What is the clinical evidence from this study?

Study design: Review. Population: Atherosclerotic disease (CAD, PAD, ACS). Intervention: Dual pathway inhibition (rivaroxaban plus aspirin) vs. Aspirin alone or standard antiplatelet therapy.

June 28, 2020Open Access

Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence

Key Result

Dual pathway inhibition with rivaroxaban 2.5 mg twice daily plus aspirin significantly reduces the risk of atherothrombotic events compared with aspirin alone across a broad range of patients with atherosclerotic disease.

Structured PICO

Does dual pathway inhibition with rivaroxaban and aspirin reduce atherothrombotic events in patients with atherosclerotic disease?

Population

A review of clinical evidence for dual pathway inhibition in patients with atherosclerotic disease, including acute coronary syndrome, chronic coronary artery disease, and peripheral artery disease.

Intervention

Dual pathway inhibition (DPI) combining an anticoagulant (rivaroxaban 2.5 mg twice daily) with an antiplatelet agent (aspirin).

Comparator

Standard of care antiplatelet therapy (single antiplatelet therapy with aspirin alone, or dual antiplatelet therapy).

Outcome

Atherothrombotic events (composite of cardiovascular death, myocardial infarction, stroke, and major adverse limb events).composite

Dual pathway inhibition with low-dose rivaroxaban and aspirin provides superior vascular protection compared to aspirin alone for secondary prevention in patients with atherosclerotic disease, with a favorable benefit-risk profile.

Limitations

Increased risk of major bleeding with dual pathway inhibition compared to aspirin alone
Lack of head-to-head comparisons between dual antiplatelet therapy and dual pathway inhibition in patients with cardiovascular disease

Abstract

Despite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.

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