Combining rivaroxaban with aspirin for peripheral artery disease: an in-depth systematic review and meta-analysis

Abstract

Funding Acknowledgements None. Introduction Peripheral artery disease (PAD) poses a significant challenge in the realm of cardiovascular medicine, necessitating a multifaceted approach to mitigate its impact and enhance patient outcomes. One treatment approach involves the combined use of rivaroxaban, a direct oral anticoagulant, and aspirin, a commonly used antiplatelet agent in decreasing possible complications that can develop in patients with PAD. Methods An extensive search of randomized controlled trials (RCTs) comparing the efficacy of rivaroxaban in combination with aspirin versus aspirin monotherapy among individuals diagnosed with peripheral artery disease. The assessment of this treatment approach involved evaluating the following primary outcomes: a decrease in major adverse cardiovascular events (MACE) and the need for major amputation. Safety profile was also evaluated by examining the rate of major bleeding, utilizing the scoring tool from International Society of Thrombosis and Hemostasis (ISTH). The analyses were performed using a random effects analysis approach via Review Manager V5.4. Results This meta-analysis encompassed three studies involving a total of 9,352 participants. There was reduction of MACE in rivaroxaban with aspirin therapy (RR 0.83 [95% CI: 0.71-0.97] I2 = 29%, p = 0.02] but there was no significant difference in terms of major amputation rates (RR 0.96 [95% CI: 0.80-1.14] I2 = 0%, p = 0.62). However, there was increased risk of bleeding in rivaroxaban with aspirin therapy (RR 1.46 [95% CI: 1.17-1.82] I2=0, p = 0.0009) compared to aspirin alone. Conclusion Rivaroxaban combined with aspirin therapy demonstrated a 17% reduction in MACE compared with aspirin monotherapy but didn’t reduce major amputation rates. Also, doing this strategy poses a higher risk of bleeding. Therefore, a balance between the risks and benefits of this combined therapy necessitates a thorough assessment of individual patient profiles, considering factors such as overall cardiovascular risk, comorbidities, and bleeding tendencies. Further research and long-term studies are needed to establish comprehensive guidelines for the appropriate utilization of this combination therapy in various patient populations.