J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8

ª 2 0 1 8 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N

P U B L I S H E D B Y E L S E V I E R

CORONARY

Effect of Procedure and CoronaryLesion Characteristics on ClinicalOutcomes Among Atrial FibrillationPatients Undergoing PercutaneousCoronary Intervention

Insights From the PIONEER AF-PCI Trial

Mathieu Kerneis, MD,a C. Michael Gibson, MS, MD,a Gerald Chi, MD,a Roxana Mehran, MD,b Fahad AlKhalfan, MD,a

Usama Talib, MD,a Seyedmahdi Pahlavani, MD,a Mahshid Mir, MD,a Christoph Bode, MD,c Jonathan L. Halperin, MD,b

Tarek Nafee, MD,a Eric D. Peterson, MD, MPH,d Freek W.A. Verheugt, MD,e Peter Wildgoose, PHD,f

Martin van Eickels, MD,g Gregory Y.H. Lip, MD,h,i Keith A.A. Fox, MBCHB,j,k Marc Cohen, MDl

JACC: CARDIOVASCULAR INTERVENTIONS CME/MOC

This article has been selected as this issue’s CME/MOC activity, available

online at http://www.acc.org/jacc-journals-cme by selecting the JACC

Journals CME/MOC tab.

Accreditation and Designation Statement

The American College of Cardiology Foundation (ACCF) is accredited by

the Accreditation Council for Continuing Medical Education (ACCME) to

provide continuing medical education for physicians.

The ACCF designates this Journal-based CME/MOC activity for a maximum

of 1 AMA PRA Category 1 Credit(s). Physicians should only claim credit

commensurate with the extent of their participation in the activity.

Method of Participation and Receipt of CME/MOC Certificate

To obtain credit for this CME/MOC activity, you must:

1. Be an ACC member or JACC: Cardiovascular Interventions

subscriber.

2. Carefully read the CME/MOC-designated article available online and

in this issue of the journal.

3. Answer the post-test questions. At least 2 out of the 3 questions

provided must be answered correctly to obtain CME/MOC credit.

4. Complete a brief evaluation.

5. Claim your CME/MOC credit and receive your certificate electronically

by following the instructions given at the conclusion of the activity.

CME/MOC Objective for This Article: At the end of the activity the reader

should be able to: 1) identify the risks associated with vitamin K antag-

onist based triple therapy (vitamin K antagonist þ aspirin þ P2Y12 in-

hibitors) compared to rivaroxaban-based regimen (rivaroxaban 15 mg þP2Y12 inhibitors or rivaroxaban 2.5 mg þ P2Y12 inhibitor þ aspirin) among

atrial fibrillation patients undergoing percutaneous coronary interven-

tion; 2) recognize the absence of the effect modification of percutaneous

coronary intervention procedure characteristics on the outcomes

ISSN 1936-8798/$36.00

associated with the different antithrombotic strategies evaluated in the

PIONEER AF PCI trial; and 3) appraise the mechanism of action of each

antithrombotic therapy.

CME/MOC Editor Disclosure: JACC: Cardiovascular Interventions CME/MOC

Editor Bill Gogas, MD, PhD, has reported that he has no disclosures.

Author Disclosures: The PIONEER AF-PCI trial was supported by Janssen

Scientific Affairs and Bayer, the sponsors of the study. Dr. Kerneis has

received research grant support from Sanofi, Institut Servier, and

Federation Française de Cardiologie; and has received consulting fees

from Bayer and AstraZeneca. Dr. Gibson has received research grant

support fromJohnson& Johnson, Janssen, andPortola; andhas served as a

consultant for Janssen and Bayer. Dr. Chi has received institutional

research grant support from Portola, Bayer, and Janssen Research. Dr.

Mehran has received consulting fees paid to her institution from Abbott

Laboratories, CardioKinetix, and Spectranetics; has a spouse that has

served as a consultant for Abiomed and The Medicines Company; has

received institutional research funding from AstraZeneca, Bayer, Beth

Israel Deaconness, Bristol-Myers Squibb, CSL Behring, and Eli Lilly/Daiichi

Sankyo; has served as a consultant for Boston Scientific, Shanghai

BraccoSine Pharmaceutical, CSL Behring, and Medscape; has received

advisory board funding to the institution from Bristol-Myers Squibb; has

received a medical monitor paid to the institution from Claret Medical;

owns equity in Claret Medical and Elixir Medical; has served on the

executive committee for Janssen Pharmaceuticals, Osprey Medical; and

has served on the data safety and monitoring board for Watermark. Dr.

Bode has received consulting fees from Bayer, Boehringer Ingelheim,

Daiichi Sankyo, and Bristol-Myers Squibb. Dr. Halperin has served as a

consultant for Bayer Healthcare Pharmaceuticals, Ortho-McNeil-Janssen,

Boehringer Ingelheim, Pfizer, and Medtronic. Dr. Peterson has received

research support from and is a consultant for Janssen. Dr. vanEickels owns

stock (<$10,000) from Bayer. Dr. Lip has served as a consultant for

Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic,

https://doi.org/10.1016/j.jcin.2017.11.009

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8 Kerneis et al.A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4 Impact of PCI Characteristics in PIONNER AF-PCI

627

Boehringer Ingelheim, Microlife, and Daiichi Sankyo; and has served as a

speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer

Ingelheim, Microlife, Roche, and Daiichi Sankyo. Dr. Fox has received

grants from Bayer/Janssen; and honoraria Bayer/Janssen, AstraZeneca,

and Sanofi/Regeneron. Dr. Cohen has served on the Speakers Bureau and

on the advisory board for Janssen. All other authors have reported that

they have no relationships relevant to the contents of this paper to

disclose.

From the aDivision of Cardiovascular Medicine, Department of Medicine, Be

School, Boston, Massachusetts; bCardiovascular Institute, Mount Sinai Medic

New York, New York; cHeart Center, Department for Cardiology and Angiolog

Clinical Research Institute, Durham, North Carolina; eOnze Lieve Vrouwe Gas

Pharmaceuticals, Inc., Beerse, Belgium; gBayer Pharmaceuticals, Inc., Berl

University of Birmingham, Birmingham, United Kingdom; iAalborg Thrombo

Aalborg University, Aalborg, Denmark; jCentre for Cardiovascular Science, UnkRoyal Infirmary of Edinburgh, Edinburgh, United Kingdom; and the lDivisio

Newark, New Jersey. The PIONEER AF-PCI trial was supported by Janssen Sc

Dr. Kerneis has received research grant support from Sanofi, Institut Servie

received consulting fees from Bayer and AstraZeneca. Dr. Gibson has receiv

Janssen, and Portola; and has served as a consultant for Janssen and Baye

support from Portola, Bayer, and Janssen Research. Dr. Mehran has received

Laboratories, CardioKinetix, and Spectranetics; has a spouse that has serve

Company; has received institutional research funding from AstraZeneca, Baye

Behring, and Eli Lilly/Daiichi Sankyo; has served as a consultant for Boston

Behring, and Medscape; has received advisory board funding to the institutio

monitor paid to the institution from Claret Medical; owns equity in Claret Me

committee for Janssen Pharmaceuticals, Osprey Medical; and has served on t

Dr. Bode has received consulting fees from Bayer, Boehringer Ingelheim, Da

has served as a consultant for Bayer Healthcare Pharmaceuticals, Ortho-

Medtronic. Dr. Peterson has received research support from and is a consultan

from Bayer. Dr. Lip has served as a consultant for Bayer/Janssen, Bristol-My

Ingelheim, Microlife, and Daiichi Sankyo; and has served as a speaker for B

ringer Ingelheim, Microlife, Roche, and Daiichi Sankyo. Dr. Fox has receive

Janssen, AstraZeneca, and Sanofi/Regeneron. Dr. Cohen has served on the Sp

All other authors have reported that they have no relationships relevant to

Manuscript received October 16, 2017; revised manuscript received Novemb

Medium of Participation: Print (article only); online (article

and quiz).

CME/MOC Term of Approval

Issue Date: April 9, 2018

Expiration Date: April 8, 2019

th Israel Deaconess Medical Center, Harvard Medical

al Center, Icahn School of Medicine at Mount Sinai,

y I, University of Freiburg, Freiburg, Germany; dDuke

thuis (OLVG), Amsterdam, the Netherlands; fJanssen

in, Germany; hInstitute of Cardiovascular Sciences,

sis Research Unit, Department of Clinical Medicine,

iversity of Edinburgh, Edinburgh, United Kingdom;

n of Cardiology, Newark Beth Israel Medical Center,

ientific Affairs and Bayer, the sponsors of the study.

r, and Federation Française de Cardiologie; and has

ed research grant support from Johnson & Johnson,

r. Dr. Chi has received institutional research grant

consulting fees paid to her institution from Abbott

d as a consultant for Abiomed and The Medicines

r, Beth Israel Deaconness, Bristol-Myers Squibb, CSL

Scientific, Shanghai BraccoSine Pharmaceutical, CSL

n from Bristol-Myers Squibb; has received a medical

dical and Elixir Medical; has served on the executive

he data safety and monitoring board for Watermark.

iichi Sankyo, and Bristol-Myers Squibb. Dr. Halperin

McNeil-Janssen, Boehringer Ingelheim, Pfizer, and

t for Janssen. Dr. van Eickels owns stock (<$10,000)

ers Squibb/Pfizer, Biotronik, Medtronic, Boehringer

ayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boeh-

d grants from Bayer/Janssen; and honoraria Bayer/

eakers Bureau and on the advisory board for Janssen.

the contents of this paper to disclose.

er 8, 2017, accepted November 9, 2017.

Kerneis et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8

Impact of PCI Characteristics in PIONNER AF-PCI A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4

628

Effect of Procedure and CoronaryLesion Characteristics on Clinical OutcomesAmong Atrial Fibrillation Patients UndergoingPercutaneous Coronary Intervention

Insights From the PIONEER AF-PCI Trial

Mathieu Kerneis, MD,a C. Michael Gibson, MS, MD,a Gerald Chi, MD,a Roxana Mehran, MD,b Fahad AlKhalfan, MD,a

Usama Talib, MD,a Seyedmahdi Pahlavani, MD,a Mahshid Mir, MD,a Christoph Bode, MD,c Jonathan L. Halperin, MD,b

Tarek Nafee, MD,a Eric D. Peterson, MD, MPH,d Freek W.A. Verheugt, MD,e Peter Wildgoose, PHD,f

Martin van Eickels, MD,g Gregory Y.H. Lip, MD,h,i Keith A.A. Fox, MBCHB,j,k Marc Cohen, MDl

ABSTRACT

OBJECTIVES This study sought to assess whether there were significant interactions of procedural access strategies

and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with

rivaroxaban or warfarin following a percutaneous coronary intervention.

BACKGROUND Among stented AF patients, the impact of procedural access strategies or lesion characteristics on

antithrombotic safety and efficacy outcomes is unclear.

METHODS In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment

Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial

Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and

followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (n¼ 709); 2) rivaroxaban 2.5 mg twice a day

plus dual antiplatelet therapy (DAPT) (n¼ 709); and 3) dose-adjusted warfarin plus DAPT (n¼ 706). Kaplan-Meier rates of

clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by

subgroups of procedure type and lesion characteristics.

RESULTS Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across

subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on

major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of

revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of

stent or number of stents (interaction p > 0.05 for all subgroups).

CONCLUSIONS Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification

by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events.

Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or

arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban

[JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo

Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543) (J Am Coll Cardiol Intv 2018;11:626–34)

© 2018 by the American College of Cardiology Foundation.

T he recent randomized controlled trials,PIONEER AF-PCI (An Open-label, Random-ized, Controlled, Multicenter Study Exploring

Two Treatment Strategies of Rivaroxaban and aDose-Adjusted Oral Vitamin K Antagonist TreatmentStrategy in Subjects With Atrial Fibrillation WhoUndergo Percutaneous Coronary Intervention) andREDUAL PCI (Evaluation of Dual Therapy With

Dabigatran vs. Triple Therapy With Warfarin inPatients With Atrial Fibrillation That Undergo aPercutaneous Coronary Intervention With Stenting)trials, have demonstrated that triple antithrombotictherapy, with a vitamin K antagonist (VKA), aspirin,and a P2Y12 inhibitor, is associated with a greater rateof major hemorrhage compared with either dualantithrombotic therapy with non–vitamin K

TABLE 1 Procedure and Lesion Characteristics

Overall(N ¼ 2,099)

Group 1(n ¼ 696)

Group 2(n ¼ 706)

Group 3(n ¼ 697)

Revascularization

Ischemia driven 1,155 (55.0) 376 (54.0) 400 (56.7) 379 (54.4)

Urgent 811 (38.6) 279 (40.1) 279 (39.5) 253 (36.3)

Arterial approach

Radial 1,332 (63.5) 430 (61.8) 449 (63.6) 453 (65.0)

Femoral 758 (36.1) 263 (37.8) 254 (36.0) 241 (34.4)

Vascular closure device 558 (26.6) 187 (26.9) 189 (26.8) 182 (26.1)

Coronary lesions

Single-vessel disease

LAD 732 (34.9) 235 (33.8) 251 (35.6) 246 (35.3)

Cx 342 (16.3) 128 (18.4) 112 (15.9) 102 (14.6)

RCA 534 (25.4) 172 (24.7) 177 (25.1) 185 (26.5)

Multivessel disease 394 (18.8) 130 (18.7) 133 (18.8) 131 (18.8)

Presence of thrombus 125 (6.0) 44 (6.3) 38 (5.4) 43 (6.2)

Stenosis >70% or thrombus 1,678 (79.9) 560 (80.5) 558 (79) 560 (80.3)

Bifurcation 216 (10.3) 62 (8.9) 78 (11) 76 (10.9)

Stents

Type

Drug-eluting stent 1,383 (65.9) 452 (64.9) 468 (66.3) 463 (66.4)

Bare-metal stent 671 (32.0) 230 (33.0) 220 (31.2) 221 (31.7)

Length

>40 mm 375 (17.9) 112 (16.1) 128 (18.1) 135 (19.4)

31–40 mm 273 (13.0) 95 (13.6) 97 (13.7) 81 (11.4)

21–30 mm 550 (26.2) 201 (28.9) 170 (24.1) 179 (25.7)

<20 mm 897 (42.7) 287 (41.2) 310 (43.9) 300 (43.0)

Number

1 1,388 (66.1) 454 (65.2) 459 (65) 475 (68.1)

>2 709 (33.8) 242 (24.8) 246 (34.8) 221 (31.7)

Values are n (%). Group 1 ¼ low-dose rivaroxaban plus P2Y12 inhibitors; Group 2 ¼ very low-dose rivaroxabanplus dual antiplatelet therapy for 1, 6, 12 months; Group 3 ¼ standard vitamin K antagonist–based triple therapyfor 1, 6, 12 months.

Cx ¼ circumflex artery; LAD ¼ left anterior descending artery; RCA ¼ right coronary artery.

ABBR EV I A T I ON S

AND ACRONYMS

ACS = acute coronary

syndrome

AF = atrial fibrillation

CI = confidence interval

DAPT = dual antiplatelet

therapy

DES = drug-eluting stent(s)

HR = hazard ratio

NOAC = non–vitamin K oral

anticoagulants

PCI = percutaneous coronary

intervention

VKA = vitamin K antagonist

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8 Kerneis et al.A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4 Impact of PCI Characteristics in PIONNER AF-PCI

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anticoagulants (NOACs) plus a P2Y12 inhibitor or a verylow dose of rivaroxaban plus dual antiplatelet therapy(DAPT) in atrial fibrillation (AF) patients undergoingpercutaneous coronary intervention (PCI) withstenting (1,2). In addition, both NOAC-based strategieshave resulted in a similar rate of ischemic eventscompared with the standard triple therapy.

It remains, however, unclear whether procedureaccess strategy, stenting strategy, or lesion character-istics would affect the safety or efficacy outcomesassociatedwith different antithrombotic strategies. Theaim of the present analysis was to examine the inter-action of procedural or coronary lesion characteristicswith bleeding and ischemic events among AF subjectsundergoing PCI enrolled in the international, random-ized, PIONEER AF-PCI trial.

METHODS

STUDY DESIGN AND POPULATION. The design andthe results of the PIONEER AF-PCI trial (NCT01830543)have been previously published (1,3). Briefly, 2,124participants with paroxysmal, persistent, or perma-nent nonvalvular AF who had undergone PCI withstenting were randomly assigned, within 72 h ofsheath removal, in a 1:1:1 ratio, to receive: 1) rivarox-aban 15 mg once daily plus a P2Y12 inhibitor for 12months (Group 1); 2) rivaroxaban 2.5 mg twice dailyplus DAPT for 1, 6, or 12 months (Group 2); or 3) stan-dard therapy with a dose-adjusted vitamin K antago-nist plus DAPT for 1, 6, or 12 months (Group 3). Majorexclusion criteria were: 1) a history of stroke or tran-sient ischemic attack; 2) clinically significant gastro-intestinal bleeding within 12 months beforerandomization; 3) a calculated creatinine clearanceof <30 ml/min, anemia of an unknown cause with ahemoglobin concentration of <100 g/l, or any condi-tion known to increase the risk of bleeding; 4) stentplacement during the index hospitalization for in-stent restenosis; and 5) stent thrombosis during theindex hospitalization.

STUDY ENDPOINTS. The primary safety endpointwas the occurrence of clinically significant bleeding (acomposite of major or minor bleeding or bleedingrequiring medical attention according to Thrombol-ysis In Myocardial Infarction criteria) (4) duringthe treatment period (defined as the time from thefirst administration of a trial drug to 2 days after thetrial drugs were discontinued, through 12 months oftherapy). The efficacy endpoint was the occurrenceof a major adverse cardiovascular event (a compositeof death from cardiovascular causes, myocardialinfarction, or stroke). All events were adjudicated

SEE PAGE 635

by an independent committee blinded totreatment assignment.

STATISTICAL ANALYSIS. The effect modifi-cation by either procedure or lesion char-acteristics on the safety and efficacyendpoints was assessed with the joint testin a Cox proportional hazards model. Threespecific pairwise comparisons were per-formed (Group 1 vs. Group 3, Group 2 vs.Group 3, and Group 1 combined with Group2 vs. Group 3) without adjusting for multi-plicity. All analyses were done by an aca-demic research organization, PERFUSE(Percutaneous-Pharmacologic EndoluminalRevascularization for Unstable SyndromesEvaluation) using a copy of the Study Data

Tabulation Model database. Stratification was basedon subgroups of PCI procedure and coronary lesioncharacteristics including arterial approach, setting of

FIGURE 1 Safety Outcomes by Procedure and Lesion Characteristics and Treatment Group

Group 1 (15 mg once daily [od] rivaroxaban plus P2Y12 inhibitors) versus Group 3 (standard vitamin K antagonist [VKA]–based triple therapy for

1, 6, or 12 months). BMS ¼ bare-metal stent(s); CI ¼ confidence interval; Cx ¼ circumflex artery; DES ¼ drug-eluting stent(s); HR ¼ hazard

ratio; LAD ¼ left anterior descending artery; MVD ¼ multivessel disease; RCA ¼ right coronary artery.

Kerneis et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8

Impact of PCI Characteristics in PIONNER AF-PCI A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4

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the revascularization (i.e., urgent revascularizationfor acute coronary syndrome [ACS] patient or plan-ned procedure for stable patients), location ofculprit artery, presence of bifurcation lesion, pres-ence of thrombus, and the type, length, and numberof stents. This analysis was based on the modifiedintention-to-treat population of the PIONEER AF-PCItrial, including all participants who underwentrandomization and received at least 1 dose of a trialdrug during the treatment period.

RESULTS

PROCEDURE AND LESION CHARACTERISTICS.

The baseline demographic characteristics of thePIONEER AF-PCI trial have been already described (1).Briefly, the mean age was 70 years of age, 3 of 4subjects were white men and one-half of the subjectswere enrolled after an ACS. Of interest, among the2,099 patients randomized that had received at least 1

dose of the trials drugs, 125 (6.0%) subjects had thepresence of thrombus detected, 216 (10.3%) hadbifurcation lesions, 811 (38.3%) were urgently revas-cularized, and 709 (33.8%) had 2 stents or more.Finally, drug-eluting stents (DES) were used among1,383 (65.9%) subjects. The detail of the procedureand lesion characteristics among the 3 differentgroups is summarized in the Table 1.

INTERACTION ON BLEEDING EVENTS. Among sub-jects who had a femoral access (n ¼ 758), rivaroxabanwas associated with a reduced rate of clinically sig-nificant bleeding events compared with VKA-basedtriple therapy (Group 1 vs. Group 3, hazard ratio[HR]: 0.57 [95% confidence interval (CI): 0.37 to 0.85],p ¼ 0.006; Group 2 vs. Group 3, HR: 0.63 [95% CI: 0.42to 0.94], p ¼ 0.02). The reduction of the clinicallysignificant hemorrhage rate was consistent amongsubjects with radial access in both rivaroxaban groupcompared with VKA-based triple therapy (Group 1 vs.

FIGURE 2 Safety Outcomes by Procedure and Lesion Characteristics and Treatment Group

Group 2 (2.5 mg twice daily [bid] rivaroxaban plus dual antiplatelet therapy) versus Group 3 (standard VKA-based triple therapy for 1, 6, or 12

months). Abbreviations as in Figure 1.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8 Kerneis et al.A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4 Impact of PCI Characteristics in PIONNER AF-PCI

631

Group 3, HR: 0.61 [95% CI: 0.45 to 0.82], p ¼ 0.001,p for interaction ¼ 0.96; Group 2 vs. Group 3, HR: 0.64[95% CI: 0.47 to 0.85], p ¼ 0.002, p for interaction ¼1.00). There was no interaction between the use ofvascular closure device and the effect of rivaroxaban(p for interaction ¼ 0.94 and 0.31 in Groups 1 and 2,respectively). There was no other effect modificationby procedure or lesion on the safety endpoint(Figures 1 and 2, Online Figure 1).

INTERACTION ON ISCHEMIC EVENTS. Among sub-ject treated with DES, a rivaroxaban-based strategywas associated with a similar rate of ischemicevents compared with VKA (5.7% and 5.0% vs.5.7%; p ¼ 0.92 and p ¼ 0.63 for Groups 1 and 2,respectively). Treatment effect of rivaroxaban onmajor adverse cardiovascular events did not varysignificantly when stratified by ischemia-drivenrevascularization, urgency of revascularization,location of culprit artery, presence of angiographicstenosis, presence of bifurcation lesion, presence of

thrombus, and type, length, or number of stents(p for interaction >0.05 for all subgroups)(Figures 3 and 4, Online Figure 2).

DISCUSSION

This analysis did not reveal any effect modification ofthe impact of complex coronary lesions, stent char-acteristics, or vascular approach on the results ofeither bleeding or efficacy in the PIONEER AF-PCItrial comparing rivaroxaban with VKA. Moreover,the recommendation to continue a VKA-based tripletherapy up to 6 months among patients with greatrisk of ischemic events (i.e., more than 2 stents,emergency revascularization, or bifurcation) is notsupported by our analysis (5).

In the context of current guidelines, the thera-peutic decision-making process among stented AFpatients is influenced by PCI complexity and fear ofstent thrombosis. These concerns are linked to thelesion characteristics, the presence of a bifurcation

FIGURE 3 Efficacy Outcomes by Procedure and Lesion Characteristics and Treatment Group

Group 2 (15 mg once daily [od] rivaroxaban plus P2Y12 inhibitors) versus Group 3 (standard VKA-based triple therapy for 1, 6, or 12 months).

Abbreviations as in Figure 1.

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632

lesion, and finally the possibility that shorter dura-tions of DAPT may be associated with a greater rateof stent thrombosis and myocardial infarctionamong PCI patients (6,7). Although efficacy dataare limited, cardiologists need to make complexdecisions with limited available data: first, becausestented AF patients are often affected by comor-bidities that are associated with more complexcoronary anatomy (8); second, because oral antico-agulant–requiring patients have been excludedfrom all the PCI studies evaluating the duration ofDAPT after stenting with DES (9). Therefore,bare-metal stent usage had been considered theappropriate choice among patients requiring oralanticoagulants (10). In this study, the rate of theefficacy composite endpoint was similar regardlessof the type of stent (DES or bare-metal stent) or thepresence of complex lesions between the 3 groups.These results provide reassuring data among pa-tients treated with DES, or with an elevatedischemic risk.

The rate of bleeding events was also consistentlyreduced among subjects treated with either rivarox-aban strategy. As there is a considerable overlapamong the risk factors associated with ischemicand bleeding events, these findings suggests the safetyof the rivaroxaban-based strategy among patients forwhom bleeding and ischemic risk coexists (11).

Finally, this analysis is also supported by therecent results of the REDUAL PCI trial (2), becauseone-half of the subjects were randomized in REDUALPCI trial after an ACS and 8 of 10 subjects receivedDES. Moreover, the rate of radial and femoral accesswas similar between both the PIONEER AF-PCI andREDUAL PCI trials. The reduction of bleeding eventsand the similar rate of ischemic events associatedwith dabigatran-based therapy compared with VKAamong this population emphasizes the safety ofNOAC strategies in a modern era, in which DES andradial access are widely used. Two ongoing random-ized controlled trials, AUGUSTUS (An Open-label,2 � 2 Factorial, Randomized Controlled, Clinical Trial

FIGURE 4 Efficacy Outcomes by Procedure and Lesion Characteristics and Treatment Group

Group 2 (2.5 mg twice daily [bid] rivaroxaban plus dual antiplatelet therapy) versus Group 3 (standard VKA-based triple therapy for 1, 6, or 12

months). Abbreviations as in Figure 1.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8 Kerneis et al.A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4 Impact of PCI Characteristics in PIONNER AF-PCI

633

to Evaluate the Safety of Apixaban vs. Vitamin KAntagonist and Aspirin vs. Aspirin Placebo inPatients With Atrial Fibrillation and Acute CoronarySyndrome or Percutaneous Coronary Intervention)(NCT02415400) and ENTRUST-AF-PCI (EdoxabanTreatment Versus Vitamin K Antagonist in PatientsWith Atrial Fibrillation Undergoing PercutaneousCoronary Intervention) (NCT02866175) will evaluatethe safety and the efficacy of 2 other NOACs, apixabanand edoxaban, among AF patients undergoing PCIand provide further information to support the use ofNOAC-based strategies.

STUDY LIMITATIONS. First, these are subgroupanalyses and should, therefore, be interpreted withcaution, as they are by definition underpowered incomparison with the overall trial results. The low ab-solute number of events among patients with

presence of thrombus or bifurcation may have limitedthe statistical power of this analysis. However, theresults remain consistent when combining the 2rivaroxaban groups. Second, as the PIONEER AF-PCItrial was not powered for efficacy, the post hoc anal-ysis of the ischemic endpoint cannot solely informdecision making in patients who are considered athigh anatomic risk. Third, as the subjects were ran-domized within the first 72 h following the sheathremoval once the international normalized ratiowas #2.5, the periprocedural antithrombotic regimen,as the intravenous anticoagulant or the administra-tion of aspirin in the group 1, was not considered inthis analysis. Finally, the radial approach should leadto fewer in-hospital bleeding and vascular complica-tions than should the femoral approach (12,13), but thechoice of radial or femoral approach was notrandomized.

PERSPECTIVES

WHAT IS KNOWN? Rivaroxaban-based therapy is

superior to warfarin plus DAPT in bleeding outcomes

among AF-stented patients.

WHAT IS NEW? There was no effect modification of

rivaroxaban-based therapy by procedure or lesion

characteristics on either clinically significant bleeding

or major adverse cardiovascular events.

WHAT IS NEXT? Pooled analysis of current and

future trials in AF patients undergoing PCI would

provide powered evidence to evaluate the efficacy of

NOAC-based strategy compared with VKA-based tri-

ple therapy.

Kerneis et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 7 , 2 0 1 8

Impact of PCI Characteristics in PIONNER AF-PCI A P R I L 9 , 2 0 1 8 : 6 2 6 – 3 4

634

CONCLUSIONS

Among AF patients undergoing stent placement ran-domized in the PIONEER AF-PCI trial, no effectmodification was observed by either procedure orlesion characteristics on clinically significantbleeding or major adverse cardiovascular events.Rivaroxaban-based therapy was superior to warfarinplus DAPT in bleeding outcomes regardless of thevascular access approach, and similar to warfarin plusDAPT in ischemic outcomes regardless of the type,length, and number of stents.

ADDRESS FOR CORRESPONDENCE: Dr. C. MichaelGibson, Beth Israel Deaconess Medical Center, Cardio-vascular Division, 20 Overland Street, Boston, Massa-chusetts 02215. E-mail: mgibson@bidmc.harvard.edu.

RE F E RENCE S

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KEY WORDS atrial fibrillation, coronaryartery, percutaneous coronary intervention,randomized controlled trials as topic,rivaroxaban

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