Cardiovascular Journal of Africa: Vol 30 No 1 (January/February 2019)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 1, January/February 2019

AFRICA

Myocardial Infarction in Scandinavia (TASTE) and Trial of

Routine Aspiration Thrombectomy with PCI versus PCI alone

in Patients with STEMI (TOTAL), which both failed to show

substantial clinical and perfusion benefit in patients despite

successful aspiration of clotting material.

9-11

Coronary thrombus material triggers thrombotic,

inflammatory, vasoconstrictor and other pathways, and

evacuating a portion of the thrombus and plaque material

addresses only a part of the pathophysiological problem.

Pharmacologically disrupting thrombus formation may be more

effective. Abciximab, a potent inhibitor of platelet aggregation,

disrupts fresh thrombus at high local drug concentrations, such

as those delivered by IC administration, and also exhibits anti-

inflammatory effects by inhibiting smooth muscle cell migration

and proliferation, thereby suppressing platelets, white blood cells

and endothelial-mediated mechanisms.

Adjunctive abciximab administration has been demonstrated

to reduce the rate of mortality and re-infarction in patients

with STEMI referred for invasive management.

The standard

abciximab regimen consists of an IV bolus followed by a 12-hour

IV infusion. Intracoronary administration has been suggested to

optimise myocardial perfusion beyond recanalisation, since anti-

glycoprotein IIb/IIIa concentration has been reported as much

as 280-fold higher with local compared with IV delivery.

Initial studies, in which abciximab bolus was delivered through

the guiding catheter after wiring the infarct-related artery, were

followed by the use of new application systems such as infusion

catheters. These systems consist of a perfusion balloon that

occludes anterograde blood flow while drugs are infused through

a microporous surface, thereby allowing achievement of high

drug concentrations and prolonged focal dwelling times at the

site of coronary thrombus. Delivery of abciximab through such

dedicated catheters (ClearWay Rx, Atrium Medical Hudson,

New Hampshire) was associated with a significant reduction in

thrombotic burden, improved microcirculatory flow, and lower

rates of one-year adverse events, compared with conventional

intracoronary drug administration through the guiding catheter

in the small, randomised COCTAIL-II trial.

Also, a meta-analysis of eight randomised trials to assess

the clinical efficacy and safety of intracoronary versus IV

abciximab in STEMI patients undergoing primary PCI showed

that intracoronary administration was associated with significant

benefits in myocardial perfusion, but not in clinical outcome at

short-term follow up.

Another meta-analysis of 14 randomised trials of IC versus

IV glycoprotein IIb/IIIa inhibitors with a total of 3 740 patients

undergoing primary PCI showed no statistically significant

difference between the IC and the IV groups for the primary

outcome of MACE. Subgroup analysis showed however that

the IC group was superior to the IV group in short-term MACE

rate, TIMI 3 flow, MBG 2 to 3 rates, improvement of LVEF, and

ST-segment resolution, compared to the IV group, with a trend

towards less stent thrombosis.

Among diabetic patients, IC versus IV abciximab bolus was

associated with a significantly reduced risk of death and stent

thrombosis and increased myocardial salvage.

16,17

In addition,

in the INFUSE-AMI study, randomisation to intralesional

abciximab through a ClearWay Rx catheter resulted in a modest

but statistically significant reduction in infarct size compared

with aspiration thrombectomy, but not with IV abciximab

administration. However, in this trial, there was no control group

of patients receiving IV abciximab.

Uncertainties regarding the use of IC abciximab are due, in

part, to mixed results observed across studies. Indeed, although

initial, small-sized investigations found an improvement in

surrogate endpoints with IC abciximab, the AIDA STEMI

trial, which was powered to assess clinical outcomes, failed to

demonstrate a reduction in the primary endpoint of all-cause

mortality, recurrent infarction, or new incidence of congestive

heart failure among patients randomised to IC compared to IV

abciximab bolus.

In the study by Piccolo

et al

. in diabetic patients, aspiration

thrombectomy was performed in fewer than 20% of patients,

while IC abciximab resulted in significant improvement of the

effectiveness of PCI, including an increased myocardial salvage

index and a reduced risk of death (5.8 vs 11.2%,

0.043).

The effectiveness of IC abciximab administration is also

supported by the Intracoronary Abciximab Infusion and

Aspiration Thrombectomy in Patients Undergoing Percutaneous

Coronary Intervention for Anterior ST-segment Elevation

Myocardial Infarction (INFUSE-AMI) trial, in which an IC

bolus of the glycoprotein IIb/IIIa inhibitor abciximab was

effective in reducing the infarct size, whereas thrombectomy by

means of manual aspiration was not.

In the INFUSE-AMI

trial, which did not include an IV abciximab administration

control group, the beneficial effects of intralesional abciximab

and thrombus aspiration were not additional. Nonetheless,

although debated, the question of potential benefits of IC

abciximab has recently been re-opened.

28-30

A recent meta-analysis of 14 trials of IC versus IV glycoprotein

IIb/IIIa inhibitors in patients with STEMI undergoing primary

PCI also showed improved ST-segment resolution rates and

superior angiographic results with IC glycoprotein IIb/IIIa

inhibitors, evidenced by improved achievement of post-procedural

TIMI 3 flow and MBG 2 to 3, compared with the IV group.

Overall, these observations suggest that adjuvant therapy

with aspiration thrombectomy or IC abciximab administration,

even in combination, are not required in all patients undergoing

PCI. They should rather be considered for selected patients only,

including those at increased risk of microvascular obstruction,

such as diabetics and patients with a large thrombotic burden or

severe distal coronary embolisation.

11,15,17,28-30

Trials to evaluate the

effectiveness of such approaches in these selected patients remain

to be undertaken.

Study limitation

A major limitation pertains to the selection of patients. Patients

with STEMI were included for primary PCI after a rather long

delay from symptom onset to catheterisation laboratory of about

300 minutes. This was due to the specific area where the study was

carried out, namely northern Africa. However, similar symptom-

to-door and symptom-to-balloon times have been reported in

registries from Egypt,

Tunisia

and Morocco.

Despite this

delay, primary PCI was performed instead of thrombolysis in

our study, as it was done in about 35% of patients included

in northern African registries.

25,31-33

We acknowledge that this

delay is not optimal to assess the efficacy of an IC delivery of

abciximab, an approach expected to improve distal perfusion

after recanalisation of the occluded coronary artery. Therefore