Compared with aspirin alone, a regi- men of rivaroxaban plus aspirin is
associated with better cardiovascular
outcomes among patients with stable
atherosclerotic vascular disease, according to research published August 27 in
the New England Journal of Medicine. Although the combination increases the risk
of major bleeding events, it has greater
net clinical benefit than aspirin alone, said
“Even small improvements in the effectiveness of treatments that prevent stroke and heart
attack are important, because cardiovascular disease is
very common,” said John W. Eikelboom, MBBS, Associate Professor of Hematology and Thromboembolism at McMaster University in Hamilton, Canada. The
treatment effect in the current study was “
unexpectedly large,” he added.
COMPASS: An International Trial
“Efforts to improve aspirin have focused primarily on
combining aspirin with another antiplatelet drug or
replacing aspirin with another antiplatelet drug, but
this [tactic] has had only limited success,” said Dr.
Eikelboom. He and his colleagues conducted the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, a double-blind study
to evaluate whether rivaroxaban, a selective direct factor Xa inhibitor, either alone or in combination with
aspirin, would be more effective than aspirin alone for
secondary cardiovascular prevention.
The study took place at 602 centers in 33 countries.
Eligible patients met the criteria for coronary artery
disease, peripheral arterial disease, or both. Among
the exclusion criteria were high bleeding risk, recent
stroke or previous hemorrhagic or lacunar stroke,
severe heart failure, and advanced stable kidney dis-
ease. During a run-in phase, participants received a
rivaroxaban-matched placebo twice daily
and aspirin (100 mg/day). Participants
who adhered to this regimen were ran-
domized in equal groups to rivaroxaban
( 2. 5 mg bid) plus aspirin (100 mg/day),
rivaroxaban ( 5 mg bid) plus placebo once
daily, or aspirin (100 mg/day) plus pla-
cebo twice daily.
The primary efficacy outcome was
the composite of cardiovascular death,
stroke, or myocardial infarction. The
main safety outcome was a modification
of the International Society on Thrombosis and Hemostasis criteria for major bleeding. The investigators
intended to continue the trial until at least 2,200 participants had a confirmed primary efficacy outcome.
They planned formal interim analyses of efficacy
for when 50% and 75% of primary efficacy events
Study Was Stopped Early for Efficacy
The investigators enrolled 27,395 participants into
the trial. The population’s mean age was 68.2, and
22.0% of participants were women. The mean systolic
blood pressure was 136 mm Hg, the mean diastolic
blood pressure was 78 mm Hg, and the mean total
cholesterol level was 4. 2 mmol/L. Having observed a
consistent difference in the primary efficacy outcome in favor of rivaroxaban plus aspirin, the independent data and safety monitoring
board recommended early termination of the study at
the first formal interim analysis for efficacy.
The rate of primary outcome events was 4.1% (379
patients) in the rivaroxaban-plus-aspirin group, 4.9%
(448 patients) in the rivaroxaban group, and 5.4%
(496 patients) in the aspirin group. Compared with
aspirin alone, rivaroxaban plus aspirin reduced the risk
of the primary outcome by 24%. Rivaroxaban alone
reduced the risk of the primary outcome by 10%,
Combination of Rivaroxaban and Aspirin
Improves Cardiovascular Outcomes
Although the combination increases the risk of major bleeding, its net clinical benefit
is greater than that of aspirin.
John W. Eikelboom, MBBS