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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 3, May/June 2019
AFRICA
165
Discussion
For STEMI patients with an onset of symptoms of less than 12
hours, it has been clearly demonstrated that an early restoration
of the patency of the infarcted artery is critical to improve clinical
outcomes.
17
Current clinical practice, however, includes a high
proportion of patients with acute MI who present beyond this
time limit. In the present study, we found that 22.8% (729 of 3
202) of STEMI patients presented late (more than 12 hours) after
the symptom onset. Our results are similar to those of previous
reports
2-5,18
STEMI patients who present late would be outside of the
‘golden time window’ for reperfusion and are expected to exhibit
less myocardial salvage, an expansion of infarct size as well as
a higher mortality rate when compared with early comers.
7-10
Therefore, it is of great valuable to explore an optimal therapy
strategy for these patients, aiming to provide the best prognosis
as well as the lowest related risk. Patients who presented at 12 to
72 hours after the onset of symptoms were defined as ‘early late-
comers’.
5
In the last few years, much attention has been paid to
the controversy of whether these late-comers could benefit from
PCI.
13,14,19,20
Based on the different status of IRA patency, previous
studies have shown conflicting results.
13,20
The BRAVE-2
13
and Danish
14
trials were the two most valuable
studies concerning this issue. Data from BRAVE-2 showed that
primary PCI with adjunctive use of abciximab reduced infarct
size
13
and four-year mortality rate
21
in patients with acute STEMI
without persistent symptoms, presenting 12 to 48 hours after
symptom onset. The Danish study
14
showed that myocardial
salvage could still be achieved, even when primary angioplasty
was performed in STEMI patients beyond the 12-hour limit.
Because of this powerful clinical evidence, routine primary
PCI strategy was given a IIa recommendation for STEMI patients
who present 12 to 48 hours after symptom onset by both 2014
and 2017 editions of the European Society of Cardiology (ESC)
guidelines.
22,23
Two issues must however be noted in these trials.
First, in the Danish study, angioplasty in patients presenting 12
to 72 hours after symptom onset shared the same salvage index
(%) with patients who presented less than 12 hours after symptom
onset (81 vs 71%,
p
=
0.42). This indicated that in STEMI patients
who presented late and with a patent IRA, the time window in
which PCI could be beneficial may exceed the 48-hour limit up
to 72 hours or even later. Second, 43.4% (79 of 182) of patients
in the BRAVE-2 study and 43.6% (24 of 55) in the Danish study
who received primary PCI had a patent IRA, according to initial
angiographic results.
Previous studies have shown immediate PCI resulted in a
higher rate of procedural failure compared with delayed PCI in
patients who presented less than 12 hours after onset of symptoms
with a patent IRA.
16
Similar results were found in patients whose
MI had occurred more than 12 hours to less than seven days
earlier, and PCI before day 4 experienced a higher rate of failure,
24
but the status of IRA patency was not taken into consideration in
this study. Based on these results, we may speculate that if patients
had been treated differently according to their initial status of
IRA patency in the BRAVE-2 and Danish trials, the results may
have been even better than published.
It seems that patency of the IRA plays an important role and
patients with a patent IRA who present 48 to 72 hours post onset
of symptoms still benefit from PCI. What remains unclear is when
late reperfusion should be performed to provide the best clinical
results, as well as the lowest related risk. This has not been well
established since there are limited data available on this clinical
condition.
25
We hypothesised that delayed PCI could be better than an
emergency strategy among these patients. In our study, we found
that in STEMI patients who presented 12 to 72 hours after
symptom onset with IRA TIMI flow grades of 2 to 3, emergency
PCI had a lower rate of procedural success due to higher rates of
slow flow or no re-flow of IRA during the operation, compared
with the delayed PCI strategy, whereas in-hospital MACE and
mortality rates were similar in the two groups.
Several explanations may exist for our results. First, the
thrombus becomes organised and firmer as time progresses
during the acute phase of acute myocardial infarction (AMI).
26
The organised thrombus is broken down into fragmented debris
by mechanical devices such as balloons or stents during primary
or elective PCI, and this debris causes embolisation of the branch
or distal vessels and can completely plug the microvasculature,
resulting in the slow flow or no re-flow phenomenon. Second,
antithrombotic agents play an important role in preventing
generation and expansion of the thrombosis.
Many studies have shown than an antithrombotic agent creates
a safe environment for PCI by preventing re-occlusion.
27
In our
study, the use of dual antiplatelet therapy was common in both
groups, but only loading doses of aspirin and clopidogrel were
given before PCI in the emergency group, while the delayed PCI
group of patients were maintained for at least one day on a routine
dose of aspirin plus clopidogrel in addition to the loading dose.
Platelet activation may be incompletely suppressed if clopidogrel
is initiated only at the time of PCI.
28
Moreover the delayed PCI
group had a much higher rate of LMWH treatment compared
with the emergency PCI group (8.46 vs 100%,
p
<
0.001).
Sufficient duration of antithrombotic therapy maintained a stable
haemodynamic state, allowing the drugs to take effect, and gave
the lesion time to ‘cool off’.
29
Furthermore, although our study
showed that GPIIb/IIIa receptor antagonists were used more
frequently in the emergency group (24.3 vs 4.7%,
p
=
0.015), they
were primarily used only during the emergency PCI procedure,
and late initiation may limit antithrombotic function.
In this study, PCI of a significantly stenosed infarcted artery
was performed in all the late-coming STEMI patients enrolled.
Our practice was based on the following evidence. First, the
12-hour time limit in primary angioplasty is based on two facts:
(1) thrombolysis would not be efficacious in patients with AMI
beyond 12 hours from symptom onset;
18,30
(2) late presenters were
not included in the trials that showed the superiority of primary
angioplasty over fibrinolysis.
31,32
This indicates that the 12-hour
limit established for fibrinolysis may not be relevant in primary
angioplasty.
Second, human AMI has a stuttering course with intermittent
occlusion and re-canalisation. Previous studies showed the infarct-
related artery was not totally occluded in up to one-third of
patients.
18
Third, the attenuation of chest pain in patients with AMI
may result from necrosis-related sympathetic denervation and
does not necessarily reflect a decrease in myocardial ischaemia.
30
In this study, we found 115 late-coming AMI patients who were
asymptomatic but presented with a target lesion of 80 to 99% and
a median of 95% stenosis, according to initial angiography data. It
is clear that the lack of chest pain may not be used as an index to
rule out the necessity of mechanical reperfusion in these patients.