The challenges and limitations of widespread direct oral anticoagulant treatment: practical suggestions for their best use

ABSTRACT

For many decades vitamin K antagonists (VKA), whilst extremely effective but associated with significant drawbacks, were the only drugs available for chronic anticoagulation. However, recently, novel direct oral anticoagulant drugs, completely different to VKA and at least as effective and safe as VKA, have been introduced in clinical practice and their use is becoming increasingly more widespread. Their availability can extend effective anticoagulant treatment to a larger number of subjects requiring anticoagulation and substantially improve the quality of life of many patients. However, these drugs and their use also have limitations. The aim of this article is to analyze these limitations and the challenges potentially associated with their use, a move crucial to promote proper, effective and safe use of the drugs in everyday practice.

KEYWORDS:

• Dabigatran
• rivaroxaban
• apixaban
• edoxaban
• direct anticoagulants
• anticoagulation
• limitations

Key issues

• After 60 years of vitamin K antagonist (VKA) use, new direct oral anticoagulant drugs (DOACs), completely different to VKA, are available for clinical use.

• DOACs are different drugs, with important differences in how they work and how they behave pharmacologically.

• Very large phase III clinical studies investigated the effects of four DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in patients with nonvalvular atrial fibrillation or venous thromboembolism, concluding that DOACs were at least as effective and safe as warfarin, and in some cases, even more effective and safer.

• DOACs should be prescribed in specific clinical conditions that need to be respected, with absolute contraindications in some cases and clinical conditions where particular caution is necessary.

• Some special populations (very elderly, very low body weight, impaired renal function, co-medication with P-glycoprotein or CYP3A4 inhibitors, high risk of bleeding) require particular attention.

• Specific antidotes are still not available for current clinical use, and management of patients with major bleeding or thrombotic complications, or who need emergency procedures, has not yet been standardized.

• Adherence to treatment is an important issue for effective DOAC use and is linked to the need for education, information, and patient follow-up.

• Specifically designed postmarketing, independent, long-term studies to investigate DOAC effectiveness and safety in real-life settings are absolutely necessary.