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Acute myocardial infarction (AMI) remains a major cause of morbidity
and the single most common cause of mortality among adult
Australians.1 It has been estimated that
there is one AMI every half hour and one fatal event every hour among men
and women under 70 years of age.1 Despite a decade of
remarkable insights into the pathobiology of AMI and innumerable
randomised clinical trials evaluating therapeutic approaches, the
optimal acute management strategy still remains unclear.
It is widely accepted that the primary objective in AMI is early
reperfusion,2 which, by preserving
myocardial cell viability and contractility, results in improved
survival.3-6 However, the main
mechanism of achieving coronary artery reperfusion -- intravenous
thrombolytic therapy -- is not without its limitations: up to half the
patients may be ineligible on clinical grounds, and it is only
moderately effective in reinstituting the level of coronary flow
necessary for improved survival.7 Other problems include
recurrent ischaemia, reinfarction and a small but significant
chance of life-threatening haemorrhagic
complications.8
Because of these drawbacks, interest in mechanical reperfusion by
primary coronary balloon angioplasty (without prior thrombolysis)
has steadily increased. Despite its 17-year history, balloon
angioplasty is not as widely available or as frequently
used9
as perhaps it should be (for reasons beyond the scope of this
editorial). However, current evidence for its use in primary
treatment of AMI is quite encouraging. A review of 10 randomised
clinical trials comparing primary coronary balloon angioplasty
with thrombolytic therapy in 2606 patients with AMI found those
treated with balloon angioplasty had a 34% lower mortality rate, a
lower rate of death and/or non-fatal reinfarction and a
significantly lower rate of total and haemorrhagic
stroke.10
Other randomised trials have indicated that, by
reducing early and late recurrent ischaemia, primary balloon
angioplasty may expedite early discharge and thus reduce
costs.11,12
Promising as these data might be, they are far from conclusive, in part
because of the size of the dataset and the unblinded nature of the
clinical trials. Almost 13 000 patients would need to be enrolled in a
trial to detect a 20% advantage in 30-day mortality rates of primary
coronary balloon angioplasty over thrombolytic therapy (assuming a
7% mortality rate in the thrombolytic therapy group).13 Equally
concerning are the incidence of no reflow due to distal thrombus
embolisation at the time of balloon dilatation; early recurrent
ischaemia and/or reinfarction (5%-10% of patients14) due to
elastic vascular recoil and/or platelet and thrombus deposition at
the site of balloon-induced intimal disruption (dissection); and
late restenosis (30%-50% of patients14) due to a varying mix of
neointimal proliferation, unopposed recoil and vascular
remodelling.
While there have been substantial improvements in operator skills,
procedural techniques, equipment design and adjunctive
antiplatelet therapies, the issues mentioned above continue to
frustrate the proponents of primary coronary balloon angioplasty.
It is not surprising, therefore, that they should have become
infected and intoxicated by the euphoria surrounding coronary
stenting in elective angioplasty. Compared with simple balloon
angioplasty, coronary stenting in elective (non-infarct-related)
coronary angioplasty has been shown to reduce the rate of
periprocedural complications and late restenosis, and to be
beneficial in the management of saphenous vein graft lesions and
restenotic lesions after balloon angioplasty.
The thought of in-situ coronary thrombus and the likely consequences
of deploying a metal stent into such an environment in a patient with
AMI initially struck fear into the hearts of even the most ardent
supporters of primary balloon angioplasty. However, the
realisation that antiplatelet therapy could prevent stent-related
thrombotic complications and the publication of a bold study of
primary infarct stenting without conventional anticoagulation
therapy15 strengthened the
advocates' resolve. This first study, although small and
non-randomised, paved the way for larger feasibility
trials,16 and, more recently,
randomised controlled trials of primary stenting in AMI.17,18 These
studies demonstrate a substantially lower rate of recurrent
ischaemia, reinfarction, angiographic restenosis and a reduced
need for target-vessel revascularisation compared with good old
balloon angioplasty. Unfortunately, neither of the randomised
trials had sufficient power to assess effects on mortality.
As is often the case with provocative new data, these observations on
primary stenting in AMI provide many more questions than answers.
Clearly, it is now important to establish in whom and by whom primary
stenting should be done. What patient, vessel or lesion
characteristics respond best to primary stenting? For example,
should primary stenting be the treatment of choice in diabetic
patients, who tend to have more diffuse atherosclerotic disease and a
higher risk of restenosis? Should only experienced operators
attempt primary stenting in AMI? Coronary stenting may add to the
complexity and risks of the procedure rather than lessen them, and
most of the recently published data16-18 emanate from centres
with unparalleled resources and expertise. Furthermore, what if the
lesion is not amenable to primary stenting, or, for that matter, even
primary angioplasty? The question of a second-line strategy is often
not addressed.
In this issue of the Journal, Hansen and colleagues19 indeed address some of
these important practical issues. In a pilot study, they assessed the
feasibility, safety and short term clinical outcomes of a primary
stenting strategy (embracing several critical contingency plans)
in a consecutive group of patients with AMI and eligible for
fibrinolysis. The authors observed that primary stenting was
possible in 71% of their cohort, and, by adopting a strategy that
included the "fall-back" options of simple balloon angioplasty,
emergency or semiurgent coronary artery bypass grafting (CABG) and
medical therapy, they achieved successful early revascularisation
of the infarct-related artery in 95% of their patients, with a
remarkably low rate of early, six-week and six-month cardiovascular
events.
The immediate questions that come to mind concern, firstly, the
costs, and what well-timed thrombolytic therapy might have achieved
in this cohort, and, secondly, whether these results can be
extrapolated to centres where resources such as CABG might not be as
readily available. The study by Hansen et al is limited by being
non-randomised and observational and the experience of a single
centre. Nonetheless, it provides important local insight into
primary stenting in AMI and indicates that this strategy is safe and
feasible and can be delivered in a timely fashion in an appropriately
equipped Australian hospital. Whether this holds true for patients
at remote centres is unknown, and it is not clear whether patients
should be denied early lytic therapy at one institution so they may be
transferred to another to obtain primary coronary balloon
angioplasty/primary stenting. Thrombolytic therapy has an
inherent time delay of approximately 45-60 minutes. A modest delay in
obtaining primary angioplasty/primary stenting may
therefore be acceptable, but has not been formally tested.
In summary, there is a growing body of evidence which suggests that
primary stenting in AMI may be preferable to primary coronary balloon
angioplasty and possibly more efficacious than conventional
thrombolytic therapies. However, no matter how enticing the data may
be, all the answers are not in. Does it save lives? Is it cost effective?
Is it widely applicable? Does it improve myocardial salvage? Are all
stents equal or are some more equal than others? Is it better than
primary coronary balloon angioplasty with adjunctive glycoprotein
IIb/IIIa platelet receptor blockade? These are but a few of the
questions that need addressing, and until these issues are resolved
primary stenting must be viewed as a procedure undertaken with the
best of intentions. And need I mention where the road paved with good
intentions might lead?
Ian T Meredith
Associate Professor; and Director, Cardiac Catheterisation and
Interventional Cardiology, Centre for Heart and Chest Research
Monash Medical Centre, Melbourne, VIC
Email: ian.meredithATmed.monash.edu.au
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©MJA 1999
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