Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy

Abstract

Background: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y₁₂ inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization.

Methods: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y₁₂ inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment.

Results: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62-0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not.

Conclusions: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y₁₂ inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Keywords: atrial fibrillation; percutaneous coronary intervention; rivaroxaban; vitamin K.

Figure 1.

Time to all-cause death or first recurrent hospitalization. The treatment-emergent period is the period starting after the first study drug administration following randomization and ending 2 days after the study drug was stopped. Hazard ratios (HRs) compared with the vitamin K antagonist (VKA) group are based on the Cox proportional hazards model. Rehospitalizations do not include first index event hospitalization. Log-rank P values compared with the VKA group are based on the 2-sided log-rank test. ARR indicates absolute risk reduction; NNT, number needed to treat; Riva+DAPT, rivaroxaban 2.4 mg twice daily plus background dual antiplatelet therapy with low-dose aspirin; and Riva+P2Y₁₂, rivaroxaban 15 mg once daily+P2Y₁₂ inhibitor.

Figure 2.

Time to first recurrent hospitalization. The treatment-emergent period is the period starting after the first study drug administration following randomization and ending 2 days after the study drug was stopped. Hazard ratios (HRs) compared with the vitamin K antagonist (VKA) group are based on the Cox proportional hazards model. Rehospitalizations do not include first index event hospitalization. Log-rank P values compared with VKA group are based on the 2-sided log-rank test. ARR indicates absolute risk reduction; NNT, number needed to treat; Riva+DAPT, rivaroxaban 2.4 mg twice daily plus background dual antiplatelet therapy with low-dose aspirin; and Riva+P2Y₁₂, rivaroxaban 15 mg once daily+P2Y₁₂ inhibitor.

Figure 3.

Time to first recurrent hospitalization caused by cardiovascular or bleeding event. The treatment-emergent period is the period starting after the first study drug administration following randomization and ending 2 days after the study drug was stopped. Hazard ratios (HRs) compared with the vitamin K antagonist (VKA) group are based on the Cox proportional hazards model. Rehospitalizations do not include first index event hospitalization. Log-rank P values compared with the VKA group are based on the 2-sided log-rank test. ARR indicates absolute risk reduction; NNT, number needed to treat; Riva+DAPT, rivaroxaban 2.4 mg twice daily plus background dual antiplatelet therapy with low-dose aspirin; and Riva+P2Y₁₂, rivaroxaban 15 mg once daily+P2Y₁₂ inhibitor.

Figure 4.

Time to first recurrent hospitalization caused by combined bleeding or cardiovascular event or other event. The treatment-emergent period is the period starting after the first study drug administration following randomization and ending 2 days after the study drug was stopped. Hazard ratios (HRs) compared with the vitamin K antagonist (VKA) group are based on the Cox proportional hazards model. Rehospitalizations do not include first index event hospitalization. Log-rank P values compared with the VKA group are based on the 2-sided log-rank test. ARR indicates absolute risk reduction; NNT, number needed to treat; Riva+DAPT, rivaroxaban 2.4 mg twice daily plus background dual antiplatelet therapy with low-dose aspirin; and Riva+P2Y₁₂, rivaroxaban 15 mg once daily+P2Y₁₂ inhibitor.