Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis

Abstract

Aims: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome.

Methods: Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis.

Results: Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024).

Conclusion: After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.

Keywords: Atrial fibrillation; CHA2DS2-VASc; Coronary stenting; Edoxaban; NOACs.

Conflict of interest statement

Andreas Goette discloses honoraria and speaker fees from Astra Zeneca, Bayer Health Care, Berlin-Chemie, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Medtronic, Novartis, and Omeicos. Research has been supported by Josef-Freitag Stiftung and Deutsche Herzstiftung e.V. outside the submitted work. Thorsten Lewalter reports personal fees from Abbott, Boston Scientific, Bayer, Boehringer, Daiichi Sankyo, and Pfizer outside the submitted work. Marco Valgimigli reports grants and personal fees from Abbott, Alvimedica, Amgen, Bayer, Bristol-Myers Squibb SA, Coreflow, Daiichi Sankyo, Vifor, Idorsia, Terumo, and iVascular; grants and personal fees from grants from AstraZeneca and Medicure, outside the submitted work. Lars Eckardt discloses consultant fees, speaking honoraria, and travel expenses from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boehringer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer, and Sanofi Aventis. Research has been supported by German Research Foundation (DFG) and German Heart Foundation outside the submitted work. Petra Laeis, Paul-Egbert Reimitz, Rüdiger Smolnik and Wolfgang Zierhut are employees of Daiichi Sankyo Europe GmbH, Munich, Germany. Jan G. Tijssen reports personal fees from AstraZeneca, Bayer, and Boehringer Ingelheim outside the submitted work. Pascal Vranckx discloses personal fees from Daiichi Sankyo during the conduct of the study; and personal fees from AstraZeneca, Bayer Health Care, CLS Behring, and Terumo outside the submitted work.

Figures

Fig. 1

Time to first major or CRNM bleeding by CHA2DS2-VASc category. CRNM clinically relevant non-major

Fig. 2

Frequency of any stent thrombosis by CHA2DS2-VASc score category

Fig. 3

Major or CRNM bleeding (a), primary efficacy (b), and net clinical benefit outcomes (c) for patients treated with edoxaban- or VKA-based regimen

Fig. 4

Frequency of myocardial infarction by atrial fibrillation subtype. AF, atrial fibrillation; MI, myocardial infarction

Fig. 5

Landmark analysis of net clinical benefit with a landmark set at day 14. Landmark analysis 14 days, 14 days NCB, ITT, overall period + 3 days. ITT intention to treat, HR hazard ratio, NCB net clinical benefit, VKA vitamin K antagonist