Abstract 11382: The Efficacy and Safety of Low-Dose Rivaroxaban With or Without a Proton Pump Inhibitor: Insights From the ATLAS ACS 2-TIMI 51 Trial
Background: Omeprazole and esomeprazole can attenuate the pharmacodynamic effects of clopidogrel, although the clinical implications remain unclear. In ATLAS ACS 2-TIMI 52, rivaroxaban (RIVA) reduced the risk of CV events in patients after ACS regardless of background use of clopidogrel. Whether the efficacy of RIVA for patients on clopidogrel is impacted by the use of a proton pump inhibitor (PPI) is unknown.
Methods: ATLAS ACS 2-TIMI 51 enrolled 15,526 subjects and randomized them to RIVA 2.5mg PO BID, 5mg PO BID, or placebo on a background of aspirin. Mean treatment duration was 13 months. Randomization was stratified by intent to use a thienopyridine. The current analysis was restricted to stratum 2 (planned treatment with thienopyridine) and analyzed in the intention-to-treat population. Subjects were considered to be on a PPI if they reported use of omeprazole or esomeprazole at the baseline visit.
Results: In stratum 2, there were 2203 (15.2%) subjects who were recorded as receiving omeprazole or esomeprazole at randomization. RIVA (pooled) reduced the risk of CV death, MI or stroke in subjects who were or were not on a PPI at baseline [HR 0.68 (95% CI 0.50-0.93); HR 0.86 (95% CI 0.75-0.99), respectively; P for interaction=0.18). Consistent results were observed for RIVA to reduce the risk of CV death, MI or stroke at 30 days for subjects who were (HR 0.94, 95% CI 0.51-1.76) or were not (HR 0.69, 95% CI 0.51-0.91, P for interaction=0.37) on a PPI at randomization. For patients not on a PPI and on a thienopyridine, RIVA 2.5mg BID reduced the risk of CV death (HR 0.68, 95% CI 0.52-0.90) and all-cause death (HR 0.67, 95% CI 0.52-0.87) through long-term follow-up. There was no heterogeneity for patients who were or were not on a PPI in regards to the risk of long-term bleeding events on RIVA. Regardless of randomized treatment arm, the use of a PPI was not associated with an increased risk of CV events for patients on a thienopyridine (HR 1.01, 95% CI 0.84-1.21).
Conclusion: In ATLAS ACS 2-TIMI 52, RIVA reduced the risk of long-term CV events for subjects on a thienopyridine regardless of background PPI use. As well, use of a PPI did not appear to attenuate the clinical efficacy of clopidogrel.
- © 2013 by American Heart Association, Inc.