ESC Congress 2017 In Review – Focus on CAD&ACS - 10

Late-Breaking Clinical Trials

from ATLAS TIMI-51 by evaluating whether rivaroxaban
plus aspirin or rivaroxaban alone is superior to aspirin
alone for prevention of CV death, stroke, or myocardial
infarction (MI) in patients with stable coronary artery
disease (CAD) or peripheral arterial disease (PAD).
COMPASS recruited a selected high-risk population with
CAD or PAD. The definition of CAD was prior MI, multivessel
coronary disease, or prior coronary revascularisation. The
definition of PAD was prior peripheral revascularisation or
amputation, claudication with a low ankle brachial index or
asymptomatic carotid disease. The population was further
enriched for risk in that patients aged < 65 years who had
also multivessel coronary disease or at least 2 additional
risk factors (diabetes mellitus, smoking, renal dysfunction,
heart failure, or nonlacunar stroke).
The primary outcome was a composite of CV death,
stroke, or MI. Secondary endpoints included the composite of ischaemic stroke, MI, acute limb ischaemia (ALI),
or death from coronary heart disease; the composite
of ischaemic stroke, MI, ALI, or CV death; and death
from any cause. The main safety outcome was a modification of the International Society on Thrombosis and
Haemostasis (ISTH) criteria for major bleeding and the
net clinical benefit was a composite of the primary outcome and fatal or critical organ bleeding.
Between March 2013 and May 2016, 27,395 patients
from 602 centres in 33 countries were randomised (1:1:1)
to treatment with rivaroxaban 2.5 mg BID plus aspirin
100 mg QD, rivaroxaban 5 mg BID, or aspirin 100 mg daily. At baseline, patients were a mean age of 68.2 years
(22% women); 91% had CAD and 27% had PAD. The trial
was stopped at the first formal analysis, as overwhelming
efficacy in favour of rivaroxaban plus aspirin was noted.
Mean follow-up was 23 months and maximum follow-up
was 47 months.
Compared with aspirin alone, rivaroxaban 2.5 mg BID
plus aspirin 100 mg QD significantly reduced the composite rate of CV death, stroke, and MI by 24% (4.1%

Cumulative Risk of Cardiovascular Death,
Stroke, or Myocardial Infarction

Figure 1. Primary Outcome: Cardiovascular Death, Stroke, or
Myocardial Infarction
Rivaroxaban + aspirin vs aspirin HR, 0.76; 95% CI, 0.66-0.86; P = < .001
Rivaroxaban vs aspirin HR, 0.90; 95% CI, 0.79-1.03; P = .12

0.10

0.08

0.06

0.04

Aspirin
Rivaroxaban
Rivaroxaban + Aspirin

0.02

0.0
0

Year

From The New England Journal of Medicine, Eikelboom JW et al, Rivaroxaban
with or without Aspirin in Stable Cardiovascular Disease, EPub 28 August 2017.
Copyright © 2017 Massachusetts Medical Society. Reprinted with permission
from Massachusetts Medical Society.

October 2017

vs 5.4%; HR, 0.76; 95% CI, 0.66 to 0.86; P ≤ .001). The
rivaroxaban 5 mg BID alone arm did not significantly
reduce the primary endpoint (Figure 1). Benefits of the
rivaroxaban 2.5 mg BID plus aspirin arm versus aspirin
alone were generally consistent across the components
of the primary endpoint.
The secondary composite outcomes were significantly
improved with the combination therapy (all P ≤ .01) compared with aspirin alone. There was a trend towards lower
mortality with the rivaroxaban 2.5 mg BID plus aspirin arm
versus aspirin alone (3.4% vs 4.1%; P = .01); however this did
not meet the threshold P value for significance of .0025.
Both rivaroxaban arms caused more major bleeds
than aspirin alone. In the aspirin plus rivaroxaban 2.5 mg
BID arm, major bleeding was increased by 70% (3.1% vs
1.9%; HR, 1.70; 95% CI, 1.40 to 2.05; P < .001) while the
rivaroxaban 2.5 mg BID only arm increased major bleeding by 51% (P < .001). Rates of fatal bleeding or symptomatic intracranial haemorrhage were low and were not significantly increased with rivaroxaban plus aspirin versus
aspirin (HR, 1.23; P = .40); there was a trend toward an
increase with rivaroxaban 5 mg BID alone compared with
aspirin (HR, 1.59; P = .05). Both rivaroxaban arms increased
bleeding leading to transfusion versus aspirin alone (HR,
1.97; P < .001 for rivaroxaban 2.5 mg BID; HR, 1.50; P = .03
for rivaroxaban 5 mg BID).
Overall with rivaroxaban 2.5 mg twice daily added to
aspirin versus aspirin alone over a median of 23 months
there was a 1.3% absolute reduction in the primary
endpoint versus a 1.2% increase in major bleeding. The
prespecified net clinical benefit weighing only fatal or
critical organ bleeding against the primary composite
efficacy outcome was superior for rivaroxaban 2.5 mg
BID with aspirin compared with aspirin alone (4.7% vs
5.9%; HR, 0.80; 95% CI, 0.70 to 0.91; P < .001).
The COMPASS trial demonstrated that in high-risk
patients with CAD and/or PAD rivaroxaban 2.5 mg BID
plus aspirin 100 mg QD reduces the composite of CV
death, stroke, or MI compared with aspirin alone while
rivaroxaban 5 mg BID monotherapy does not. Major
bleeding is increased with rivaroxaban with aspirin or
alone but without a significant increase in fatal, intracranial or critical organ bleeding.

CANTOS Shows Canakinumab
Improves Atherothrombotic
Outcomes and Alters Cancer
Progression
Written by Maria Vinall

Canakinumab is a human monoclonal antibody that
binds to the pro-inflammatory cytokine IL-1β and lowers

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