Background Arterial atherosclerosis can affect any organ in the body, and its consequences are devastating and potentially life threatening. Myocardial infarction (MI), stroke and peripheral vascular disease (PVD) are all commonplace throughout both the developed and developing worlds. Advances both in pharmacotherapy and angioplasty techniques have meant that a fair proportion of this disease burden can be dealt with by percutaneous and nonsurgical options. Coronary angioplasty is an established way of dealing with simple and increasingly complex coronary disease. Carotid and renal stenting are also gaining favor as the preferred treatment options compared to either medical therapy or surgical treatment. As the use of vascular stenting increases, so the drive to reduce potential complications and improve success rates intensifies. Initially, in smaller caliber vessels, especially with coronary stenting, the main limitation of success was the risk of restenosis. This issue has largely been overcome in the era of drug-eluting stents (DES). As interventionalists take on more challenging cases, the focus has shifted towards improving not only epicardial, but also microvascular flow by preventing downstream embolization from the angioplasty site. Such distal embolization can occur with any vascular intervention. Although embolization from local atheroma has long been recognized as a potential complication in vascular surgery, direct evidence of this phenomenon was also observed during saphenous vein graft (SVG) angioplasty. There is now increasing evidence that similar embolization also occurs during carotid and renal stenting, and in certain native coronary lesions with a high thrombus burden. Innovative new techniques are being pioneered to improve the success rates of endovascular stenting and one of the areas on which clinical emphasis is focused is that of embolic protection. In this article, we review areas of vascular intervention where distal protection is being used, the types of protection devices available, examine the evidence for their use and discuss future concerns and directions. Carotid stenting. Carotid endarterectomy (CEA) is a well-recognized and effective treatment for stroke prevention in patients with significant carotid stenosis.1 The standard of care for both symptomatic and asymptomatic carotid artery stenosis has been established by the results of a number of large, prospective randomized trials of medical therapy and CEA namely The North American Symptomatic Carotid Endarterectomy Trial (NASCET),2 the MRC European Carotid Surgery Trial (ECST)2 and the Asymptomatic Carotid Atherosclerosis Study (ACAS).3 These studies demonstrated a significant reduction in ipsilateral stroke at five years with CEA compared to conservative treatment in patients with symptomatic carotid stenosis > 50% or asymptomatic stenosis > 70%. Carotid artery stenting (CAS) as an alternative to CEA has always been viewed with caution. Carotid atherosclerotic lesions are similar histologically to coronary lesions with a lipid rich core and an overlying fibrous cap.5 The carotid plaque is often friable and the concern with stenting has justifiably, always been the high risk of distal embolization with its potential catastrophic risk of stroke. Studies using transcranial Doppler have demonstrated evidence of distal embolization in every patient treated.6 Advances in techniques and equipment have, however, made carotid stenting a viable alternative to endarterectomy. To date, there has only been one completed prospective multicenter trial comparing endovascular with surgical treatment: the Carotid And Vertebral Transluminal Angioplasty Study (CAVATAS).7 This study reported similar outcomes with CAS and CEA, despite the fact that most of the CAS patients were treated with balloon angioplasty alone, and 10,11 and a large retrospective review of registry data demonstrated that embolic protection significantly reduced the rate of stroke and thromboembolic complications (1.6 versus 5.5%, p 12 The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)13 study was the first randomized trial of CEA versus CAS with distal protection, using the Angioguard (Cordis Endovascular, Miami Lakes, Florida) filter. More than half the patients who were screened were considered too high risk for CEA and underwent CAS as part of a high-risk, non-randomized registry. Stenting markedly reduced the primary composite endpoint of death, stroke, or acute myocardial infarction (AMI) at 30 days and death or ipsilateral stroke at one year compared to the surgical group (12.2 versus 20.1%, p = .004). The reduction in primary endpoint was driven predominantly by a reduction in AMI at 30 days. However, the peri-procedural complication rates in both study arms were relatively high and the outcomes in the CEA groups were much worse than for NASCET or the other major trials of CEA and this may have led to an overestimation of the benefit of CAS. Despite shortcomings, such as the inclusion of a substantial numbers of patients with restenosis in whom the risk of repeat surgery would have been higher and the risk of embolization lower, this trial has been pivotal in establishing the equivalence of carotid stenting (with embolic protection) to endarterectomy in high-risk patients. The US FDA has subsequently approved carotid stenting for use in high-risk patients with either symptomatic or asymptomatic carotid stenosis. The results of SAPPHIRE were strengthened by the subsequently published ACCULINK for Revascularization of Carotids in High-Risk Patients (ARCHeR) studies,14 a sequential series of three prospective, nonrandomized, multicenter studies in which 580 high surgical risk patients underwent carotid stenting with the ACCULINK (Guidant, Indianapolis, Indiana) nitinol stent, using the ACCUNET (Guidant) filter embolic protection in the last two series. The primary composite endpoint of 30 day death/stroke/MI plus ipsilateral stroke at 1 year was 9.6%, significantly lower than the 14.4% historical endarterectomy controls, demonstrating that the results of carotid stenting with filter protection were not inferior to historical results of endarterectomy. These results were also borne out by the recent Stent Protected Angioplasty versus Carotid Endarterectomy in symptomatic patients (SPACE) trial,15 which also demonstrated that carotid stenting is not inferior to the historical risks of CEA among high-risk surgical patients. In this study of some 1000 patients, they were randomly assigned to carotid stenting or endarterectomy. However, embolic protection was used only at the operator’s discretion (27% of patients). In the non-adjusted comparison of patients treated with and without a device, no significant difference in the periprocedural complication rate was noted, but this study was not powered to examine this specifically. The recently published CREATE registry reported on the use of an over-the-wire embolic protection filter, the SPIDER (ev3, Plymouth, Massachusetts) system. It concluded that percutaneous revascularization with distal protection is a safe and reasonable alternative to CEA in patients with severe carotid stenosis who are at high risk for CEA. There was a suggestion however that longer procedure times and particularly, longer filter deployment times may be associated with a higher risk of complications. In patients with filter deployment duration greater than 20 minutes, the risk of death and stroke was almost double that of patients with shorter filter deployment times. It is difficult to ascertain whether shorter procedures represent more simple intervention or operator skill and familiarity with equipment. The level of operator expertise in carotid stenting was also cited as a potential factor in the results demonstrated in the recently published EVA-3s trial.17 This study of endarterectomy versus stenting in patients with symptomatic severe carotid stenosis was prematurely stopped due to the higher risk of stroke or death after carotid stenting at six months (6.1% versus 11.7%). However, in this study, initially cerebral protection was not used, and when it did become incorporated in the study design, five different stents and seven different cerebral protection devices were used. Although cerebral protection devices were used in 92% of stenting procedures, concerns remain regarding the quality of embolic protection in this study. The requirement for operator experience with only 2 embolic protection procedures prior to use of a new protection device and the number of devices used raises significant concerns about the possibility of poor operator skill with such cerebral protection device use. These concerns have been highlighted by published guidelines that emphasize operator competency and standards.18 Definitive conclusions condemning stenting on the basis of this trial are, in our opinion, premature. Comparatively, the results from SAPPHIRE appear more promising, possibly related to the fact that only one type of filter device was used. The debate continues over CAS versus CEA as the optimal treatment of these patients, with several ongoing trials including Carotid Revascularisation Endarterectomy versus Stenting (CREST) trial19 and CAVATAS 2,20 which will evaluate stenting with embolic protection in lower risk patients. Several different types of embolic protection devices have been evaluated in carotid stenting, including the GuardWire (Medtronic AVE, Santa Rosa, California), ACCUNET,21 FilterWire (Boston Scientific, Santa Clara, California), and the Emboshield (Abbott Vascular Devices, Abbott Park, Illinois). Although reduced, peri-procedural strokes have not been entirely eliminated by the use of first generation embolic protection systems. These were deployed distal to the lesion, possibly allowing embolization to occur before protection was in place. The use of the newer proximal protection devices may thus reduce stroke risk further. Although the published series so far only pertain to small patient numbers, use of the Parodi Anti-Embolic System (Arteria, San Francisco, California)25 and the Mo.Ma proximal occlusion system (Invatec, Brescia, Italy)26 appear to be very favorable. Saphenous vein graft intervention. Distal protection devices have been studied most extensively in the setting of coronary intervention, in particular in saphenous vein graft (SVG) intervention. The problem of SVG plaque embolization was first described more than 15 years ago.27 Embolization manifests as a visible reduction in epicardial flow and results in variable degrees of downstream myocardial necrosis. SVG plaques are distinct from those in native vessels, with histological characteristics that make them more susceptible to embolization. Such plaques are soft and friable, being lipid-rich with little calcium content. Prior to the routine use of embolic protection, the risk of a major adverse event or no-reflow phenomenon with SVG intervention was very high, up to 20% in some series28 and largely attributable to procedure-related distal embolization of atheromatous debris. The Saphenous vein graft Angioplasty Free of Emboli Randomized trial (SAFER) randomized 800 patients to conventional SVG stenting or stenting with the GuardWire distal protection device.29 Embolic protection achieved an absolute 6.9% reduction in 30-day death, AMI, emergency CABG, and target vessel revascularization. This study was pivotal in establishing not only that distal protection was useful in collecting debris and reducing the phenomenon of no-reflow, but its use also conferred a significant mortality and morbidity benefit. Consequently, the use of embolic protection has become standard practice in SVG intervention. The FilterWire, CardioShield (Abbott Vascular Devices) and TriActiv (Kensey Nash, Exton, Pennsylvania) system have all been evaluated and appear to show favorable results.30 The 2005 ACC/AHA/SCAI guideline update for percutaneous coronary intervention (PCI) recommends that distal embolic protection devices be used, if technically feasible, in patients with SVG disease. Native coronary artery disease. Native coronary artery intervention carries a much lower risk of distal embolization compared with vein graft intervention.31,32 In patients with stable angina, the risk of embolization is relatively small and therefore embolic protection systems have not been evaluated and are not used in uncomplicated native vessel PCI. However, in patients with acute coronary syndromes (in particular those with ST-elevation), who often have a relatively high thrombus burden overlying the unstable plaque, the risk of downstream embolization of thrombus during intervention is appreciable. However, there are no data to suggest that the routine use of embolic protection is beneficial in all comers with acute coronary syndrome undergoing PCI. One possible explanation for this may be that, in contrast to the cholesterol emboli released during SVG intervention, such thrombotic platelet emboli may be spontaneously lysed in the distal myocardial bed without causing clinical sequelae, obviating the need for embolic protection. Of all cardiac patients, the highest intraluminal thrombus burden is encountered in those with AMI undergoing emergent (primary or rescue) angioplasty. The Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris (EMERALD) trial randomized 500 such patients to angioplasty with a distal occlusion balloon (GuardWire) or conventional angioplasty.32 Even in this high-risk population, there was no difference between the groups in terms of ST-segment resolution at 30 minutes, final infarct size or in the incidence of 6-month major adverse cardiac events (MACE). This lack of benefit was confirmed in the PROMISE trial33 of 200 patients undergoing primary PCI in which use of an adjunctive filter device was evaluated (FilterWire EX). Why the devices failed to offer a significant benefit is unclear, but there are a number of possibilities (see discussion). Renal artery stenting. Renal artery disease is both a common disease in patients with atherosclerosis and also a relatively uncommon cause of secondary hypertension. Renal artery stenosis (RAS) may cause chronic renal failure if it affects both renal arteries or if the hypertension associated with this condition is prolonged or severe. Atherosclerotic renovascular disease is present in approximately 7% of the general elderly population34 and in up to 40% of individuals with coronary or PVD.35 Renal insufficiency is also a recognized risk factor for cardiovascular mortality and morbidity. Fibromuscular thickening of the renal arterial wall is a rarer, congenital cause of RAS in younger adults, particularly women aged 20–40 years. Once RAS has been established as a cause of hypertension, there are three treatment options available; namely medical, renal angioplasty or surgery. The ACC/AHA guidelines suggest that patients with unilateral RAS should have their hypertension controlled with medication.36 Revascularization is recommended in those patients with resistant or malignant hypertension, hypertension with an otherwise unexplained small kidney, those intolerant to anti-hypertensive medication or those with recurrent episodes of “flash” pulmonary edema. A number of carefully conducted controlled trials have compared surgical treatment with a medical approach and also stenting with balloon angioplasty. One multicenter study in which patients with RAS and resistant hypertension were assigned to either medical therapy or balloon angioplasty showed no difference in medication requirements or renal function at one year.37 However by 3 months, 44% of patients assigned to drug therapy had required rescue angioplasty because of refractory hypertension. These findings are supported by a meta-analysis, which showed that balloon angioplasty was significantly more effective at lowering blood pressure than medical therapy, although there appears to be no difference between the two treatments with respect to preserving renal function.38 Akin to the direction in other vascular interventions, there has been an increasing trend towards the elective use of stenting in renal angioplasty. However, there is very little in the way of randomized controlled data to support this practice. A number of non-controlled studies in atherosclerotic ostial lesions, which are more prone to restenosis, have demonstrated improvement or stabilization of renal function and improved blood pressure control,39,40 and a lower rate of restenosis with stenting.41 A recent meta-analysis of 14 studies involving some 700 patients undergoing RAS revealed a high technical success rate, with hypertension cured in 20% and improved in 49% of patients.42 Renal function improved in 30% and stabilized in 38%. Although the evidence favors stenting with respect to its benefit on renal function, it adds relatively little to the benefit already achieved with balloon angioplasty. The ACC/AHA guidelines suggest that stenting should be performed when revascularization is undertaken especially in patients with ostial atherosclerotic disease.36 Renal angioplasty and stenting are now increasingly performed43 and open surgical revascularization is now rarely used. As with all revascularization procedures, there have been concerns raised regarding the possible deleterious effects of procedure-related athero-embolization, particularly the effect on renal function. The lack of improvement in renal insufficiency with renal artery stenting in some studies,44,45 or even deterioration in renal function, is generally attributed to procedure-related contrast nephropathy, distal embolization or a progression of renal disease. Embolic debris in renal intervention mainly consists of cholesterol emboli released from the renal lesion and also from the atheromatous aorta. Distal embolization has been shown to cause parenchymal loss and deterioration in renal function both acutely and in the weeks after the procedure.46 Without undertaking specific renal scans however, the effect of procedural embolization is reflected only very crudely in the overall deterioration of renal function and may well be underestimated. The recent ASPIRE-2 study reported that embolic events occurred in 6.3% of renal stenting procedures.47 Importantly, in-hospital clinically-evident athero-embolization occurred in only 1.4% of cases; and these were not associated with an increase in post-stent serum creatinine values or with mortality. Distal embolic protection devices have been used in renal stenting but their use is sporadic, depending on the center and the operator. There is very little prospective randomized data available. Two studies using distal protection have demonstrated that embolic material is retrieved in all cases using the GuardWire occlusion device and in 80% of cases when using the FilterWire or Angioguard.48,49 These studies demonstrated improvement in renal function in 40% cases and no acute deterioration was seen. These excellent results, which are superior to earlier reports in the literature, presumably reflect the benefit of a reduction in peri-procedural athero-embolization. Unanswered questions about the efficacy of stenting with embolic protection are being addressed by the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial,50 a randomized multicenter trial comparing RAS using distal protection with medical therapy in more than 1000 patients. Lower extremity peripheral intervention. As with all other vascular disease the treatment options for lower extremity peripheral arterial disease include medical, surgical and percutaneous options. When considering chronic disease, the AHA guidelines36 recommend endovascular intervention for type A (single stenosis less than 3 cm) iliac and femoropopliteal arterial lesions. Surgical treatment is recommended for more complex disease. In patients with acute limb ischemia, catheter-based thrombolysis is generally accepted as the treatment of choice. There are also limited data on the use of thrombectomy devices in those patients in whom thrombolysis is contraindicated. Distal embolization has been recognized as a complication of peripheral intervention and embolization rates of 1.6–2.4% are reported in iliac and lower extremity intervention.51 As with coronary intervention, distal embolization during an acute occlusion is higher due to the increased thrombotic burden and published series in this subgroup suggest embolization rates of up to 37%, depending on risk.52 Embolic protection is not routinely used during percutaneous intervention and there have been no trials addressing the role of distal protection in this type of intervention. A few case series have been published, but the number of patients is very limited. A case series of 5 high-risk patients (patients with ischemic symptoms requiring either thrombolysis or mechanical thrombectomy) utilized both the filter and distal occlusion balloon.53 All five devices retrieved substantial debris. This study demonstrated that the use of embolic protection is feasible. The significance and implications of such protection, however, are still to be defined. Embolic Protection Devices Historical approaches to limit the problem of distal embolization in the setting of already established thrombus include the intra-arterial or intra-coronary administration of thrombolytic agents and direct thrombectomy. It is not within the scope of this review to focus on thrombectomy devices here, but they have been reviewed elsewhere.30 Embolic protection systems have a number of advantages over these earlier approaches, namely the absence of significant hemorrhagic risk and the ability to deploy the protection device prior to intervention even before a thrombus is formed or before emboli are liberated. There are currently a number of devices on the market, each being associated with varying degrees of success. Three basic approaches to embolic protection have been developed, namely 1) the arrest of flow by occluding the artery distal to the target lesion and aspiration of debris (distal occlusion systems); 2) filtration of the blood distal to the target lesion (filter devices); and 3) occlusion of the artery proximal to the lesion with aspiration (proximal occlusion systems). Distal occlusion devices. This system consists of a guidewire incorporating a central inflation lumen to which an inflation balloon is attached. Injection of diluted contrast results in balloon inflation arresting flow in the vessel. Intervention is performed over the wire, and liberated debris trapped proximal to the balloon is removed using an over-the-wire aspiration catheter. The balloon is then deflated and flow restored. The GuardWire (Figure 1) system was the prototype embolic protection system and has the biggest evidence base from clinical trials both in carotid54 and coronary29 angioplasty. The TriActiv system is a newer distal protection device which is under evaluation. The main disadvantages of such systems are firstly, as with filters, that in deploying the device distal to the lesion, embolization may occur before protection is in place; and secondly, total arrest of flow hinders visualization during angioplasty and may not be well-tolerated if supporting vessels do not provide a good collateral supply. Filter devices. The filter systems comprise a non-occlusive filter (of varying pore sizes) in the shape of a windsock, mounted on a nitinol loop. These are either fixed on the guidewire or ride over any commercially-available guidewire. They are deployed to beyond the target lesion through a delivery sheath. When the sheath is retracted, the nitinol loop self expands to fit the vessel, and intervention is performed over the wire. After intervention, the device is recaptured using a retrieval sheath. Protection devices in this group include the FilterWire (Figure 2), Spider (ev3, Plymouth) (Figure 3), Angioguard, Cardioshield/Neuroshield (Abbott) and the Rubicon (Rubicon Medical, Salt Lake City, Utah) filter. These devices have been evaluated in coronary55 and carotid angioplasty21,22 as well as some renal procedures.56 The advantage of filters is that they maintain antegrade flow and are also relatively easy to use. Their main disadvantages are that the filter pores may allow microemboli to pass through the filter unhindered and, furthermore, the device needs to traverse the lesion of interest before it can be deployed and this maneuver may dislodge emboli before protection is in place. However, a direct comparison of balloon occlusion systems with filter devices revealed no difference in efficacy outcomes.57 Proximal occlusion devices. The Proxis (Velocimed, Maple Grove, Minnesota) device incorporates a sealing balloon that is deployed upstream of the stenosis to create a stagnant column of blood in which intervention is performed (Figure 4). Thus, the main advantage of such a system is that protection is in place before any device crosses the lesion. Following intervention, liberated debris is aspirated, and the sealing balloon is then deflated, restoring flow. Initial experience with this system in coronary intervention is promising,58 although preliminary data from the PROXIMAL Embolic Protection trial presented at TCT 2005 suggested that the 30-day MACE rate was no lower with the Proxis device than with using distal protection. Most experience with proximal occlusion systems has been obtained in carotid intervention, with the Mo.Ma26 and the Parodi Antiembolic Systems.25 Occlusion balloons are deployed in the external carotid and the common carotid artery. This results in retrograde blood flow down the internal carotid artery, a flow direction that prevents embolization to the brain during stent insertion. The main disadvantages of proximal occlusion devices are that (as with distal occlusion systems) visualization of the stenosis is lost during arrested flow and there is a risk of cerebral ischemia during prolonged flow reversal without a sufficiently developed supporting collateral circulation. Each of the devices has its own advantages and disadvantages and no device is lesion specific. A “landing zone” is essential to safely and effectively deploying the embolic protection system, and for this reason, proximal protection devices are clearly not suitable for ostial or very proximal lesions, while filters and distal balloon systems need a suitable vessel run-off beyond the lesion to be deployed. Other important considerations include the potential tolerability by the target organ of the arrest of antegrade flow, as well as technical considerations for successful deployment such as vessel tortuosity and embolic protection system profile. Discussion Table 1 summarizes the overall current evidence and recommendations for the use of embolic protection in percutaneous intervention. Carotid angioplasty. Based primarily on the SAPPHIRE data, guidelines issued in 2006 by the American Heart Association/American Stroke Association (AHA/ASA) recommend that carotid stenting be considered for patients with symptomatic severe (> 70%) carotid stenosis who have difficult surgical access to the stenosis, medical conditions that greatly increase the risk of surgery, or other specific circumstances such as radiation-induced stenosis or restenosis after CEA.59 The benefit of embolic protection in this setting was easier to establish than in other target organs, possibly because it has been easier to quantify the extent of embolization with the use of transcranial Doppler. Unfortunately, the clinical sequelae of embolization can also be as evident as they are devastating. Although there are more defined guidelines, areas of concern still remain. Firstly, there is a distinct paucity of data from prospective controlled trials on the efficacy of embolic protection devices in patients undergoing carotid stenting. There are also problems noted with the use of embolic protection systems, such as the phenomenon of “slow flow”, which occurs in the internal carotid artery proximal to the filter devices, and is thought to be caused by the occlusion of the filter membrane pores by microemboli and debris.60 On the basis of the data published so far, the use of carotid stenting, even with distal protection, cannot be recommended routinely. Its role lies mainly in high-risk surgical patients who are unable to undergo endarterectomy. However, given the overall magnitude of benefit seen with embolic protection and stenting in the SAPPHIRE trial, it is debatable whether carotid stenting without embolic protection will ever be ethical. For the time being, if CAS is performed, it should be done with embolic protection in place. Coronary angioplasty. The role of embolic protection devices is well established in SVG intervention, but there are few data regarding their merit in native coronary arteries. This is likely to reflect the differing nature of the embolic material in vein grafts, which comprises lipid and necrotic atheroma core, rather than the thrombotic emboli in native vessels. Furthermore, the differing endpoints used in the different trials have compounded the problem. Although vein graft studies have predominantly shown a benefit on the “hard” clinical endpoint of 30-day MACE, studies in native vessels have failed to show a benefit even on much “softer” surrogate endpoints, such as ST-segment resolution. While embolic protection should be used if technically possible in SVG intervention, for the time being, embolic protection should not be routinely used in native coronary intervention. Renal angioplasty. The data for renal stenting are also not straightforward to interpret; but generally, simple lesions should be treated with angioplasty and stent insertion, mainly to achieve an antihypertensive effect and also to potentially improve renal function. However, it is difficult to ignore some evidence of deterioration in renal function after stent placement. Although this may be related to procedure-related athero-embolization, other possible contributors include contrast nephropathy. The recent ASPIRE 2 trial47 indicates that the rate of clinical distal embolization during renal angioplasty is small, but paradoxically for a trial with such a low rate of embolization, this trial failed to show any improvement in renal function in response to stenting, suggesting perhaps that distal embolization was underestimated. Data on the use of embolic protection in this patient population are predominantly observational and from case series. A randomized controlled trial comparing RAS with and without embolic protection is lacking. The ongoing CORAL study comparing protected RAS (with distal protection) with medical therapy should hopefully resolve some of these issues. However, even if this supports the use of embolic protection, the choice of device remains undefined. Future Directions and Complementary Approaches More sensitive identification of embolization and consistency in endpoints. In native coronary artery studies, almost every embolic protection study has used a different surrogate endpoint to indicate the extent of embolization. The crudest indicator of embolization is the phenomenon of no-reflow, which is defined as thrombolysis in myocardial infarction (TIMI) ?2 flow in the absence of macrovascular obstruction.61,62 It reflects distal embolization caused by PCI, resulting in microcirculation damage63 and is associated with an adverse prognosis.64 Various other methods have been used to indirectly assess the extent of myocardial damage from distal embolization. In clinical trials, the commonly used measures are angiographic indicators of myocardial flow, namely TIMI frame count and myocardial perfusion grade, and more recently flow velocity and pressure measurements. Other measures include the rise in myonecrotic enzymes, namely cardiac troponin T, troponin I or CKMB, ECG changes, perfusion assessments via contrast echocardiography and contrast-enhanced cardiovascular magnetic resonance and Single photon emission computed tomography (SPECT). A recent review article comparing these techniques concluded that SPECT sestamibi imaging is currently the best available technique for the quantification of infarct size.65 Unfortunately, the vast majority of trials are guilty of using suboptimal measures of no-reflow or myocardial enzyme rise, and hence the true benefit of embolic protection in native vessels may well be underappreciated. Better patient and/or target lesion selection. While there are still areas of doubt regarding the exact role of embolic protection, it may be that a case-tailored approach is required. Use of embolic protection inevitably increases the cost and length of the procedure. Therefore, it may be most useful and cost effective to identify patients who are at greatest risk of peri-procedural atheroembolism. For example, with renal angioplasty, this would include the elderly, patients with renal failure, those with diseased aorta and those with bilateral RAS or a solitary functioning kidney. Identifying plaques at greatest risk of athero-embolization during intervention is another promising avenue and recent work on plaque morphology indicates that identification of the unstable plaque may be helpful in delivering a tailored approach. In a retrospective study in which angioscopy was performed in AMI patients undergoing primary PCI with or without distal protection, ruptured plaque was identified in 55% patients.66 No-reflow was most common in patients with a ruptured plaque treated without distal protection and furthermore, clinical benefit from distal protection was only seen in patients with ruptured plaque. Other angioscopic studies have suggested that it is yellowish plaques with an increased lipid core and thin fibrous cap that are associated with a higher incidence of acute ischemic events, rather than white plaques which have higher fibrin content.67 This highlights the need to identify the vulnerable plaque, at least in the native coronary circulation. As plaque rupture is often the precipitating event in acute coronary syndromes, it is reasonable to hypothesize that a similar process may occur with carotid disease. In one report of endarterectomy specimens from 19 symptomatic and 25 asymptomatic patients, plaque rupture was significantly more common in patients with symptoms.68 It is likely that inflammation is also important in carotid plaques. With the use of FDG-PET scanning, inflammation can be visualized non-invasively in carotid plaques, and the degree of inflammation is significantly greater in symptomatic plaques.69 The possible clinical application of FDG-PET or the intravascular technique of Virtual HistologyTM (Volcano Therapeutics, California) to target intervention with embolic protection to high-risk plaques remains to be defined. Plaque modification. Although the focus of this review has been the reduction of distal embolization with mechanical devices, it is important not to forget the role of pharmacotherapy in reducing the risk of embolization. Statins in particular have been shown to stabilize atherosclerotic plaques and those that are vulnerable to rupture.70 Intracoronary ultrasound has demonstrated reduced progression of mean plaque volume or thickness and increased plaque hyperechogenicity with atorvastatin compared to placebo,71 indicating a change in plaque composition from lipid-rich to fibrotic and calcified that corresponds to increased plaque stability and a reduced tendency for rupture.