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Major cardiovascular (CV) events often complicate the natural history of apparently stable atherothrombotic cardiovascular disease (CVD) despite appropriate guideline-based preventive treatment. This finding has been termed residual risk and it has been the focus of recent investigation. New and revisited targets to tackle this so-called residual risk have been proposed, including antithrombotic treatment intensification, further lowering targets of low-density lipoprotein (LDL) cholesterol, novel oral antidiabetic agents with a CV benefit, and drugs to reduce systemic inflammation. In this narrative review, we discuss the evidence, mechanisms and gaps in knowledge concerning the vascular protection derived from low-dose (2.5 mg twice daily) rivaroxaban. On this topic, the main trials (ATLAS ACS 2-TIMI 51, COMPASS and VOYAGER PAD), will be summarized in a comprehensive manner. Indeed, these have shown that a drug developed to prevent thrombus formation (selective Factor Xa inhibition) reduced events that were traditionally platelet-related in concept. Moreover, we propose a simple evidence-based clinically oriented algorithm to thoroughly identify patients at increased risk and who may benefit from this strategy in different clinical scenarios. Low-dose rivaroxaban portrays a novel promising era in atherothrombotic CVD prevention, providing a mechanistic protection beyond traditional strategies in patients overwhelmed by recurrent dismal events.

A narrative review of low-dose rivaroxaban in patients with atherothrombotic cardiovascular disease: vascular protection beyond anticoagulation