Rivaroxaban in the contemporary treatment of acute coronary syndromes.

INTRODUCTION: Rivaroxaban is the first orally bioavailable direct factor Xa inhibitor and its role in acute coronary syndrome is not fully understood. A significant residual risk of recurrent ischemia remains in patients with acute coronary syndrome despite optimal medical therapy. Warfarin has demonstrated modest benefit that is offset by the risk of bleeding and complexity in its management. Rivaroxaban may be an attractive agent for the treatment of acute coronary syndromes given its predictable pharmacodynamics and favorable safety profile. AREAS COVERED: The current guideline-based antithrombotic and adjunctive medical therapies in acute coronary syndrome are summarized in this review. Rivaroxaban's drug profile, its current applications, ongoing trials and experience in patients with acute coronary syndrome are also described. EXPERT OPINION: Current experience of rivaroxaban in acute coronary syndrome demonstrates its safety and a trend towards benefit when added to current optimal medical therapy. The benefits were observed primarily in patients receiving aspirin monotherapy and increased bleeding among those receiving dual anti-platelet therapy. This suggests that there may be a narrow window between the optimal clinically achievable antithrombotic effect and the point where bleeding risk outweighs the benefits. Though promising, it remains to be seen if this drug will achieve the right balance between efficacy and bleeding risk.

Patterns of upstream antiplatelet therapy use before primary percutaneous coronary intervention for acute ST-elevation myocardial infarction (from the CRUSADE National Quality Improvement Initiative).

We sought to determine the usage patterns and impact of upstream glycoprotein IIb/IIIa inhibitor and clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We studied trends in the use of upstream glycoprotein IIb/IIIa inhibitors and clopidogrel in 3,895 patients with STEMI undergoing primary PCI at 124 hospitals in the United States participating in the CRUSADE initiative from March 2005 to December 2006. Administration of these agents >15 minutes before PCI was considered pre-PCI use, and administration < or =15 minutes before, during, and after PCI was considered peri-PCI use. A total of 3,566 patients (91.6%) received glycoprotein IIb/IIIa inhibitors within 24 hours of presentation, of whom 1,225 (34.4%) received this medication before PCI. Similarly, 3,785 patients (97.2%) received clopidogrel within 24 hours of presentation, of whom 1,029 (27.2%) received this medication before PCI. From 2005 to 2006, pre-PCI glycoprotein IIb/IIIa inhibitor use decreased from 43.4% to 33.5%, whereas pre-PCI clopidogrel use increased from 21.2% to 31.5%. Clinical characteristics, risk of adverse outcomes, and bleeding events were similar in the pre- versus peri-PCI glycoprotein IIb/IIIa inhibitor and clopidogrel cohorts, respectively. In conclusion, most patients with STEMI undergoing primary PCI receive glycoprotein IIb/IIIa inhibitors and clopidogrel, but only (1/3) are treated upstream with these agents and this upstream use does not have a significant impact on outcomes. These results indicate that further studies are needed to determine the optimal dosing and timing of antiplatelet therapies for patients undergoing primary PCI.

Use of and inhospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE).

BACKGROUND: Although current guidelines recommend early initiation of clopidogrel in patients with non-ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early (<24 hours of arrival) clopidogrel use and its association with clinical outcomes in patients with NSTEMI not undergoing early percutaneous intervention (PCI). METHODS: Using data from the CRUSADE initiative, after the exclusion of patients who underwent PCI within 24 hours of arrival, we studied trends in early clopidogrel use among 93,045 patients with NSTEMI. Multivariable logistic regression models were used to determine the association between early clopidogrel treatment and inhospital outcomes. RESULTS: A total of 38.6% of the NSTEMI patients not undergoing PCI within 24 hours of arrival received early clopidogrel. Adjusted inhospital mortality rate was lower in the early clopidogrel group compared to the group that did not receive it on admission (odds ratio 0.68, 95% CI 0.61-0.77). The rate of major bleeding in patients not undergoing coronary artery bypass surgery was similar among the groups treated with and without early clopidogrel (9.5% vs 9.5%, P = .90). CONCLUSIONS: Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding.