Table of Contents
Introduction
Thromboembolic diseases are often fatal; they are of major clinical concern as they have high prevalence rates and severe consequences. Following coronary diseases and stroke, venous thromboembolism (VTE) is estimated to be the third most common cardiovascular disorder. Therefore, treating venous and arterial thrombotic diseases is a major medical challenge. Hence the development of anticoagulant drugs is a revolution in medicine. Anticoagulant drugs can be given through the oral route or parenteral route.
For the last 60 years, the only oral anticoagulants used were vitamin K antagonists, which included coumarin derivatives like Warfarin and Acenocoumarol. However, a more predictable anticoagulant response was seen through novel oral anticoagulants (NOACs). NOACs are very effective in preventing stroke, treating venous thromboembolism, and preventing systemic embolism in patients with non-valvular atrial fibrillation. The dose for vitamin K antagonists is dependent on the individual basis, whereas NOACs are administered in fixed doses, except for patients with liver or kidney disorders. NOACs are also known as direct oral anticoagulants or target anticoagulants because they directly activate thrombin and factor X.
What Are Vitamin K Anticoagulants (VKA)?
Karl Paul Link, in 1941, discovered Dicoumarol and established oral anticoagulation. The anticoagulant action of the VKA medication, a derivative of 4-hydroxycoumarin, is caused by the inhibition of vitamin K epoxide reductase. VKA are used for various medical situations like:
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The treatment of deep vein thrombosis (DVT).
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Pulmonary embolism (PE).
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Prevention of recurrence.
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Atrial fibrillation (AF) and stroke in patients with NVAF (non-valvular atrial fibrillation).
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Acute myocardial infarction.
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Vasculopathy.
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In patients with tissue heart valves or mechanical prosthetic cardiac valves.
What Are Novel Oral Anticoagulants (NOACs)?
Newer oral anticoagulants are target anticoagulants which are direct-acting medications. They are selective for a specific coagulant factor, either thrombin or activated factor Xa. NOACs have been approved to prevent VTE patients after elective hip and knee arthroplasty.
Some examples of NOACs are:
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Dabigatran.
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Rivaroxaban.
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Apixaban.
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Edoxaban.
Dabigatran:
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Dabigatran was first approved by the European Medicine Agency in 2008 and Food and Drug Administration in 2010, based on a randomized evaluation of long-term anticoagulant therapy (RE-LY) trial for Warfarin, which was compared to Dabigatran. As a direct thrombin inhibitor, Dabigatran reduces the development of clots by preventing the conversion of fibrinogen to fibrin.
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This drug reduces the risk of stroke and systemic embolism in patients with non-vascular atrial fibrillation.
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Pradaxa is the trade name of Dabigatran.
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This drug is rapidly absorbed and can be administered with or without food. Enterocytes, hepatocytes, and portal veins are the areas where absorption and bioconversion of Dabigatran occur.
Rivaroxaban:
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Rivaroxaban is the second newer oral anticoagulant approved.
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Rivaroxabane is a selective FXa inhibitor. One dose of Rivaroxaban is sufficient to provide anticoagulant activity since the concentration of Rivaroxaban in 24 hours is 10 nanograms/milliliter, and its anti-factor Xa activity is 0.17 IU/milliliter.
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The usage of Rivaroxaban in senior people is not well documented, however, it is assumed that patients over 75 utilize a five-milligram dosage of the medication twice a day.
Apixaban:
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It is a reversible direct antagonist. It is similar to Rivaroxaban. The FDA and European Medicine Agency approved Apixaban as the third NOAC.
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Eliquis is the trade name of Apixaban.
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When it comes to preventing stroke and systemic embolism in AF patients, Apixaban is seen to be superior to Warfarin.
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The hemorrhagic stroke rate of 0.24 % per year was found in the Apixaban group compared to 0.47 % per year in the Warfarin group. Hence lower mortality rate was found in the Apixaban group than in the Warfarin group.
Edoxaban:
Edoxaban is an oral direct, specific inhibitor of FXa with approximately 10,000-fold selectivity for FXa over thrombin. In addition, the drug has a dual mechanism of elimination. According to the authors, Edoxaban proved to be a cost-effective alternative to Warfarin in these products.
What Are the Clinical Indications of NOACs?
Thromboembolic indications of NOACs are:
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Prevention of stroke.
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Systemic embolism in adults with non-valvular atrial fibrillation (NVAF).
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Treatment and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE).
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It is used as an adjunct to Aspirin therapy in the prevention of further cardiac events.
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Patients with peripheral artery disease (PAD).
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Prevention of atherothrombosis events in patients with acute coronary syndrome.
What Are the Contraindications of NAOCs?
NOACs are contraindicated in:
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Clinically significant active bleeding.
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Conditions associated with major bleeding.
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Hepatic diseases with coagulopathy.
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Uncontrolled hypertension.
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Severe liver disease.
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Recent surgery.
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Procedures involving the nervous system.
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Contraindicated in severe active bleeding cases.
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Dabigatran is contraindicated in severe renal impairment.
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Edoxaban and Rivaroxaban are contraindicated in patients with chronic cirrhosis liver cases.
What Are the Advantages of NOACs?
Advantageous in the prevention and treatment of patients with:
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Atrial Fibrillation.
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Pulmonary embolism.
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DVT.
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Stroke.
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Conditions related to inherited or acquired thrombophilia.
NOACs have rapid onset and offset of action, fewer drug interactions, and there is no need for the regular monitoring of coagulation. NOACs, compared with VKAs, are related to cost and the importance of compliance. There are short half-life NOACs. The advantages of short half-life NOACs are indicated in emergency surgery and bleeding cases due to the accumulation of drugs in the bloodstream. In case of traumatic injury and spontaneous bleeding, the lack of a specific antidote is a problem; hence urgent surgical intervention may be required.
Conclusion:
Vitamin K anticoagulants presented difficulties related to major food and drug interactions, such as great individual variability and the need for continuous monitoring, so additional coagulant drugs were developed. NOACs have been introduced in the past seven years. NOACs have various advantages over vitamin K anticoagulants, like preventing strokes in AF and NVAF. The major bleeding incidence is decreased, convenience to use, rapid onset and offset of action, short half-life, and lack of need for laboratory monitoring. NOACs should not be used in hepatic and renal diseases, in patients younger than 18 years of age, or in patients with mechanical heart valves. Some disadvantages of NOACs are higher cost, absence of a specific antidote, and limited drug experience. Future investigations will further elucidate the role of NOACs in thromboembolic disease prevention and treatment.
