Efficacy and safety of adding rivaroxaban to the anti-platelet regimen in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Rivaroxaban, a direct factor Xa inhibitor, has seldom been used in patients with coronary artery disease. In this analysis, we aimed to systematically compare the efficacy and safety of rivaroxaban in addition to the anti-platelet regimen in patients with coronary artery disease.

METHODS: Online databases (MEDLINE, EMBASE, Cochrane database, www.ClinicalTrials.gov and Google scholar were searched for randomized controlled trials which were exclusively based on patients with coronary artery disease; and which compared efficacy (cardiovascular outcomes) and safety (bleeding outcomes) outcomes with the addition of rivaroxaban to the other anti-platelet agents. Analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) and 95% confidence intervals (CI) were generated following data input.

RESULTS: Four trials with a total number of 40,148 patients were included (23,231 participants were treated with rivaroxaban whereas 16,919 participants were treated with placebo) in this analysis. Patients' enrollment period varied from years 2006 to 2016. The current results showed addition of rivaroxaban to significantly lower composite endpoints (OR: 0.81, 95% CI: 0.74-0.88; P = 0.00001). In addition, all-cause death, cardiac death, myocardial infarction, and stent thrombosis were also significantly reduced (OR: 0.82, 95% CI: 0.72-0.92; P = 0.0009), (OR: 0.80, 95% CI: 0.69-0.92; P = 0.002), (OR: 0.87, 95% CI: 0.77-0.98; P = 0.03) and (OR: 0.73, 95% CI: 0.55-0.97; P = 0.03) respectively. However, stroke was not significantly different. However, TIMI defined minor and major bleeding were significantly higher with rivaroxaban (OR: 2.27, 95% CI: 1.47-3.49; P = 0.0002) and (OR: 3.44, 95% CI: 1.13-10.52; P = 0.03) respectively. In addition, intracranial hemorrhage and bleeding which was defined according to the International Society on Thrombosis and Hemostasis criteria were also significantly higher with rivaroxaban (OR: 1.63, 95% CI: 1.04-2.56; P = 0.03) and (OR: 1.80, 95% CI: 1.45-2.22; P = 0.00001) respectively. Nevertheless, fatal bleeding was not significantly different.

CONCLUSIONS: Addition of rivaroxaban to the anti-platelet regimen was effective in patients with coronary artery disease, but the safety outcomes were doubtful. Further future trials will be able to completely solve this issue.