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over three quarters of patients had two or three
additional grafts). No significant differences
in major cardiovascular outcomes were
found over 5 years of follow-up. However,
the incidence of sternal wound complication
and reconstruction was 2 and 3-fold higher,
respectively, with bilateral IMA bypass
grafting, and all of these events occurred in
the first year and mainly in diabetics and those
with high BMI.
Of further note, 14% of patients assigned to
bilateral IMA underwent single IMA only
versus 2.4% of patients assigned to single
IMA undergoing bilateral IMA bypass surgery.
In summary, adding one more IMA graft
to patients undergoing CABG with LIMA
grafting does not add further clinical benefit
but may increase the risk of sternal wound
complication especially in at risk populations.
The PRECISION trial
This mega trial involved nearly 1000 centres
worldwide that enrolled 24,000 osteoathritis
or RA patients with CV disease or risk
requiring NSAID therapy for at least 6
months. Patients were randomly assigned to
celecoxib 100 mg bid, ibuprofen 600 mg tid,
or naproxen 375 mg bid in conjunction with
esomeprazole. Celecoxib was not inferior
to naproxen and ibuprofen with regards to
major adverse cardiovascular events in the
intention-to-treat analyses. In fact, in the
on treatment analyses it was associated
with a lower risk of cardiovascular events
and mortality compared with ibuprofen.
Celecoxib was associated with a lower risk
of major GI events compared with both
naproxen and ibuprofen and a lower risk
of serious renal events than ibuprofen and
even naproxen in the on-treatment analyses.
In the post-hoc analyses of any CV, GI, or
renal event, celecoxib had the lowest risk,
naproxen had intermediate risk and ibuprofen
the highest risk. These findings are striking as
they grant absolution to a drug condemned in
the cardiovascular community.
These charges date back to COX-2 inhibitor
story, which made headlines just over a
decade ago, pointing out the increased risk of
cardiovascular events with these drugs. Vioxx
was the prime contender and eventually left
the market in 2004; Bextra followed in 2005.
This has left Celebrex as the sole COX-2
inhibitor on the US market with stern black
box warnings. Other NSAIDs have also
been confronted with heightened levels of
concern eg, ibuprofen, whereas Naproxen has
prevailed in current opinion as one of the safer
representatives in his class. PRECISION
would attest that it is safer than ibuprofen,
but even so, the winner is, this time: celecoxib,
but against NSAIDS that also carry a risk.
The PIONEER AF-PCI Trial
The management of anticoagulation
and antiplatelet therapy in patients with
nonvalvular atrial fibrillation undergoing
PCI with stent implantation presents a
daily challenge, which was addressed in the
PIONEER AF-PCI trial (Gibson CM et al.
PIONEERAF-PCI. Paper presented at AHA
2016; November 12–16, 2016; New Orleans,
USA). This trial randomised 2100 of such
patients to one of three arms: rivaroxaban
15 mg once daily + thienopyridine x 12
months, rivaroxaban 2.5 mg twice daily +
DAPT x 1, 6, or 12 months (remainder to
12-month aspirin 75–100 mg once daily),
or warfarin (INR, 2–3) + DAPT x 1, 6, or
12 months (remainder to 12-month aspirin
75–100 mg once daily). Compared with the
last – the standard approach, known as triple
therapy – the two other novel anticoagulant
(NOAC) approaches were associated with
a 40% reduction in TIMI bleeding events
(primary endpoint) at no increased risk of
death, MI, or stroke (secondary endpoint)
and, on post hoc analysis (which needs to be
considered as hypothesis-generating), an even
25% reduction in the risk of hospitalisation
(related to both a CV and bleeding event).
While the first trial with NOACs with
important findings, one has to point out
that the dose of rivaroxaban was
lower than is commonly used. In
fact, this reduced dosing was never
tested and tried in atrial fibrillation
stroke prevention trials. Thus, it is not
surprising that it would lead to lower
bleeding events; and how effective
would it be for stroke prevention?
No true comparison was made with
the WOEST trial combination of
warfarin and clopidogrel (
Lancet
2013;381:1107–1115), a combination
which fared better than triple therapy
in that particular trial and in this
trial. There was no difference with
regard to the duration of 1, 6, or
12 months of DAPT; but, as not a
randomised comparison, these data
are also to be taken with a grain of
salt. As the duration was only for 1
year, the question of how to continue
thereafter is another, final one.
Thus, there is more to be explored, or,
speaking in terms of the investigators,
to be pioneered. Clinicians, however,
are provided now for some first-time
and much needed data on the use of
NOACs for the large and challeng-
ing population of atrial fibrillation
patients undergoing PCI.
DECEMBER 2016
AHA 2016
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