K antagonist oral anticoagulant (NOAC). It concluded that the NOAC was superior or comparable to existing vitamin K antagonist drugs (warfarin) for the treatment of these disorders.
Atrial fibrillation, a condition characterized by an irregular and often rapid beating of the heart, increases your chances of blood clots, strokes, and heart failure. Venous thromboembolism is a potentially fatal vascular condition that involves the formation and transport of clots in the veins; if these clots travel to the lungs, they may block blood supply and cause vessel damage. To reduce the chances of blood clotting, people with this condition are prescribed blood thinners. Warfarin is the most commonly prescribed blood thinner; it blocks an enzyme called vitamin K epoxide reductase, resulting in lower levels of active vitamin K1 and a decrease in blood clotting ability. However, while warfarin is cheap and effective, the level of blood thinning achieved with warfarin is unpredictable, and therefore, constant monitoring and dose adjustment are required.
Recently, a new class of drugs called non-vitamin K antagonist oral anticoagulants (NOACs) has become available. Currently, four NOACs are approved for use. Of these, dabigatran is an inhibitor of thrombin, whereas rivaroxaban, edoxaban and apixaban are inhibitors of factor Xa. These drugs are indicated for the prevention of cardioembolic disease in non-valvular atrial fibrillation as well as the treatment and prevention of venous thromboembolism. Although these drugs are fast acting and do not require regular blood monitoring or dose adjustment, major questions about their efficacy and safety remain.
A new study, published in Clinical Therapeutics in June 2017, reviewed data from previous randomized control trials and observational studies to evaluate the efficacy and safety of NOACs compared to vitamin K antagonists.1The study collected data from research published between January 1, 2005, and February 15, 2016. The effectiveness of the drugs against atrial fibrillation was examined by checking if they reduced stroke and/or systemic embolism. Also, assessed was their ability to reduce recurrent venous thromboembolism or fatal pulmonary embolism. Additionally, the safety of these drugs was examined by evaluating major bleeding events during drug intake.
Occurrences of stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction (MI), and all-cause mortality were used to evaluate secondary effectiveness of the drugs against atrial fibrillation. Recurrent deep vein thrombosis, recurrent nonfatal pulmonary embolism, and all-cause mortality were used to assess secondary effectiveness against venous thromboembolism. The metrics for secondary safety of the drugs included intracranial hemorrhage and gastrointestinal bleeding.
The results showed that, overall, NOACs were superior or comparable to traditional vitamin K antagonists in terms of efficacy and safety. The risk for bleeding events, myocardial infarction, hemorrhagic stroke, all-cause mortality, and intracranial hemorrhage were different for the four NOACs. The paper also noted that major bleeding events, myocardial infarction, all-cause mortality, and gastrointestinal bleeding events for dabigatran were highly variable across multiple observational studies and suggests that pooling patient samples from diverse countries and data sources and different follow-up times could be two of several causes for this variability.
One limitation of the study was that non-English language publications were not included in the analysis.As a result, the recommendations may not be generalizable to populations that were not included. Another limitation was that for the NOACs apixaban and edoxaban, data from a lone randomized clinical trial were included, and no observational data were available.More research is urgently needed to assess the safety and efficacy of these drugs.
Finally, by rigorously analyzing the efficacy and safety of the NOAC drug class, this study fills a critical knowledge gap, which may help in evidence-based clinical decision-making and improve patient care.
Written by Usha B. Nair, Ph.D.
- Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, Lo-Ciganic WH. Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-Analyses. Clin Ther. 2017 Jun 28. pii: S0149-2918(17)30699-9. doi: 10.1016/j.clinthera.2017.05.358. [Epub ahead of print] Review. PubMed PMID: 28668628.