Discussion
bleeding
EVENTS, BLEEDING
The main finding of this equivalence and noninferiority feasibility trial is that rivaroxaban 5 mg twice daily in addition to DAPT in the acute phase of ACS for patients who missed the primary reperfusion window or before selective revascularization therapy was noninferior to enoxaparin in terms of bleeding risk and efficacy during the 6-month follow-up period. This finding provides useful information for designing future definitive RCTs with sufficient sample sizes to verify this clinical question. To our knowledge, this is the first clinical equivalence and noninferiority study describing the potential safety and efficacy of short-term low-dose rivaroxaban use in the acute phase of ACS.The noninferior margin we set is clinically accepted based on results of previous studies and FDA guidelines. The actual incidence of efficacy and safety end points may be used for calculating the sample size for future definitive RCTs.For patients with ACS missing the primary reperfusion therapy window, anticoagulation is effective in reducing ischemic events with background DAPT.Rivaroxaban exerts independent antiplatelet effects in addition to potent anticoagulant effects.Our objective was to explore whether rivaroxaban can be a substitute for enoxaparin during the acute phase of ACS. Therefore, rivaroxaban was not continued after the study period. The GEMINI-ACS-1 trialAs a feasibility trial with an insufficient sample size, our study supplied some useful information for designing future large-scale RCTs to verify our results, especially the appropriate noninferior margin for the primary end point of future definitive RCTs and the potential safety and that the efficacy of low-dose of rivaroxaban in patients hospitalized with ACS was clinically acceptable.Rivaroxaban has the advantages of being an oral therapy and fixed dose for all patients. Thus, rivaroxaban may be a good choice for prehospital management and may improve medication adherence. Our findings may help clinicians and patients with ACS in the acute phase choose the optimal anticoagulant therapy during the decision-making process.Although rivaroxaban at a dose of 2.5 mg did not show statistical noninferiority to enoxaparin in terms of the efficacy outcome, the MACE rate at the 6 months was similarly low in rivaroxaban 2.5 mg and enoxaparin groups. Therefore, patients with ACS may still have a chance to choose either a 2.5 or 5 mg twice daily dose plan according to their individual bleeding risk. Future regular noninferiority trials with larger sample sizes would fully address this gap.