Rivaroxaban Plus Aspirin versus Clopidogrel Plus Aspirin after Infrainguinal Endovascular Revascularization: A Narrative Review

Abstract

The conceptual framework of targeting the coagulation cascade in Peripheral Artery Disease (PAD) is not novel; however, early attempts were marred by unacceptable safety profiles. The introduction of Rivaroxaban represented a profound pharmacological paradigm shift. Unlike Warfarin, which broadly and somewhat unpredictably inhibits the synthesis of multiple vitamin K-dependent clotting factors (Factors II, VII, IX, and X), Rivaroxaban is highly targeted and possesses predictable pharmacokinetics. The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) was the seminal study that resurrected the "Dual Pathway" theory, proving it could be executed safely and effectively in clinical practice. The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) was specifically designed to determine if DPI could improve outcomes during this acute post-procedural phase. Because VOYAGER PAD compared Rivaroxaban + Aspirin to Aspirin monotherapy (with or without background clopidogrel), a "pure," large-scale randomized control trial specifically comparing Rivaroxaban + Aspirin (DPI) head-to-head against the clinical standard of Clopidogrel + Aspirin (DAPT) is lacking.