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Two treatment
strategies of
rivaroxaban reduce
rehospitalisation
in patients with
AF undergoing
intracoronary stenting
In patients with atrial fibrillation who underwent
intracoronary stenting, two rivaroxaban strategies
reduced rehospitalisations potentially attributable
to either bleeding or cardiovascular events.
T
his outcome of a study comparing rivaroxaban plus a
P2Y12 inhibitor monotherapy or rivaroxaban plus dual
antiplatelet therapy was reported at the AHA Scientific
Sessions 2016.
Michael Gibson, MS, MD, of Beth Israel Deaconess Medical
Center, Boston, Massachusetts, explained that patients
with atrial fibrillation who undergo intracoronary stenting
traditionally are treated with a vitamin K antagonist plus dual
antiplatelet therapy, though this treatment leads to high risk
of bleeding.
Dr Gibson and colleagues hypothesised that a regimen of
rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban
plus dual antiplatelet therapy would reduce bleeding and exert
a favourable impact on all-cause mortality and the need for
rehospitalisation.
Stented subjects with nonvalvular atrial fibrillation (n=2124)
were randomised 1:1:1 to:
•
Group 1:
reduced-dose rivaroxaban 15 mg daily plus a
P2Y12 inhibitor for 12 months.
•
Group 2:
rivaroxaban 2.5 mg twice daily with stratification
to a prespecified duration of dual antiplatelet therapy of 1,
6, or 12 months.
•
Group 3:
the reference arm of dose-adjusted vitamin K
antagonist daily with similar dual antiplatelet therapy
stratification.
Post hoc analysis assessed the endpoint of all-cause mortality
or recurrent hospitalisation for an adverse event, which was
further classified as the result of bleeding, a cardiovascular, or
another cause blinded to treatment assignment.
The risk of all-cause mortality or recurrent hospitalisation
was 34.9% in Group 1 (hazard ratio 0.79, 95% CI 0.66–0.94,
P = 0.008 vs Group 3, number needed to treat 15); 31.9% in
Group 2 (hazard ratio 0.75; 95% CI 0.62–0.90; P = 0.002 vs
Group 3, number needed to treat 10); and 41.9% in Group 3
(vitamin K antagonist + dual antiplatelet therapy).
Both all-cause death plus hospitalisation potentially resulting
from bleeding (Group 1, 8.6% [P = 0.032 vs Group 3]; Group 2,
8.0% [P = 0.012 vs Group 3]; and Group 3, 12.4%); and all-
cause death plus rehospitalisation potentially resulting from a
cardiovascular cause (Group 1, 21.4% [P = 0.001 vs Group 3],
Group 2, 21.7% [P = 0.011 vs Group 3]; and Group 3, 29.3%)
were reduced in the rivaroxaban arms vs the vitamin K antagonist
arm, but other forms of rehospitalisation were not.
Dr Gibson concluded that among patients with atrial
fibrillation undergoing intracoronary stenting, administration
of either rivaroxaban 15 mg daily plus P2Y12 inhibitor
monotherapy or 2.5 mg rivaroxaban twice daily plus dual
antiplatelet therapy was associated with a reduced risk of all-
cause mortality or recurrent hospitalisation for adverse events
vs standard-of-care vitamin K antagonism plus dual antiplatelet
therapy.
While ticagrelor was nomore effective in
reducing risk than clopidogrel, we learned
valuable information about this population,
specifically, that patients with a history
of lower extremity revascularisation are
at higher risk of acute limb events and
cardiovascular events.
>8
With the remarkable lipid lowering
enabled by the combination of statin
and anti-PCSK9 antibodies, wemay be
wringing asmuch “milk out of the stone”
as we can by lessening lipid accumulation
in the atheroma.
>8
In summary, adding onemore IMA graft
to patients undergoing CABGwith LIMA
grafting does not add further clinical
benefit but may increase the risk of
sternal wound complication especially in
at risk populations.
>9
Reconstituted apolipoprotein A-I CSL112
enhances cholesterol efflux after acute MI
The reconstituted, infusible, plasma-derived apolipoprotein A-I has been shown to enhance choles-
terol efflux after acute myocardial infarction, with no significant alterations in liver or kidney function
or other safety concern, reports the Apo-I Event Reducing in Ischemic Syndromes I (AEGIS-I) trial.
M
ichael Gibson, MS, MD,
of Beth Israel Deaconess
Medical Center, Boston,
assachusetts, explained that human
or recombinant apolipoprotein A-I has
been shown to increase high-density
lipoprotein – mediated cholesterol efflux
capacity and to regress atherosclerotic
disease in animal and clinical studies.
CSL112 is an infusible, plasma-derived
apolipoproteinA-I that has been studied
in normal subjects or those with stable
coronary artery disease.
AEGIS-I was a multicentre,
randomised, double-blind, placebo-
controlled, dose-ranging phase 2b trial.
Patients with myocardial infarction
were stratified by renal function and
randomised 1:1:1 to CSL112 (2 g
apolipoprotein A-I per dose) and high-
dose CSL112 (6 g apolipoprotein
A-I per dose), or placebo for four
consecutive weekly infusions.
Coprimary safety endpoints were
the occurrence of either a hepatic
safety event (an increase in alanine
transaminase more than three times the
upper limit of normal or an increase in
total bilirubin more than twice the upper
limit of normal) or a renal safety event (an
increase in serum creatinine >1.5 times
the baseline value or a new requirement
of renal replacement therapy).
A total of 1258 patients were
randomised, and 91.2% received
all four infusions. The difference in
incidence rates for an increase in
alanine transaminase or total bilirubin
between both CSL112 arms and
placebo was within the protocol-defined
noninferiority margin of 4%.
Similarly, the difference in incidence
rates of an increase in serum creatinine
or a new requirement for renal
replacement therapy was within the
protocol-defined noninferiority margin
of 5%. CSL112 was associated with
increases in apolipoprotein A-I and
ex vivo cholesterol efflux similar to
that achieved in patients with stable
coronary artery disease.
With regard to the secondary efficacy
endpoint, the risk for the composite of
major adverse cardiovascular events
among the groups was similar.
Dr Gibson concluded that among
patients with acute myocardial
infarction, four weekly infusions of
CSL112 were shown to be feasible, well
tolerated, and not associated with any
significant alterations in liver or kidney
function or other safety concern. The
ability of CSL112 to acutely enhance
cholesterol efflux was confirmed. The
potential benefit of CSL112 to reduce
major adverse cardiovascular events
needs to be assessed in an adequately
powered phase 3 trial.
AHA 2016
VOL. 1 • No. 3 • 2016
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