Do Direct Oral Anticoagulants (DOACs) prevent Atherosclerotic Cardiovascular Disease (ASCVD) events of atherosclerotic origin?

From the Guidelines

Direct oral anticoagulants (DOACs) do not prevent atherosclerotic cardiovascular disease (ASCVD) events. DOACs, which include medications like apixaban, rivaroxaban, dabigatran, and edoxaban, work by inhibiting specific clotting factors in the coagulation cascade, primarily targeting thrombin or factor Xa. While these medications are effective for preventing and treating conditions related to pathological blood clot formation such as atrial fibrillation-related stroke, venous thromboembolism, and pulmonary embolism, they do not address the underlying process of atherosclerosis. Atherosclerosis involves the buildup of cholesterol plaques in arterial walls through inflammatory processes and lipid accumulation, which DOACs do not influence.

For prevention of atherosclerotic events, medications that target the atherosclerotic process itself are needed, such as statins to lower cholesterol, antihypertensives to control blood pressure, antiplatelet agents like aspirin or P2Y12 inhibitors, and lifestyle modifications including diet changes, exercise, and smoking cessation. These interventions address the fundamental pathophysiology of atherosclerosis by reducing plaque formation or progression, while DOACs only prevent clot formation after a plaque has ruptured. According to the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1, the role of DOACs in secondary stroke prevention for patients with recent noncardioembolic stroke remains an unanswered question, highlighting the need for further research in this area.

The 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease 1 emphasizes the importance of promoting a healthy lifestyle throughout life to prevent ASCVD, including improvements in diet, physical activity, and avoidance of tobacco use and exposure to secondhand smoke. The 2024 ESC guidelines for the management of atrial fibrillation 1 also recommend oral anticoagulation in patients with clinical AF at elevated thromboembolic risk to prevent ischemic stroke and thromboembolism, but do not address the prevention of atherosclerotic events.

Key points to consider:

• DOACs do not prevent atherosclerotic events
• Atherosclerosis involves the buildup of cholesterol plaques in arterial walls
• Medications that target the atherosclerotic process itself are needed to prevent atherosclerotic events
• Lifestyle modifications, including diet changes, exercise, and smoking cessation, are essential for preventing atherosclerotic events.

From the Research

DOACs and Atherosclerotic Origin of ASCVD Events

• The use of Direct Oral Anticoagulants (DOACs) in preventing atherosclerotic origin of Atherosclerotic Cardiovascular Disease (ASCVD) events is a topic of interest in current medical research 2.
• DOACs have been found to exert pleiotropic effects on atherosclerotic progression through coagulation and inflammatory pathways, which may help in preventing ASCVD events 2.
• However, the balance between efficacy and harm remains a challenge in the adoption of DOACs for secondary atherosclerotic disease prevention 2.
• Studies have shown that low-dose DOACs may be effective in select stable Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD) patients, but careful individual considerations must be undertaken 2.
• The use of DOACs in patients with Atrial Fibrillation (AF) undergoing Percutaneous Coronary Interventions (PCI) is also being explored, with evidence favoring the use of dual therapy with DOAC due to prohibitory bleeding with triple anti-thrombotic therapy 2.

Mechanism of Action

• DOACs work by inhibiting specific clotting factors, thereby preventing the formation of thrombi or the propagation of an existing clot 3.
• The mechanism of action of DOACs is different from that of traditional anticoagulants, such as vitamin K antagonists, and may offer advantages in terms of efficacy and safety 4.

Clinical Use

• DOACs are indicated for the prevention and treatment of several cardiovascular conditions, including stroke prevention in AF and the management of venous thromboembolism 5, 6.
• The choice of DOAC and the duration of treatment depend on various factors, including the patient's underlying condition, comorbidities, and risk of bleeding 5, 6.