1460Effect of the INR stability characteristics on bleeding events among atrial fibrillation patients undergoing percutaneous coronary intervention: insights from the PIONEER AF-PCI trial

Abstract

Background: The PIONEER AF-PCI trial demonstrated a reduction in clinically significant bleeding events associated with rivaroxaban in comparison to a vitamin K antagonist (VKA) based strategy among atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI). It is unclear whether this finding remains consistent when VKA-treated patients achieved adequate INR control. Purpose: To compare the occurrence of clinically significant bleeding events among subjects administered rivaroxaban to subjects administered a VKA based regimen stratified by Time in Therapeutic Range (TTR) and time spent with an INR>3. Methods: In the PIONEER AF-PCI trial, 2124 stented AF subjects were randomized to three groups: Group 1) rivaroxaban 15 mg od plus a P2Y12 inhibitor (N=709); Group 2) rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT) (N=709); and Group 3) VKA plus DAPT (N=706). TTR and % of time spend with an INR>3 were calculated using the Rosendaal's method of linear interpolation. Subjects in the VKA group were stratified according to the HAS-BLED score INR lability definition (<60%, ≥60%) and the % of time spend with an INR>3 (0%, <10%, between 10 and 19%, ≥20%). Kaplan-Meier estimates were calculated for significant bleeding through one year (a composite of major, minor bleeding or bleeding requiring medical attention according to Thrombolysis in Myocardial Infarction criteria) through one year and hazard ratios (HR) with 95% confidence intervals were derived using Cox Proportional Hazards models. Log-rank p-values were reported. Results: Among Group 3, 651 (93.4%) subjects had received a least one dose of VKA and had a TTR recorded (TTR <60% = 411, TTR ≥60% = 240). Both Group 1 and Group 2 were associated with a significant decrease in the occurrence of bleeding compared to Group 3 TTR<60% (HR=0.53, 95% CI: 0.39- 0.73, p<0.001; HR=0.57, 95% CI: 0.42-0.78, p<0.001; respectively) and Group 3 TTR ≥60% (HR=0.71, 95% CI: 0.53-0.93, p=0.013; HR=0.76, 95% CI: 0.57- 0.99, p=0.043; respectively). Moreover, 134 (20.6%) subjects had 0% time with an INR>3, 235 (36.1%) had 0-9% time with an INR>3, 139 (21.4%) had 10-19% time with an INR>3, and 143 (22.0%) had ≥20% time with an INR>3. Both Group 1 and Group 2 were associated with a significant reduction in bleeding compared to all subjects in Group 3 regardless of percent time spent with an INR >3 (HR ranges 0.59 to 0.67, and 0.42 to 0.69, respectively). Conclusion: Among AF patient undergoing PCI, rivaroxaban-based strategies decrease the rate of clinically significant bleeding events regardless of the TTR or the time spent with an INR>3. (Figure Presented) .