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Mechanical reperfusion therapy for acute myocardial infarction: Stent PAMI, ADMIRAL, CADILLAC and beyond
  1. B R Brodie,
  2. T D Stuckey
  1. Greensboro, North Carolina, USA
  1. Correspondence to:
    Dr BR Brodie, 313 Meadowbrook Terrace, Greensboro, NC 27408-6529, USA
    cvresearch{at}aol.com

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Mechanical reperfusion has gained increasing acceptance as a reperfusion strategy for acute myocardial infarction

Mechanical reperfusion has gained increas ing acceptance as a reperfusion strategy for acute myocardial infarction (AMI) as a result of data from numerous randomised trials showing superior outcomes. Recently, the Stent PAMI, ADMIRAL, and CADILLAC trials have documented further improvement in outcomes with the addition of adjunctive treatment with coronary stents and platelet glycoprotein IIb/IIIa inhibitors.1–3 Grines and colleagues, in the Stent PAMI trial, found that stents reduced target vessel revascularisation (TVR) and major adverse cardiac events (MACE) at six months compared to balloon angioplasty alone.1 (The Stent PAMI trial initially raised some concerns because the incidence of TIMI 3 flow was slightly lower following stenting versus balloon angioplasty, and there was a disturbing trend toward higher mortality in stented patients at six months. These concerns were resolved in the CADILLAC trial). Montalescot and colleagues, in the ADMIRAL trial, found that the use of the platelet glycoprotein IIb/IIIa inhibitor abciximab given before stenting in patients with AMI improved outcomes, resulting in better TIMI flow immediately following stenting and at six months, better recovery of left ventricular function at six months, and lower MACE at 30 days and six months.2

Stone and colleagues, in the recently completed CADILLAC trial, evaluated the combined role of stents and abciximab and documented the lowest event rates of any AMI trial to date (30 day mortality 2.0%, reinfarcation 0.7%, ischaemic TVR 3.3%, and disabling stroke 0.2%).3 CADILLAC, like Stent PAMI, found that stents reduced six month TVR and MACE, but unlike Stent PAMI, found no degradation of TIMI flow and no worse (slightly better) survival in patients treated with new generation stents compared to balloon angioplasty alone. CADILLAC, like ADMIRAL, found that abciximab was associated with fewer ischaemic events and lower 30 day MACE, although the benefit was seen mostly in non-stented patients and the benefit was not as pronounced as in the ADMIRAL trial, which enrolled a higher risk patient population and gave abciximab before percutaneous coronary intervention (PCI).

The primary objective of reperfusion treatment for AMI for nearly two decades has been the achievement and maintenance of brisk coronary flow in infarct artery. Mechanical reperfusion combined with adjunctive treatment with stents and platelet glycoprotein IIb/IIIa inhibitors has achieved this objective, with TIMI 3 flow rates of > 90–95%, reinfarction rates of < 1%, and late infarct artery reocclusion rates of < 5%. However, despite achieving very high rates of coronary reperfusion, recent data using sensitive markers of myocardial reperfusion, such as contrast echocardiography, myocardial blush assessment with angiography, and electrocardiographic ST segment resolution, indicate that about 50% of patients who achieve TIMI 3 coronary flow fail to achieve optimal myocardial reperfusion, and these patients have increased complications and worse outcomes.4 The reasons for suboptimal myocardial reperfusion are not fully understood, but likely include distal embolisation of platelet-rich microthrombi as well as microcirculatory dysfunction.

ADJUNCTIVE MEASURES

Adjunctive measures to improve myocardial reperfusion have included both pharmacologic and mechanical strategies. Pharmacologic strategies have been directed primarily at platelet glycoprotein IIb/IIIa inhibition with the expectation that dissolution of the platelet-rich microthrombi in the diseased epicardial segment will reduce obstruction in the distal microvasculature. Neumann and colleagues evaluated patients undergoing stenting for AMI and demonstrated that both peak flow velocity in the infarct related artery and regional wall motion index in the infarct zone were significantly improved at two weeks in abciximab treated patients compared to controls.5 Similarly, the ADMIRAL and CADILLAC trials both showed clinical benefit with abciximab, although only the ADMIRAL trial showed improved left ventricular function at six months.

There are several mechanical strategies under evaluation which may enhance myocardial reperfusion. The X-sizer thrombectomy catheter (EndiCOR Medical, San Clemente, California, USA) is designed for selective removal of thrombus and atheromatous debris before stenting. Cox and colleagues recently reported results using the X-sizer catheter before stenting in patients with AMI and found improved tissue perfusion compared to historical controls as measured by angiographic myocardial blush scores.6 Randomised trials are planned in an attempt to validate these findings. The Guardwire System (Percusurge Inc, Sunnyvale, California, USA) employs a balloon inflated in the coronary artery distal to the target lesion before PCI to prevent distal embolisation. The atheromatous and thrombotic debris captured proximal to the balloon are removed with aspiration following stent deployment. The SAFER trial, presented by Baim and colleagues at the Transcatheter Cardiovascular Therapeutics Scientific Sessions in Washington DC last year, documented a significant reduction in embolisation and periprocedural infarction using the Guardwire with elective saphenous vein graft intervention. The potential for benefit in AMI is substantial, but placement of the Guardwire in an occluded artery with no distal visualisation remains problematic. The Filterwire (Boston Scientific/EPI, Santa Clara, California, USA) employs a filter mounted on a self expanding nitinol ring which is deployed in the coronary artery distal to the target lesion before PCI. Atheromatous and thrombotic debris are captured in the filter at the time of stent deployment, after which the filter is removed. This device has the potential to prevent distal embolisation and enhance tissue reperfusion, but is yet to be studied in AMI. Other novel devices employing thrombectomy or distal protection are in the planning stages of clinical trials.

FACILITATED PCI

A major limitation of mechanical reperfusion is lack of immediate availability. This lack of availability and the realisation that an optimum reperfusion strategy will need to incorporate mechanical reperfusion as part of that strategy has led to a great deal of interest in pharmacologic reperfusion combined with mechanical reperfusion or facilitated PCI. Facilitated PCI is the use of pharmacologic reperfusion to establish TIMI 3 flow as rapidly as possible followed by immediate PCI to maximise TIMI 3 flow and to stabilise the ruptured plaque. Previous studies had found that PCI following thrombolytic treatment was not beneficial and potentially harmful, but more recent experience using coronary stents and platelet glycoprotein IIb/IIIa inhibitors have found that PCI can be performed safely and effectively after pharmacologic reperfusion treatment. The SPEED trial found that PCI following thrombolytic treatment or half dose thrombolytic treatment combined with platelet glycoprotein IIb/IIIa inhibitors was associated with superior outcomes compared to pharmacologic reperfusion treatment alone.7 The PAMI investigators and the Moses Cone Hospital Registry documented that patients undergoing primary PCI for AMI who arrive at the catheterisation laboratory with an open versus a closed infarct artery have higher procedural success rates, smaller infarct size, better recovery of left ventricular function, and lower early and late mortality.8, 9 These studies raise hope that facilitated PCI may improve outcomes over primary PCI alone, and this hypothesis will be tested in the FINESSE trial. This approach would be ideal for patients presenting at hospitals without interventional facilities to allow time for transfer for mechanical intervention.

Although there is much enthusiasm for facilitated PCI, a word of caution is needed. The major objective of facilitated PCI is to reduce the time delay inherent with mechanical reperfusion, but time to reperfusion appears to be less important with primary PCI than with thrombolytic treatment.10 Also, combination pharmacologic treatment using half dose thrombolytics and platelet glycoprotein IIb/IIIa inhibitors, which is being tested in facilitated PCI trials, has an increased bleeding risk and the same finite risk of intracranial haemorrhage as standard thrombolytic treatment as documented in the recent GUSTO V trial.11 Whether the benefit of facilitated PCI will be sufficient to outweigh these risks and to justify the increased costs is uncertain.

The past two decades have witnessed gradually improving outcomes with reperfusion treatment for AMI, beginning with first generation thrombolytics, followed by second and third generation thrombolytics combined with aspirin, heparin, and now platelet glycoprotein IIb/IIIa inhibitors, and most recently with mechanical reperfusion combined with stents and platelet glycoprotein IIb/IIIa inhibitors. New frontiers with reperfusion therapy will focus on improving reperfusion at the level of the microcirculation and combining pharmacologic with mechanical reperfusion to expand the benefits of mechanical reperfusion to a much broader patient population. This synergy between pharmacologic treatment and a variety of novel mechanical approaches holds promise to further improve outcomes with reperfusion treatment for AMI.

Mechanical reperfusion has gained increasing acceptance as a reperfusion strategy for acute myocardial infarction

REFERENCES

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