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The 2.5-mg BID dosage resulted in a lower prevalence of fatal bleeding compared with the 5-mg BID dosage (0.1% vs 0.4%; P = 0.04), but this prevalence was not statistically different compared with placebo (0.1% vs 0.2%). 38 The European Society of Cardiology (ESC) Working Group Position Paper recommends the use of newer antiplatelet agents (ie, prasugrel or ticagrelor) in combination with aspirin over the addition of a factor Xa inhibitor in patients with ACS. This recommendation was a result of the increase in major and intracranial bleeding events when factor Xa inhibitors were combined with antiplatelet agents in clinical trials.47 Rivaroxaban is not currently approved for the treatment of ACS in any country. When comparing an agent to warfarin it is important to consider the percentage of time patients' [http://en.wikipedia.org/wiki/Oxygenase Oxygenase] international normalized ratios (INRs) were within [http://www.selleckchem.com/products/nu7441.html NU7441 datasheet] therapeutic range (TTR) in the warfarin-treated group because lower TTRs ([http://www.selleckchem.com/products/BKM-120.html BKM120 nmr] Connolly et al50 estimated that a TTR of 58% is needed to ensure that patients would benefit from VKA therapy. A criticism of ROCKET-AF findings is that the TTR was 55%, which is below this 58% threshold. However, ROCKET-AF investigators found that rivaroxaban efficacy was favorable across participating centers, regardless of the level of INR control attained at the center, meaning that rivaroxaban efficacy was similar in centers with the best and worst TTRs. Again, it is important to note that although this TTR is below that observed in contemporary clinical trials and dedicated anticoagulation clinics, it is better than those observed in community practice.48?and?49 Rivaroxaban, unlike VKAs, does not require routine coagulation monitoring. Although routine coagulation monitoring is unnecessary, there may be clinical situations in which the measurement of blood levels of rivaroxaban would be useful. Samama et al51?and?52 demonstrated the potential for using anti-factor Xa chromogenic and PT assays as a means to quantify plasma rivaroxaban levels. However, another group of investigators observed better correlation between anti-factor Xa activity and apixaban plasma concentrations.53 The data on this topic continue to emerge.