Risk of myocardial infarction in paroxysmal vs. non-paroxysmal atrial fibrillation: an individual patient-level data analysis of 71,466 patients from COMBINE AF
Abstract Body (Do not enter title and authors here): Background: Prior data suggest the MI risk may be higher with paroxysmal AF (PAF) vs. non-paroxysmal AF (non-PAF). Proposed mechanisms include tachycardia-induced oxidative stress (via LOX-1) with microvascular flow abnormalities, ischemia downstream of a fixed coronary obstruction, and plaque rupture. Methods: We compared MI rates in pts with PAF vs. non-PAF in COMBINE AF, a patient-level metanalysis of 4 RCTS of DOACs vs warfarin (ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY,ROCKET AF). Secondary endpoints were ischemic stroke and CV death. Cox proportional-hazards models stratified by trial and adjusted for elements of the CHADS-VASc score were constructed. Sensitivity analyses were performed across subgroups, omitting pts on lower-dose DOAC regimens, and accounting for competing risk of death. Results: Of 71,466 pts, 16,609 (23%) had PAF at enrollment. Pts with PAF vs non-PAF were similar age (median 72 vs 72. P=0.15), but more likely women (43 vs 36%), with prior CAD (35 vs 31%), and on aspirin (41 vs 32%); but less likely Asian race (12 vs 15%) or with CHADS-VASc score > 4 (59 vs 60%), p<0.002 for each. During >160,000 pt-yrs of follow-up, 1033 MIs occurred: 277 (1.67%) in pts with PAF vs 766 (1.40%) in pts with non-PAF, corresponding to rates of 0.81% and 0.70% per pt-year. The HRadj for MI with PAF vs non--paroxysmal AF was 1.17 [1.02-1.35], p=0.028 (Fig). Ischemic stroke occurred in 364 (2.19%) vs 1425 (2.60%) pts with PAF vs non--paroxysmal AF (HRadj 0.81 [0.72-0.91], p<0.001). CV death occurred in 625 (3.77%) pts with PAF vs 3027 (5.52%) with non-paroxysmal AF (HRadj 0.75 [0.68-0.81], p<0.001). No significant effect modification of pt characteristics on MI risk by AF pattern were present, although a trend was seen for higher MI risk with PAF vs non-PAF in pts with prior CAD (HR 1.34 [1.12-1.59]) vs no prior CAD (HR 0.96 [0.76-1.22]), PINT 0.06. Results were consistent across trials, by anticoagulant, excluding lower dose DOACs, and accounting for competing mortality risk. Conclusions: This individual patient-level metanalysis of 71,466 pts from COMBINE AF shows that the adjusted risk of MI is higher in pts with PAF than non--paroxysmal AF, while the adjusted risks of ischemic stroke and CV death were lower in pts with PAF.
Ntaios, Georgios
( University of Thessaly
, Katerini
, Hawaii
, United States
)
Granger, Christopher
( DUKE CLINICAL RESEARCH INSTITUTE
, Durham
, North Carolina
, United States
)
Patel, Manesh
( DUKE MEDICAL CENTER
, Durham
, North Carolina
, United States
)
Wallentin, Lars
( UPPSALA CLINICAL RESEARCH CENTRE
, Uppsala
, Sweden
)
Giugliano, Robert
( TIMI Study Group
, Boston
, Massachusetts
, United States
)
Goette, Andreas
( ST VINCENZ KRANKENHAUS
, Paderborn
, Germany
)
Palazzolo, Michael
( TIMI Study Group
, Boston
, Massachusetts
, United States
)
Antman, Elliott
( BRIGHAM WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Ruff, Christian
( BRIGHAM WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Braunwald, Eugene
( TIMI Study Group
, Boston
, Massachusetts
, United States
)
Link, Mark
( UTSouthwestern Medical Center
, Dallas
, Texas
, United States
)
Mahaffey, Kenneth
( Stanford University
, Stanford
, California
, United States
)
Eikelboom, John
( McMaster University HGH
, Hamilton
, Ontario
, Canada
)
Author Disclosures:
Georgios Ntaios:No Answer
| Christopher Granger:DO have relevant financial relationships
;
Consultant:Alnylam:Active (exists now)
; Consultant:Pfizer:Active (exists now)
; Researcher:Boehringer Ingelheim:Past (completed)
; Consultant:Anthos:Active (exists now)
; Researcher:Anthos:Active (exists now)
; Consultant:Boston Scientific:Active (exists now)
; Researcher:Phillips:Active (exists now)
; Consultant:Janssen:Active (exists now)
; Researcher:Amgen:Active (exists now)
; Consultant:Merck:Active (exists now)
; Consultant:Novartis:Active (exists now)
; Consultant:Celecor:Active (exists now)
; Consultant:Roche:Active (exists now)
; Researcher:Roche:Active (exists now)
; Researcher:Alnylam:Active (exists now)
| Manesh Patel:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Bayer:Expected (by end of conference)
; Consultant:Esperion:Past (completed)
; Consultant:Bayer:Active (exists now)
; Research Funding (PI or named investigator):Idorsia:Active (exists now)
; Research Funding (PI or named investigator):Novartis:Active (exists now)
| Lars Wallentin:DO NOT have relevant financial relationships
| Robert Giugliano:No Answer
| Andreas Goette:DO NOT have relevant financial relationships
| Michael Palazzolo:No Answer
| Elliott Antman:DO have relevant financial relationships
;
Researcher:Itamar MEdical:Past (completed)
; Employee:AHA:Active (exists now)
| Christian Ruff:No Answer
| Eugene Braunwald:No Answer
| Mark Link:DO NOT have relevant financial relationships
| Kenneth Mahaffey:DO have relevant financial relationships
;
Research Funding (PI or named investigator):AHA:Active (exists now)
; Research Funding (PI or named investigator):Gilead:Past (completed)
; Consultant:Fuson:Active (exists now)
; Research Funding (PI or named investigator):Ferring:Past (completed)
; Consultant:Elsevier:Past (completed)
; Research Funding (PI or named investigator):Eidos:Active (exists now)
; Research Funding (PI or named investigator):CSL:Active (exists now)
; Consultant:CSL :Past (completed)
; Research Funding (PI or named investigator):California Institute Regenerative Medicine:Past (completed)
; Consultant:BridgeBio:Active (exists now)
; Consultant:BMS:Active (exists now)
; Consultant:Bayer:Active (exists now)
; Research Funding (PI or named investigator):Bayer:Active (exists now)
; Research Funding (PI or named investigator):Apple:Active (exists now)
; Consultant:Applied Therapuetics:Active (exists now)
| John Eikelboom:DO have relevant financial relationships
;
Consultant:Anthos:Active (exists now)
; Speaker:USV:Active (exists now)
; Speaker:Pfizer:Active (exists now)
; Speaker:Merck:Active (exists now)
; Speaker:Janssen:Active (exists now)
; Speaker:Ionis:Active (exists now)
; Speaker:Daiichi-Sankyo:Active (exists now)
; Speaker:BMS:Active (exists now)
; Speaker:BI:Active (exists now)
; Speaker:Bayer:Active (exists now)
Khan Muhammad Aslam, Haider Taimoor, Bhattarai Shraddha, Afzal Hafsa, Khan Bilal, Muhammad Anza, Shafique Nouman, Bhatia Hitesh, Aafreen Asna, Adil Abid Nawaz Khan, Akbar Usman, Khan Alamzaib, Haider Muhammad Adnan
