Bayer’s Xarelto (Rivaroxaban) meets primary efficacy endpoint, shows significant reduction in mortality in major study

Bayer HealthCare announced that the combination of oral Xarelto (Rivaroxaban) twice daily with standard antiplatelet therapy significantly reduced the composite primary efficacy endpoint of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome (ACS) compared to those receiving standard antiplatelet therapy alone.

In addition, rivaroxaban 2.5 mg in combination with standard therapy significantly reduced mortality over standard therapy alone. Results from the pivotal Phase III ATLAS ACS 2-TIMI 51 study presented at the American Heart Association Scientific Sessions and published by the New England Journal of Medicine also showed that rivaroxaban significantly increased the rate of major bleeding, but did not increase the risk of fatal bleeding over standard therapy alone.

ACS occurs when a blood clot blocks a coronary artery, which can lead to heart attacks or chest pain known as unstable angina.

"The clinical benefit of giving rivaroxaban in combination with standard antiplatelet therapy seen in the ATLAS ACS 2-TIMI 51 study is welcome, and could lead to significant improvement in the management of patients with acute coronary syndrome," said Eugene Braunwald, MD, Distinguished Hersey Professor of Medicine at Harvard Medical School and founding chairman of the Thrombolysis In Myocardial Infarction (TIMI) Study Group, Brigham and Women’s Hospital.

"For more than a decade ACS patients have been effectively treated with a low-dose aspirin given in combination with a thienopyridine to help reduce their risk of a recurrent cardiovascular event. This study showed that by adding the oral Factor Xa inhibitor rivaroxaban to standard therapy, this risk is greatly reduced, resulting in a significant reduction in mortality," said C Michael Gibson, MD, senior investigator of the TIMI Study Group, Harvard Medical School, and the principal investigator in the ATLAS ACS studies of rivaroxaban.

"If the data from ATLAS ACS 2-TIMI 51 were extrapolated into clinical practice, we could potentially see one life saved for every 56 patients treated with this combination of therapies over a two year period."

The results of the ATLAS ACS 2-TIMI 51 study showed that both 2.5 and 5 mg of rivaroxaban dosed twice daily (BID) in addition to standard therapy — low-dose aspirin with or without a thienopyridine such as clopidogrel — were superior to standard therapy plus placebo in both study arms in the primary efficacy endpoint of preventing recurrent major cardiovascular events (cardiovascular death, myocardial infarction and stroke) in patients with ACS [combined doses 8.9 percent vs. 10.7 percent (P=0.008), Relative Risk Reduction (RRR)=16 percent]. Additionally and importantly, rivaroxaban significantly reduced stent thrombosis compared with placebo [2.3 percent vs 2.9 percent (P=0.016)].

Patients dosed with 2.5 mg BID of rivaroxaban showed a significant reduction in risk of the composite primary endpoint [9.1 percent vs 10.7 percent (P=0.020)], driven by a significant 34 percent RRR in the rate of cardiovascular death [2.7 percent vs 4.1 percent (P=0.002)]. There was also a significant reduction in deaths from any cause [2.9 percent vs 4.5 percent (P=0.002)]. The 5 mg BID dose of rivaroxaban also significantly reduced the rate of the primary efficacy endpoint in the study [8.8 percent vs 10.7 percent (P=0.028)].

The principal safety endpoint for the study was TIMI major bleeding not associated with coronary artery bypass graft (CABG) surgery. In patients receiving rivaroxaban in combination with standard therapy, bleeding rates were statistically significantly increased versus those treated with standard therapy plus placebo [2.1 percent vs 0.6 percent (P<0.001)].

Similarly, rivaroxaban resulted in higher rates of TIMI major bleeding events not associated with CABG surgery at both the 2.5 mg and 5 mg BID doses compared to placebo [1.8 percent vs 0.6 percent (P<0.001) and 2.4 percent vs 0.6 percent (P<0.001), respectively]. Importantly, rivaroxaban did not increase the risk of fatal bleeding. Other treatment-emergent adverse events were generally balanced across treatment groups.

The US Food and Drug Administration (FDA) has granted rivaroxaban "fast track" designation for this indication, given the seriousness of ACS as a medical condition and the potential clinical benefit of rivaroxaban.

"These important results demonstrate that rivaroxaban can help patients with acute coronary syndrome," said Dr Kemal Malik, member of the Bayer HealthCare executive committee and chief medical officer. "Acute coronary syndrome is a chronic, life-threatening condition, and we believe, based on these data, that rivaroxaban could greatly improve the current standard of care."