ESC Focus on Interventions & PC - 8

Late-Breaking Clinical Trials

Rivaroxaban Plus Aspirin Superior
to Aspirin Alone in Patients With
Stable Cardiovascular Disease:
Results From the COMPASS Trial
Written by Maria Vinall

8

October 2017

Significantly more major bleeding occurred in the
2 rivaroxaban arms compared with aspirin alone. The
rivaroxaban 2.5 mg plus aspirin arm increased major
bleeding by 70% (3.1% vs 1.9%; HR, 1.70; 95% CI, 1.40 to
2.05; P < .001) while major bleeding in the rivaroxabanalone arm was increased by 51% (HR, 1.51; 95% CI, 1.25
to 1.84; 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 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; HR, 1.50;
P = .03 for rivaroxaban 5 mg).
With respect to the 7,470 patients with PAD, Sonia
Anand, MD, McMaster University, Hamilton, Ontario,
Canada, reported that the combination of rivaroxaban
Figure 1. Primary Composite 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

Cumulative Hazard Rate

Primary results from the COMPASS trial [Eikelboom JW et
al. N Engl J Med. 2017] presented by John W. Eikelboom,
MD, McMaster University, Hamilton, Ontario, Canada,
showed that rivaroxaban plus aspirin improves outcomes
in patients with stable cardiovascular (CV) disease.
COMPASS was a multicentre, randomised, prospective, double-blind, 3-arm superiority trial. Patients (27,395)
from 602 centres in 33 countries were randomised
(1:1:1) to 2.5 mg BID rivaroxaban plus 100 mg QD aspirin,
or 5 mg BID rivaroxaban alone, or 100 mg QD aspirin
alone. The primary study endpoint was a composite of CV
death, stroke, or myocardial infarction (MI). Safety and
net clinical benefit was derived from a modified ISTH
major bleeding score and included fatal bleeding, symptomatic bleeding into a critical organ, bleeding into a
surgical site requiring reoperation, and bleeding that
led to hospitalisation.
At baseline, 91% of participants had a history of coronary artery disease and 27% a history of peripheral
artery disease (PAD). There was high use of evidencebased therapies: 90% of patients were on lipid-lowering agents; 71% on an angiotensin-converting enzyme
inhibitor or angiotensin-receptor blocker; and 70% on
β-blockers. Participants (22% women) were a mean age
of 68 years with a mean blood pressure of 136/78 mm Hg
and mean total cholesterol of 4.2 mmol/L. The Data and
Safety Monitoring Board recommended discontinuation
of the rivaroxaban/aspirin arms of the study for clear
benefit of rivaroxaban.
There was a significant 24% reduction in the primary
endpoint among participants randomised to combination therapy compared with aspirin alone (HR, 0.76;
95% CI, 0.66 to 0.86; P < .001); rivaroxaban alone was
not significantly better than aspirin alone (HR, 0.90;
95% CI, 0.79 to 1.03; P = .12; Figure 1). For the individual
components of the primary endpoint, the reduction was
significant in the combination-therapy group for CV
death (RRR 22%; P = .02) and stroke (RRR 42%; P < .001)
but not for MI (RRR 14%; P = .14).

0.08
0.06
0.04
Aspirin
Rivaroxaban
Rivaroxaban + aspirin

0.02
0.0
0

1

Years

2

3

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.

medicom-publishers.com/mcr
http://www.medicom-publishers.com/mcr
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