Effect of Procedure and Coronary Lesion Characteristics on ... · Effect of Procedure and Coronary...
Transcript of Effect of Procedure and Coronary Lesion Characteristics on ... · Effect of Procedure and Coronary...
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 TrialMathieu 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
629
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 ofFIGURE 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
630
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.
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
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: [email protected].
RE F E RENCE S
1. Gibson CM, Mehran R, Bode C, et al. Preventionof bleeding in patients with atrial fibrillation un-dergoing PCI. N Engl J Med 2016;375:2423–34.
2. Cannon CP, Bhatt DL, Oldgren J, et al. Dualantithrombotic therapy with dabigatran after PCIin atrial fibrillation. N Engl J Med 2017;377:1513–24.
3. Gibson CM, Mehran R, Bode C, et al. An open-label, randomized, controlled, multicenter studyexploring two treatment strategies of rivaroxabanand a dose-adjusted oral vitamin K antagonisttreatment strategy in subjects with atrial fibrilla-tion who undergo percutaneous coronary inter-vention (PIONEER AF-PCI). Am Heart J 2015;169:472–8.e5.
4. Mehran R, Rao SV, Bhatt DL, et al. Standardizedbleeding definitions for cardiovascular clinical tri-als: a consensus report from the Bleeding Aca-demic Research Consortium. Circulation 2011;123:2736–47.
5. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESCfocused update on dual antiplatelet therapy incoronary artery disease developed in collaborationwith EACTS: The Task Force for dual antiplatelettherapy in coronary artery disease of the EuropeanSociety of Cardiology (ESC) and of the EuropeanAssociation for Cardio-Thoracic Surgery (EACTS).Eur Heart J 2018;39:213–60.
6. Cayla G, Hulot J-S, O’Connor SA, et al. Clinical,angiographic, and genetic factors associated withearly coronary stent thrombosis. JAMA 2011;306:1765–74.
7. Iakovou I, Schmidt T, Bonizzoni E, et al. Inci-dence, predictors, and outcome of thrombosisafter successful implantation of drug-elutingstents. JAMA 2005;293:2126–30.
8. Kralev S, Schneider K, Lang S, Süselbeck T,Borggrefe M. Incidence and severity of coronaryartery disease in patients with atrial fibrillationundergoing first-time coronary angiography.Biondi-Zoccai G, editor. PLoS One 2011;6:e24964.
9. Palmerini T, Sangiorgi D, Valgimigli M, et al.Short- versus long-term dual antiplatelet therapyafter drug-eluting stent implantation: an individ-ual patient data pairwise and network meta-analysis. J Am Coll Cardiol 2015;65:1092–102.
10. Faxon DP, Eikelboom JW, Berger PB, et al.Antithrombotic therapy in patients with atrialfibrillation undergoing coronary stenting: a NorthAmerican perspective: executive summary. CircCardiovasc Interv 2011;4:522–34.
11. Gallego P, Roldán V, Torregrosa JM, et al.Relation of the HAS-BLED bleeding risk score tomajor bleeding, cardiovascular events, and
mortality in anticoagulated patients with atrialfibrillation. Circ Arrhythm Electrophysiol 2012;5:312–8.
12. Ferrante G, Rao SV, Jüni P, et al. Radial versusfemoral access for coronary interventions acrossthe entire spectrum of patients with coronary ar-tery disease: a meta-analysis of randomized trials.J Am Coll Cardiol Intv 2016;9:1419–34.
13. Andò G, Capodanno D. Radial access reducesmortality in patients with acute coronary syn-dromes: results from an updated trial sequentialanalysis of randomized trials. J Am Coll CardiolIntv 2016;9:660–70.
KEY WORDS atrial fibrillation, coronaryartery, percutaneous coronary intervention,randomized controlled trials as topic,rivaroxaban
APPENDIX For supplemental figures, pleasesee the online version of this paper.
Go to http://www.acc.org/jacc-journals-cme to takethe CME/MOC quiz forthis article.