Patients with nonvalvular atrial fibrillation who underwent PCI with stenting had a lower rate of clinically significant bleeding if they received treatment regimen that included rivaroxaban than if they received a standard regimen that included a vitamin K antagonist, according to a randomized trial.
Lead researcher C. Michael Gibson, MD, PhD, of Beth Israel Deaconness Medical Center and Harvard Medical School in Boston, presented the results in a late-breaking clinical trials session at the American Heart Association Scientific Sessions in New Orleans.
The findings were simultaneously published in the New England Journal of Medicine on Nov. 14. Janssen Scientific Affairs and Bayer Pharmaceuticals, which manufacture rivaroxaban, funded the study.
“In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,” Gibson said in a news release. “This trial, which tested two entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with anti-platelet therapy is successful in minimizing bleeding while preventing clotting.”
The FDA has approved rivaroxaban (Xarelto) to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The oral medication is also approved to treat deep vein thrombosis and pulmonary embolism and to reduce the risk of recurrent deep vein thrombosis and pulmonary embolism.
Patients with nonvalvular atrial fibrillation are instructed to take 15 mg or 20 mg once daily with their evening meal. Gibson said that an estimated 20 million people in the U.S. and Europe have atrial fibrillation. He added that 5 percent to 10 percent of patients who enter the cardiac catheterization laboratory have atrial fibrillation and need a stent.
“This is a substantial number of patients who present this kind of treatment dilemma,” Gibson said during a news conference.
Gibson mentioned that the best way to treat atrial fibrillation is to prescribe anticoagulation, while the best way to treat stenting is to prescribe dual antiplatelet therapy. Patients with both conditions typically receive a combination of anticoagulation and dual antiplatelet therapy, according to Gibson. However, he said that that strategy often leads to excess bleeding.
In this trial, known as PIONEER AF-PCI, the researchers randomly assigned 2,124 participants with nonvalvular atrial fibrillation who underwent PCI with stenting to one of three groups from May 2013 through July 2015.
The first group received 15 mg once daily of rivaroxaban and a P2Y12 inhibitor for 12 months, the second group received 2.5 mg of rivaroxaban twice daily plus dual antiplatelet therapy for one, six or 12 months and the third group received a dose-adjusted vitamin K antagonist once daily plus dual antiplatelet therapy for one, six or 12 months.
After 12 months of therapy, the rates of clinically significant bleeding were 16.8 percent, 18 percent and 26.7 percent, respectively. Gibbons said that physicians only need to treat 12 patients in the 2.5 mg rivaroxaban group to prevent one bleeding event and 11 patients in the 15 mg rivaroxaban group to prevent one bleeding event.
The researchers defined clinically significant bleeding as the composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction criteria or bleeding requiring medical attention. The results were consistent across several subgroups.
“It didn’t matter about kidney function, CHADS score, age, gender,” Gibson said. “The results all favored the rivaroxaban strategies.”
Meanwhile, the rates of death from cardiovascular causes, MI or stroke were 6.5 percent, 5.6 percent and 6 percent, respectively. The rates for each of the three components of the endpoint were similar between the groups. The rates of stent thrombosis were also similar.
The researchers also found that recurrent hospitalizations occurred in 31.2 percent of patients in the rivaroxaban plus dual antiplatelet therapy group, 34.2 percent of patients in the rivaroxaban plus P2Y12 inhibitor group and 41.5 percent of patients in the vitamin K antagonist plus dual antiplatelet therapy group.
Gibson said that physicians would have to treat 10 to 14 patients to prevent one recurrent hospitalization. Those results were presented at the conference and were simultaneously published online in Circulation on Nov. 14.
“This is, I think, very compelling data from a health economics perspective,” Gibson said.
The researchers acknowledged that the study had a few limitations, including that the trial was not powered to establish superiority or noninferiority with regards to efficacy. They also mentioned that the individual efficacy endpoints within subgroups were underpowered.
“As a result of all these limitations, it is inappropriate to draw firm conclusions regarding efficacy from these data,” the researchers wrote.