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(Circulation. 1997;96:2762-2764.)
© 1997 American Heart Association, Inc.
Articles |
Keeping the Open Artery Open
Is Stenting the Answer?
From the Section of Interventional Cardiology, Beth Israel-Deaconess Medical Center, Boston, Mass.
Correspondence to Joseph P. Carrozza, Jr, MD, Section of Interventional Cardiology, Beth Israel-Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215.
Key Words: Editorials • stents • restenosis
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Introduction |
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 Top Introduction References |
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In the past decade, studies of thrombolytic therapy have established definitively that early patency of the infarct-related vessel is associated with improved left ventricular performance as well as enhanced in-hospital and long-term survival.1 2 Importantly, these reductions in early (30-day) and long-term (5-year) mortality are highly correlated with the restoration of normal (TIMI grade 3) versus TIMI grade 2 flow or less at discharge.3 4 Although thrombolytic regimens achieve arterial "patency" in almost 90% of patients, they restore TIMI grade 3 flow by 90 minutes in only
50% of
patients. Another limitation of thrombolytic therapy is that 10% of patients in whom successful reperfusion is obtained initially experience reocclusion before hospital discharge, and in 30%, the infarct-related artery reoccludes within 1 year.5 Although reocclusion is often clinically silent, it tends to negate the benefits of early reperfusion and is associated with poorer left ventricular function and higher long-term mortality. Taken together, these studies support what has been called the "open-artery" paradigm and further suggest that rapid reestablishment and maintenance of TIMI grade 3 blood flow are essential to achieving the best long-term outcome.
Our understanding of what role balloon angioplasty should play in treating the culprit vessel in acute myocardial infarction has evolved substantially over the past decade. Because acute coronary thrombosis usually occurs at the site of a ruptured atherosclerotic plaque, it seems intuitively obvious that balloon dilatation immediately after thrombolysis should reduce the underlying residual stenosis and thus improve coronary blood flow and clinical outcome. Unfortunately, the TIMI-2 trial showed that although patients treated with routine immediate or deferred (24 to 48 hours) percutaneous transluminal coronary angioplasty (PTCA) strategies had a lower residual stenosis, there was no benefit in 1-year mortality, reinfarction, or ejection fraction compared with a conservative (ischemia-driven) strategy in which only the minority of patients received angioplasty for clear clinical indications after intravenous thrombolytic therapy.6 Furthermore, PTCA immediately after thrombolysis appeared to be associated with higher incidence of emergency bypass surgery and hemorrhagic complications, possibly because of plaque instability and enhanced platelet activation that occurs with present-generation thrombolytic agents.
It was not clear, however, whether the failure of TIMI and other
studies to demonstrate a significant benefit for routine early
intervention after coronary thrombolysis also
applied to purely mechanical reperfusion (ie, primary PTCA) that was
used in lieu of (rather than after) thrombolysis.
Although small series in the late 1980s had suggested that primary
angioplasty was safe,7 only the 1994 publication of the
Primary Angioplasty in Acute Myocardial Infarction (PAMI) and similar
randomized trials demonstrated that primary dilatation of the
infarct-related artery may be equivalent or even superior to
thrombolytic therapy as a means to salvage
myocardium. In PAMI, direct PTCA reduced subsequent
mortality and reinfarction by up to 50% compared with
thrombolytic therapy, especially in high-risk
patients.8 9 Even subsequent trials such as GUSTO IIb, in
which "time to PTCA" was longer and the percentage of patients in
whom TIMI 3 flow was restored was lower, still showed substantial
(20%) reduction in mortality compared with
thrombolysis and supported the importance of quality of
the mechanical intervention measured by its ability to restore normal
(TIMI 3) flow.10 Although the benefits of primary
angioplasty compared with thrombolytic therapy in PAMI
are maintained to 6 months, the earlier Primary Angioplasty Registry
(PAR) and other data suggest that the ability to preserve an open
vessel with TIMI 3 flow is also essential to a favorable outcome. The
12% of patients with reocclusion and the additional 9% of patients
who had reduced (<TIMI grade 3) flow in PAR11 showed no
improvement in left ventricular ejection fraction compared
with the 8% absolute improvement in patients with persistent TIMI 3
flow. Other studies have documented that angioplasty performed after
thrombolysis is associated with a high incidence of
restenosis (51%) and reocclusion (13%), which correlates with
late reduction in left ventricular
function.12
Taken together, this growing body of data drawn from trials of both thrombolytic agents and primary angioplasty underscores the importance of rapid, complete, and durable restoration of normal blood flow in the infarct-related artery beyond merely "getting the artery open." Because trials in a number of other clinical situations have demonstrated that stenting (specifically Palmaz-Schatz stenting) provides enhanced early and late patency compared with balloon angioplasty, there has thus been growing interest in establishing whether stenting of the infarct-related artery in acute myocardial infarction would also provide similar benefits or whether the results would be compromised by an increased incidence of occlusive thrombosis. In the present issue of Circulation, the study by Bauters and colleagues, in which angiographic outcomes in patients whose infarct-related arteries were treated by stenting are compared with those in patients treated by conventional balloon angioplasty, is of major interest.13 The majority (60%) of patients had received thrombolytic therapy, with a median of 13 days from infarction to intervention (range, 24 hours to 30 days). This was thus a clinically heterogeneous population of patients containing a mixture of primary, rescue, delayed, and elective intervention. Although baseline angiographic variables were similar in the stenting and angioplasty groups, lumen diameter after the procedure was larger and the residual stenosis lower (10% versus 31%; P<.0001) in vessels treated by stenting. At 6-month follow-up, the incidence of angiographic restenosis was almost 50% lower (27% versus 52%; P<.005) in patients who received stents. In that study, stenting resulted in greater acute gain and a larger posttreatment lumen diameter than balloon angioplasty, and the observed restenosis rate of 27% was similar to that reported for elective stenting in the Benestent trial.14 The authors found that lower posttreatment diameter stenosis was independently associated with freedom from restenosis, in accord with observations from trials of elective stenting that "bigger is better" for reducing restenosis.15
Although the magnitude of benefit in reduction of restenosis
was impressive, the most startling finding in this study was the
reduction in reocclusion from 14% to 1% in the cohort treated by
stenting. The incidence of reocclusion within the first year after
peri-infarction balloon angioplasty is thus twofold higher than the
6% incidence of late reocclusion observed after angioplasty in
other noninfarction settings.16 In addition to mitigating
restenosis, the large, stable lumen provided by stenting may
have also reduced reocclusion due to in situ thrombosis, elastic
recoil, vasomotor tone at the site of dilatation, and poor distal
runoff caused by ischemic microvascular damage. This is
consistent with previous studies by these authors showing that
a small lumen diameter after conventional balloon angioplasty of an
infarct-related artery is associated with increased risk for
reocclusion. In contrast to the earlier view that placement of a stent
into a thrombotic milieu would increase the risk of stent thrombosis,
these data from Bauters further suggest that even a potentially
prothrombotic device (when optimally deployed to maximize luminal
cross-sectional area and vessel rheology) may actually reduce the
likelihood of thrombotic reocclusion.
Should one conclude that stenting ought to replace conventional balloon angioplasty as the mechanical treatment of choice for all culprit vessels in the peri-infarct period? Although the two cohorts appeared to be well matched in the present study, treatments were not assigned randomly, and selection bias for other factors may have influenced the outcome. Second, one cannot ignore the systematic confounder that 99% of stent patients were treated with the antiplatelet agent ticlopidine, compared with only 1% of the angioplasty patients. Part of the marked reduction in reocclusion in the stent patients may thus have been due to the antiplatelet effects of ticlopidine. Support for this concept comes from a small subset of the EPIC trial, in which patients treated with the platelet glycoprotein IIb/IIIa receptor blocker abciximab had a significantly lower cumulative incidence of repeat (early and late) revascularization by 6 months.17 Thus, balloon angioplasty performed in conjunction with potent antiplatelet therapy needs to be investigated as a potentially cost-saving alternative to stenting. Larger, prospective, randomized trials will certainly be needed to demonstrate that primary and peri-infarction stenting of the infarct-related artery translates into improved clinical outcome compared with balloon angioplasty and not just more appealing "luminal cosmetology."
Nonetheless, the data in aggregate strongly suggest that the open-artery paradigm is expanding: it is no longer sufficient to merely get the artery open but to also restore normal perfusion and to also maintain that normal flow during the critical first year after infarction. As the wave of "stentmania" expands into pivotal trials performed in the acute-infarction setting, one of the most important benefits of acute stenting may lie not only in maximizing acute infarct-related vessel patency but also in "keeping the open artery open."
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionReferences |
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2.
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4.
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