Patients with ACS who were treated with 2.5 mg rivaroxaban twice per day had a net reduction in irreversible or fatal events, according to a study published in the Journal of the American College of Cardiology.

The net clinical outcome of rivaroxaban (Xarelto, Janssen) was assessed through clinically significant events, particularly fatal or irreversible ischemia or bleeding, according to the study.

ATLAS ACS 2-TIMI 51 data

C. Michael Gibson, MS, MD, professor of medicine at Harvard Medical School and chief of clinical research at Beth Israel Deaconess Medical Center, and colleagues analyzed data of patients with ACS from the ATLAS ACS 2-TIMI 51 trial.

As Cardiology Today previously reported, the ATLAS ACS 2-TIMI 51 trial found that rivaroxaban, when added to standard treatment, reduced the risk for CV death, MI and stroke among patients with ACS, but was associated with an increase in TIMI major bleeding. This trial also found that giving 2.5 mg twice-daily rivaroxaban can reduce the rates of stent thrombosis and mortality among stented patients with ACS who are treated with dual antiplatelet therapy.

Compared with patients assigned placebo, those assigned 2.5 mg rivaroxaban twice per day had 115 (95% CI, 18-212) fewer irreversible or fatal ischemic events (663 vs. 548) per 10,000 patient-years of exposure. This also resulted in 10 (95% CI, –11 to 32) additional irreversible or fatal seriously harmful events per 10,000 patient-years of exposure (33 vs. 23).

Prevented events

Rivaroxaban was associated with 105 prevented irreversible or fatal events per 10,000 patient-years of exposure compared with the placebo group. There would also be 11 prevented irreversible or fatal ischemic events for each irreversible or fatal harmful event caused, according to the researchers.

Patients assigned 2.5 mg of rivaroxaban twice per day would have 95 prevented events per 10,000 patient-years of exposure if only nonbleeding CV death was included as an irreversible or fatal event, the researchers wrote.

“The present study used a methodology that separated events into those fatal or irreversible ischemic events that were prevented and compared them with the harmful fatal or irreversible events caused by a pharmacotherapy,” Gibson and colleagues wrote. “In this form of analysis, only fatal or irreversible events were included so that benefit and seriously harmful events of similar clinical impact were compared. This is particularly important when the endpoints and analyses do not include measurements of subjective clinical impact such as utility measurements or preference weights. This approach also uses risk differences rather than relative measurements such as hazard ratios, so the number of events prevented and caused are clearly distinguished.”

In a related editorial, Eugenia Nikolsky, MD, PhD, attending cardiologist and director of clinical research in invasive cardiology at Rambam Health Care Campus and Technion-Israel Institute of Technology in Haifa, and Freek W.A. Verheugt, MD, professor of cardiology at Heart-Lung Centre of the University Medical Centre in Nijmegen, the Netherlands, and chair of cardiology at Onze Lieve Vrouwe Gasthuis in Amsterdam, wrote: “Reduction of recurrent ischemic events without increase in bleeding complications continues to be the main target in the contemporary ACS trials of novel antiplatelet or antithrombotic regimens. Although we are getting closer to therapy optimization, the final word regarding the use of low-dose rivaroxaban and other agents for secondary prevention of cardiovascular diseases has not yet been said. This is primarily due to substantial variation in the magnitude of the risks and benefits across a population.” – by Darlene Dobkowski