DOAC or VKA?

Illnesses that necessitate anticoagulation

About 1% of the general population (350,000 Canadians) is on anticoagulation treatment, and that number is growing by over 10% each year. About 6% of the population over 65 years of age lives with atrial fibrillation (AF), a condition that requires oral anticoagulation to prevent strokes and other serious blood clotting problems.

In addition to AF, anticoagulants are often prescribed to people who have artificial heart valves or who have had a heart attack or other heart diseases that increase the risk of developing blood clots.

DOAC or VKA? Criteria for choosing the right treatment

For long-term oral anticoagulation, medications from the vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) groups are available.

Unlike with VKAs, the mode of action of DOACs does not need to be monitored. However, while this is often regarded as an advantage, it has come under criticism from an increasing number of healthcare professionals because, especially with non-compliant patients, the absence of a control parameter can become a challenge for the dosage adjustment.

Considerations for choosing an anticoagulant regimen:

The following patient-related factors are important when deciding between a VKA and a DOAC:

• Risk of bleeding^1,2
• HAS-BLED score (≥ 3 points = high risk)¹
• A mechanical heart valve or hemodynamically significant valve disease²
• Renal function^2,3
• Advanced liver disease²
• Body weight³
• Risk of coronary events³
• Propensity to dyspepsia³
• Patient compliance and preferences¹
• Ability to safely sustain adjusted chronic anticoagulation¹
• Success on existing anticoagulation therapy²

For patients in the following subgroups, VKAs (such as warfarin) plus monitoring remain the standard of care where:

• There is a risk of non-compliance^4–6
• There are comorbidities (hypertension, heart failure, diabetes)⁶
• The patient has renal impairment⁵
• The patient has a mechanical heart valve⁶
• The patient is elderly (> 75 years)⁶
• The patient has an increased risk of bleeding⁷
• Cost is an issue⁷
• The patient is a child or adolescent⁷
• The patient is intolerant to the new drugs⁸

Studies involving non-valvular atrial fibrillation indicate that DOACs are at least equivalent to VKAs. Although heavy, especially intracranial, bleeding is reported less frequently than with VKAs, a closer analysis revealed that with correct international normalized ratio (INR) adjustment, these advantages during the thrombosis prophylaxis disappear with VKAs.⁹ Furthermore, an increased risk of gastrointestinal bleeding has been shown with DOACs.¹⁰

When using VKA therapy, the right dose adjustments may be more easily attained when the INR checks are done in the form of patient self-testing.¹¹

References:

1. Camm AJ et al. Eur Heart J. 2010;31(19):2369–2429.
2. Fuster V et al. Circulation. 2011;123:e269–e367.
3. Cairns JA et al. Can J Cardiol. 2011;27(1):74–90.
4. United Kingdom Clinical Pharmacy Association Position Statement on Introduction of the New Oral Anticoagulant.
5. Wann LS et al. J Am Coll Cardiol. 2011;57(11):1330–1337.
6. Fuster V et al. Circulation. 2011;123(10):269–367.
7. Market research with 288 GPs and 29 experts from Australia, Germany, UK, USA; Q2 2011.
8. Connolly SJ et al. N Engl J Med. 2009;361:1139–1151.
9. Wallentin L et al. Lancet. 2010;376(9745):975–983.
10. Connolly SJ et al. NEJM. 2009;361:1139–1151.
11. Heneghan C et al. Lancet. 2012;379(9813):322–334.

The importance of Coumadin derivatives

Anticoagulation with vitamin K antagonists (VKAs) is a long-established and proven treatment option. Moreover, there is a wealth of experience in the use of VKAs.

Patients receiving VKA therapy have very stable coagulation values, especially if they control the monitoring as coagulation self-testers and adjust their anticoagulant dosage themselves. As far back as 2001, a major study revealed that self-managers were able to maintain 80% of their measured levels within the therapeutic range.¹ In contrast, this percentage was only 65% in patients who received conventional care. The reasons for the difference were weekly monitoring and the ability to react quickly to INR deviations from the therapeutic range by an immediate dosage adjustment.

References:

1. Kortke H et al. Ann Thorac Surg. 2001;72(1):44–48.

Direct oral anticoagulants on the market

In the last few years, several new drugs have been cleared for anticoagulation use. These direct oral anticoagulants (DOACs, formerly referred to as NOACs) offer the following benefits:^1,2

• Do not require monitoring
• Wider therapeutic index
• Simpler kinetics
• More rapid onset/offset
• Fewer or absent drug and food interactions

DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban demonstrated non-inferiority with warfarin in prevention of stroke and systemic embolism. Secondary analyses demonstrated superiority for apixaban and dabigatran, 150 mg dose.

In each of these studies, the warfarin group was monitored using the usual care model. Warfarin patients who self-monitored once per week or every other week experienced dramatic increases in time in therapeutic range (TTR) with decreases in adverse events compared to patients managed under usual care.

NOAC: non-vitamin K oral anticoagulant

References:

1. Kearon C et al. Chest. 2008;133(6 Suppl):454S–545S.
2. Singer DE et al. Chest. 2008;133(6 Suppl):546S–592S.