Rivaroxaban plus aspirin versus with aspirin in
patients with prior percutaneous coronary
Intervention (PCI): Insights from the COMPASS
Trial
Kevin R. Bainey1, Scott D. Berkowitz2, Deepak L. Bhatt3, John W. Eikelboom4, Keith A.
Fox5, Basil S. Lewis6, Tamara Marsden7, Eva Muehlhofer8, Dragos Vinereanu9, Petr
Widimsky10, Robert C. Welsh1
1MazankowskiAlberta Heart Institute, University of Alberta, Edmonton, AB, Canada; 2Bayer U.S., LLC,
Whippany, NJ, USA; 3Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School
Boston, MA, USA; 4McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; 5Department
of Medicine, University of Edinburgh, Edinburgh, UK; 6Lady Davis Carmel Medical Center, Haifa, Israel;
7Population Health Research Institute, Hamilton, ON, Canada; 8Bayer AG, Wuppertal, Germany; 9University
of Medicine and Pharmacy Carol Davila, Bucharest, Romania; 10Charles University, Prague, Czech Republic
Clinical Trial Registration: NCT01776424 American Heart Association Scientific Sessions 2019
PCI
Background
• The COMPASS trial demonstrated dual pathway inhibition (DPI) with rivaroxaban
2.5 mg twice-daily plus aspirin 100 mg once-daily versus aspirin 100 mg once-
daily reduced the primary MACE outcome of cardiovascular death, MI, or stroke
as well as mortality in patients with chronic coronary syndromes or peripheral
artery disease.
• Patients undergoing PCI are routinely treated with DAPT
• However, the efficacy of DPI with prior PCI is less well studied
DAPT=dual antiplatelet therapy; MACE=major adverse cardiac event; MI=myocardial infarction; PCI=percutaneous coronary intervention
PCI
Objectives
• In a pre-specified sub-group analysis from COMPASS, we examined
the impact of dual pathway inhibition compared to aspirin alone in
chronic coronary syndrome patients with or without prior PCI.
• Among patients with a prior PCI, we studied the effects of treatment
according to the timing of prior PCI.
PCI=percutaneous coronary intervention
PCI
Study Flow
COMPASS PCI
16, 560 chronic coronary syndrome patients
Prior PCI No Prior PCI
(n=9862, 59.6%) (n=6698, 40.4%)
DPI Aspirin DPI Aspirin
(n=4963, 50.3%) (n=4899, 49.7%) (n=3342, 49.9%) (n=3356, 50.1%)
Baseline Characteristics PCI
Prior PCI No Prior PCI
(n=9862) (n=6698)
Age, years 68·2 (7·8) 68·5 (7·9)
Female sex 1918 (19·4%) 1461 (21·8%)
Risk factors
Cholesterol, mmol/L 4·1 (1·0) 4·2 (1·1)
Tobacco use 2082 (21·1%) 1281 (19·1%)
Hypertension 7352 (74·5%) 5133 (76·6%)
Peripheral arterial disease 1731 (17·6%) 1563 (23·3%)
Diabetes 3516 (35·7%) 2558 (38·2%)
Previous MI 7372 (74·8%) 3993 (59·6%)
Previous stroke 267 (2·7%) 280 (4·2%)
Medication
ACE inhibitor or ARB 7266 (73·7%) 4636 (69·2%)
Beta-blocker 7304 (74·1%) 4964 (74·1%)
Lipid-lowering agent 9250 (93·8%) 5977 (89·2%)
Data are mean (SD) or n (%). eGFR=estimated glomerular filtration rate. MI=myocardial infarction. ACE inhibitor=angiotensin-converting enzyme inhibitor. ARB=angiotensin
receptor blocker
Prior PCI characteristics according to PCI
treatment received
Low-dose rivaroxaban
plus aspirin Aspirin alone
PCI Occurrence (n=4963) (n=4899)
Timing of prior PCI
Less than one year prior to randomization 249 (5·0%) 231 (4·7%)
1 year to <2 years prior to randomization 1008 (20·3%) 897 (18·3%)
2 years to <3 years prior to randomization 616 (12·4%) 663 (13·5%)
3 years or more prior to randomization 3089 (62·2%) 3105 (63·4%)
PCI type
Single-vessel PCI 3016 (60·8%) 3071 (62·7%)
Multi-vessel PCI 1947 (39·2%) 1828 (37·3%)
Data are n (%). PCI=percutaneous coronary intervention.
Primary Efficacy Endpoint PCI
CV death, MI or stroke (ITT)
Prior PCI Interaction p=0.85 No Prior PCI
HR 0.74 HR 0.76
(95% CI 0.61-0.88) (95% CI 0.61-0.94)
Secondary Efficacy Endpoint PCI
All-Cause Death (ITT)
Prior PCI Interaction p=0.59 No Prior PCI
HR 0.73 HR 0.80
(95% CI 0.58-0.92) (95% CI 0.64-1.00)
Safety Endpoint PCI
Major Bleeding*
Prior PCI
Major Bleed, Previous PCI
Interaction p=0.68 No Prior PCI
Major Bleed, No PCI
0.14
0.14
# at Risk # at Risk
0 1 2 3 0 1 2 3
4963 4346 2216 406 DPI 3342 2839 1412 221 DPI
0.12
0.12
4899 4319 2298 427 ASA Alone 3356 2859 1392 226 ASA Alone
0.10
0.10
Cumulative Incidence Risk
Cumulative Incidence Risk
DPI DPI
ASA Alone ASA Alone
0.08
0.08
HR 1.72 HR 1.58
0.06
0.06
(95% CI 1.34-2.21) (95% CI 1.15-2.17)
0.04
0.04
0.02
0.02
0.0
0.0
0 1y 2y 3y 0 1y 2y 3y
Follow-up Time Follow-up Time
*The primary safety outcome was modified International Society of Thrombosis and Hemostasis (ISTH) major bleeding, defined as: i) fatal bleeding and/or ii) symptomatic bleeding in a critical area
or organ or bleeding into the surgical site requiring re-operation and/or iii) bleeding leading to hospitalization (including presentation to an acute care facility without an overnight stay).
Symptomatic bleeding into a critical organ or area included intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome.
PCI
Other Bleeding Endpoints
Low-dose rivaroxaban Aspirin
plus aspirin alone Low-dose rivaroxaban plus aspirin vs·
(n=8305) (n=8255) aspirin alone
Subgroup Patients with Subgroup Patients with HR P value for
Event Subgroup n events (%) n events (%) (95% CI) interaction
Major Bleed Prior PCI 4963 165 (3·3%) 4899 96 (2·0%) 1·72 (1·34-2·21) 0·68
Major Bleed No prior PCI 3342 98 (2·9%) 3356 62 (1·8%) 1·58 (1·15-2·17) ·
Minor Bleed Prior PCI 4963 489 (9·9%) 4899 291 (5·9%) 1·71 (1·48-1·98) 0·74
Minor Bleed No prior PCI 3342 284 (8·5%) 3356 162 (4·8%) 1·78 (1·47-2·16) ·
Fatal Bleed Prior PCI 4963 7 (0·1%) 4899 2 (<0.1%) 3·47 (0·72-16·7) 0·15
Fatal Bleed No prior PCI 3342 7 (0·2%) 3356 8 (0·2%) 0·87 (0·32-2·41) ·
ICH Bleed Prior PCI 4963 17 (0·3%) 4899 13 (0·3%) 1·30 (0·63-2·68) 0·52
ICH Bleed No prior PCI 3342 9 (0·3%) 3356 10 (0·3%) 0·89 (0·36-2·20) ·
Data are n (%) or HR (95% CI). HR=hazard ratio. PCI=percutaneous coronary intervention. ICH=intracranial hemorrhage
Benefit of DPI vs Aspirin PCI
as a function of time from the most recent percutaneous
coronary intervention
CV Death, MI, Stroke All-cause mortality
The p-value of interaction between treatment group and time since percutaneous The p-value of interaction between treatment group and time since percutaneous
coronary intervention was 0.66 coronary intervention was greater than 0.99
PCI
Conclusions
• DPI compared with aspirin alone:
• Produced consistent reductions in CV death, MI, stroke as well as all-cause
death with or without prior PCI
• Increased major bleeding without a significant increase in fatal bleeding or
intracranial hemorrhage
• In patients with prior PCI:
• Consistent reductions in CV death, MI, stroke as well as all-cause death were
demonstrated with DPI irrespective of the timing of prior PCI (as far back as
10-years)
