The overall rate of "definite or probable" stent thrombosis within 30
days of PCI was about 1.4% in a prospectively planned substudy of the
Acute Catheterization and Urgent Intervention Triage Strategy
(ACUITY) trial, which randomized patients with "moderate- or high-
risk" ACS to early invasive management using one of several
antithrombotic regimens, report investigators in the February 10,
2009 issue of Circulation [1].

The early stent-thrombosis risk didn't significantly vary among the
different adjunctive regimens, which consisted of either heparin or
bivalirudin with glycoprotein (GP) IIb/IIIa inhibitors or bivalirudin
without GP IIb/IIIa inhibition. The risk was also unrelated to the
timing of GP-IIb/IIIa-inhibitor administration and to whether
patients received drug-eluting stents (DES), which were used in 90%
of cases, or only bare-metal stents.

Independently significant predictors of stent thrombosis at 30 days
included a lack of preprocedural thienopyridine treatment and reduced
in-stent minimum luminal diameter, according to the authors, led by
Dr Jiro Aoki (Columbia University Medical Center, New York, NY).
Unsurprisingly, poor compliance with postprocedure thienopyridine
therapy was also a risk factor for early stent thrombosis.

"It concerns me that, whether with drug-eluting stents or bare-metal
stents, the stent-thrombosis rates are still relatively high,"
regardless of antithrombin regimen, ACUITY primary investigator Dr
Gregg Stone (Columbia University Medical Center) commented to
heartwire. "So I think we need to, one, modify the risk factors we
can modify, which means pretreat with thienopyridines; two, emphasize
prolonged thienopyridine use as per guidelines, one year or longer of
dual antiplatelet therapy; and three, optimize the angiographic
result with appropriately sized balloons and/or pressure."

In ACS, some PCI operators like to get "in and out," Stone said. "But
to make a good job of stenting we really do need to try to optimize
the result and get as close to a zero percent residual stenosis as
possible, to try to minimize the risk of stent thrombosis. So I think
technique does matter."

Stent thrombosis is certainly worth avoiding; in the current ACUITY
30-day analysis, patients with definite or probable stent thrombosis
had increased rates of death, MI, unplanned revascularization, and
major bleeding.

The complication hasn't recently received the attention it deserves,
contend Drs Stéphane Cook and Stephan Windecker (Swiss Cardiovascular
Center, Bern) in an accompanying editorial [2]. It's been
overshadowed, they write, by the specter of late stent thrombosis
since the first controversial allegations in 2006--covered
extensively since then by heartwire--that it may be more likely after
DES than bare-metal-stent procedures.

The current ACUITY analysis, Cook and Windecker write, "will
reinforce our quest to strive for an optimal postprocedural result"
and "underscores the importance of timely and adequate inhibition of
platelet aggregation in patients with acute coronary syndromes
undergoing PCI." It suggests that supplementary GP IIb/IIIa
inhibition "be strongly considered in the absence of thienopyridine
treatment."

Agreeing, Dr Ron Waksman (Washington Hospital Center, Washington,
DC), who isn't an ACUITY coauthor, said the analysis emphasizes that
in the setting of invasive management of ACS, patients should be
preloaded with clopidogrel. But, he commented to
heartwire, "glycoprotein IIb/IIIa inhibition probably does have a
role in this setting, specifically when patients are not preloaded--
or even if they are preloaded on the table, when they have pills in
their stomach that aren't yet doing anything."

The ACUITY trial's primary outcomes were reported in 2006 [3]. As
covered by heartwire at the time, the trial randomized 13 819
patients invasively managed for ACS to receive one of the three
antithrombin regimens and saw a "noninferior" rate of a composite
ischemia end point--which included death by any cause--for the
bivalirudin regimens compared with heparin plus GP IIb/IIIa
inhibition.

The trial came with its own controversy; also as covered by
heartwire, some observers questioned ACUITY's statistical definition
of noninferiority, alleging that it favored outcomes in the
bivalirudin arms.

The current analysis focused on the trial's 3405 patients implanted
with at least one stent and evaluated by quantitative coronary
angiography according to a prospective protocol. The 30-day rate of
definite or probable stent thrombosis was 1.4% overall and 1.1% for
heparin plus GP IIb/IIIa inhibitors, 1.6% for bivalirudin with GP
IIb/IIIa inhibitors, 1.5% for bivalirudin alone, and 1.4% for both
DES and bare-metal-stent procedures (no significant differences).

The complication was associated with significantly increased rates of
death (27% vs 0.4% for no early stent thrombosis), MI (79% vs 6.7%),
and unplanned ischemia-driven PCI or CABG (67% vs 2.4%); all
differences were significant at p<0.0001.

The timing of clopidogrel initiation in ACUITY was at the operator's
discretion, Waksman observed, but its early-stent-thrombosis outcomes
underscore that preloading should be routine in ACS. In fact, he
said, the importance of thienopyridine preloading likely outweighs
the role of stent placement technique for cutting the early stent-
thrombosis risk.

"Clearly, if you get good [angiographic] results in patients with
unstable angina, you still have a higher risk of MI than in patients
with stable angina," Waksman said. "The more unstable the patient,
the more stent thrombosis. That's why [in ACS] you have to be more
meticulous with antiplatelet therapy."

The ACUITY trial was funded by the Medicines Co and Nycomed;
individual author disclosures are in the report. Windecker reports
consulting for and receiving lecture fees from Abbott, Biosensors,
Biotronik, Boston Scientific, Medtronic, and Johnson & Johnson.


Aoki J, Lansky AJ, Mehran R, et al. Early stent thrombosis in
patients with acute coronary syndromes treated with drug-eluting and
bare metal stents: the Acute Catheterization and Urgent Intervention
Triage Strategy trial. Circulation 2009; 119:687–698. Abstract
Cook S, Windecker S. Early stent thrombosis: past, present, and
future. Circulation 2009; 119:657–659. Abstract
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with
acute coronary syndromes. N Engl J Med 2006; 355:2203–2216.Abstract