LAUSR

BACKGROUND To evaluate the efficacy and safety of Xa inhibitors in patients with heart failure (HF) and coronary artery disease (CAD) or peripheral artery disease (PAD). METHODS A systematic electronic literature search was performed using the PubMed, Web of Science, EMBASE, and Cochrane Library databases from inception to June 26, 2019. A total of four randomized controlled trials involving 14,694 patients were included in this meta-analysis. RESULTS The meta-analysis showed that there was no statistical difference between the Xa inhibitor and control group regarding the primary efficacy outcome [rivaroxaban 2.5 mg group: relative risk (RR) 0.82, 95% CI: 0.66-1.01, P=0.06; rivaroxaban 5 mg group: RR 0.86, 95% CI: 0.73-1.02, P=0.08]. The risk of the primary safety outcome was significantly increased among patients who received Xa inhibitors compared with the control group (rivaroxaban 2.5 mg group: RR 1.55, 95% CI: 1.21-1.98, P=0.0006; rivaroxaban 5 mg group: RR 1.66, 95% CI: 1.30-2.12, P<0.0001). There was no significant difference in the risk of cardiovascular death between the Xa inhibitor and control group (rivaroxaban 2.5 mg group: RR 0.79, 95% CI: 0.54-1.14, P=0.21; rivaroxaban 5 mg group: RR 0.89, 95% CI: 0.73-1.08, P=0.24). The risk of myocardial infarction (MI) in the rivaroxaban 5 mg group was significantly lower than that of the control group (RR 0.83, 95% CI: 0.69-0.99, P=0.04). However, the risk of MI in the rivaroxaban 2.5 mg group was similar to that of the control group (RR 0.85, 95% CI: 0.71-1.01, P=0.07). DISCUSSION Xa inhibitors were associated with a higher risk of major adverse cardiovascular events and bleeding among HF and CAD or PAD patients. Therefore, Xa inhibitors should be used cautiously in patients with HF and CAD or PAD.