Neuroendovascular Issues

Alim P. Mitha, Michael K. Tso, Felipe C. Albuquerque, Cameron G. McDougall, and John H. Wong

Manipulation of catheters, coils, balloons, and stents within the blood vessels makes the issue of coagulation most relevant to the endovascular neurosurgeon. The interventionalist must be constantly aware of the coagulation status of the patient to optimize patient management and to remain in neutral balance between the risk of thromboembolic and hemorrhagic complications. This, in turn, requires thorough knowledge of the mechanisms of platelet aggregation; of the numerous antithrombotic therapies available, including antiplatelet agents, anticoagulants, and fibrinolytic compounds; as well as the agents that reverse their effects.

This chapter reviews the basic issues and commonly used management paradigms used before, during, and after neuroendovascular procedures. Also addressed will be the coagulation issues related to specific techniques, including embolization, stenting, thrombolysis, as well as iatrogenic complications such as hemorrhage. Strategies for monitoring the coagulation status as well as the indications and methods of anticoagulation reversal postprocedure are also described here.

Issues related to the Use of Anticoagulants Before and During Endovascular Procedures

General Neuroendovascular Procedures: Angiography, Aneurysm Coiling, Embolization of Arteriovenous Malformation or of Tumor

The risk of thromboembolic complications associated with angiographic procedures makes the issue of anticoagulation particularly important. Diffusion-weighted imaging lesions after endovascular procedures have been reported to occur at rates as high as 69%, although most of these radiographic lesions are asymptomatic.1–3 Clinically evident permanent neurologic complications associated with diagnostic angiography are reported to occur in 0.5% of cases, and in 6 to 9% of neurointerventional procedures such as aneurysm coiling.⁴ The clinical incidence of stroke due to arteriovenous malformation (AVM) and tumor embolization is more likely related to the embolysate material penetrating blood vessels supplying normal tissue rather than to inadequate anticoagulation during the procedure.

For any angiographic procedure, it is generally desired that the prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) be normalized prior to puncture of the femoral artery. For patients on a continuous infusion of intravenous (IV) heparin, this implies that the infusion be stopped for 1 to 2 hours and that the PT be checked prior to the procedure. These measures will help to prevent groin-site complications such as retroperitoneal hemorrhage that may result from repeated arterial punctures due to potentially difficult femoral access. An alternative approach to those patients on intravenous heparin who are particularly prothrombotic includes continuing their medication while the groin puncture is performed, but to be prepared for immediate reversal with protamine if arterial access becomes complicated.

For those patients on warfarin, it is recommended that their INR be reversed prior to puncture, because hemorrhage complicating femoral artery access could persist for several hours before obtaining reversal with appropriate blood products or vitamin K. If anticoagulation cannot be safely reversed and there is no significant urgency to the procedure, then the INR should be allowed to drift downward spontaneously before carrying out angiography, or the patient can be bridged with heparin. If the procedure is being performed on an anticoagulated patient with an acute hemorrhage or for an urgent or emergent indication, then the INR should be actively reversed with blood products such as fresh frozen plasma (FFP), cryoprecipitate, or vitamin K.

Dabigatran is an oral direct thrombin inhibitor that is an alternative treatment to warfarin used in the prevention of stroke in patients with nonvalvular atrial fibrillation. This medication should be discontinued 1 to 2 days prior to nonurgent endovascular procedures. However, in acute clinical scenarios that require urgent reversal of anticoagulation, there is no antidote or reversal agent currently available for dabigatran. Administration of FFP or prothrombin complex concentrate (PCC) may attenuate the anticoagulation effects of dabigatran and should be given as a last resort. Because dabigatran is cleared via renal pathways, hemodialysis is an option to accelerate the elimination of dabigatran but is not a practical option in most cases. A normal PTT value in a patient taking dabigatran suggests that little anticoagulation activity is present.

Endovascular catheters and wires exposed to blood flow serve as a nidus for thrombus formation. Catheters are generally made from polyurethane, polyvinylchloride, or polyethylene, whereas wires can be made from stainless steel, nitinol, or platinum. A hydrophilic coating made from polytetrafluoroethylene (Teflon) is typically, but not always, present on microcatheters and guidewires. Catheters and wires with hydrophilic coatings generally reduce thrombogenicity compared with the nonhydrophilic types, but this also depends on the contrast agent being used and how catheters and devices are maintained during the procedures. Nearly all contrast agents reduce platelet aggregation, but this effect is more pronounced with ionic contrast agents. Nonionic contrast agents such as iodixanol and iopromide are thought to be more thrombogenic compared with ionic types.5 Aggressive cleaning of catheters and wires, continuous flushing of catheters with heparinized saline, preventing stasis of flow around tips of catheters, avoiding catheter-induced vasospasm, and systemic heparinization all help to reduce the chance of thrombus formation.

There is no consensus data on the use of intravenous heparinization during conventional angiographic procedures. Generally, if the procedure is short and uncomplicated, such as a diagnostic angiography, no intravenous heparinization is required. If the procedure evolves into one requiring catheter exchanges or requires a longer than normal amount of time (upward of 30 to 45 minutes), then intravenous heparinization should be considered at a dose of 70 to 100 units per kilogram, to an activated clotting time (ACT) goal of 250 to 300 seconds, or at least double the baseline value.

Alternatives to heparin exist for patients with documented heparin-induced thrombocytopenia including argatroban. Argatroban can be used in doses of 350 µg/kg bolus over 3 to 5 minutes or a continuous drip of 10 to 25 µg/kg/min. As with heparin, ACT values of 250 to 300 seconds should be targeted. Other alternatives include bivalirudin, lepirudin, and danaparoid.

For AVM or tumor embolization procedures that are anticipated to be short, one could consider not systemically heparinizing the patient, which may aid in the overall goal of thrombosis of the target vascular lesion. However, as a general rule, if catheter exchanges are anticipated, large-bore catheters (> 5 French) are to be used, or if the procedure is expected to be long, then systemic heparinization should be administered.

For ruptured intracranial aneurysms, we prefer to withhold anticoagulation until the first coil has been deployed within the aneurysm dome. At that point, we proceed with a full dose of intravenous heparin. However, the protocol for anticoagulation treatment in patients with ruptured aneurysms is controversial and some interventionists prefer to systemically heparinize the patient prior to any embolization, whereas others prefer to heparinize after the aneurysm has been well coiled.

Stents

Stenting procedures demand particular attention to the coagulation status of a patient because of the intent to introduce a therapeutic, but thrombogenic, foreign body permanently into the vascular system. Most of the experience with antiplatelet therapy in the setting of stent placement comes from cardiac procedures. Compared with coronary stents, however, intracranial stents are likely to be less thrombogenic because current versions used for carotid or intracranial atherosclerotic disease and aneurysm neck remodeling are self-expanding as opposed to the coronary balloon-expandable types. Self-expandable stents cause less mechanical stress to the underlying arterial surface, limiting the extent of endothelial injury and resulting in less thrombogenicity. Nevertheless, rates of thromboembolic complications with stent-assisted neuroendovascular procedures remain significant. The literature has reported stent-associated thromboembolic complication rates as high as 28%.5

In elective cases likely to involve the placement of a stent, such as for carotid or intracranial atherosclerotic disease or for aneurysm neck remodeling, an antiplatelet regimen must be initiated before the procedure. Acetylsalicylic acid (ASA) 325 mg daily and a 2-day loading dose of clopidogrel 300 mg daily, followed by 75 mg daily, both beginning at least 2 days prior to and including the morning of the procedure, is recommended. However, if a stent is required more urgently, a loading dose of ASA 650 mg and clopidogrel 600 mg can be administered the day prior to the procedure followed by ASA 325 mg and clopidogrel 75 mg on the morning of the procedure. Ideally, platelet inhibition should be confirmed before the procedure because up to 65% of patients are resistant to conventional doses of ASA and up to 30% of patients are resistant to clopidogrel.⁶

During the stenting procedure, intravenous heparinization should be performed to an ACT goal of 250 to 300 secondes, although some recommend reaching an ACT of 300 to 350 seconds because of the higher thromboembolic risk associated with these interventions.⁷ Following the placement of a stent, dual antiplatelet therapy with ASA 325 mg and clopidogrel 75 mg is recommended for a 6-week to 3-month period, followed by ASA 325 mg indefinitely thereafter. In the case of drug-eluting stents, such as those occasionally placed for large-vessel extracranial disease, a longer duration of dual antiplatelet therapy, typically 6 months to 1 year, is required because of the prolonged period necessary for endothelialization.

Stent placement is generally not recommended in the setting of acute intracranial hemorrhage. Nevertheless, situations may arise that demand deployment of a stent in a patient with acute bleeding, such as in the case of proximal atherosclerotic disease limiting endovascular access to a more distal target, arterial hemorrhagic dissection, or coil herniation from a ruptured intracranial aneurysm. In these situations, a stent may be necessary, leaving the interventionist to propose an antiplatelet regimen that prevents stent-associated thrombosis and thromboembolism while minimizing the risk of further hemorrhage.

If a stent is required in the setting of an acute intracranial hemorrhage, the glycoprotein (GP) IIb/IIIa inhibitor abciximab can be administered intra-arterially and locally at the site of recent stent deployment through the microcatheter. However, this should be done only after securing the culprit vascular lesion, such as a ruptured aneurysm. A bolus dose of 0.1 to 0.25 mg/kg is generally given, or a dose titrated to a GPIIb/IIIa receptor inhibition level of 50%. Immediately following the procedure, and after ensuring no hemorrhage at the arterial access site, a loading dose of ASA 325 to 650 mg and clopidogrel 300 mg daily for 2 days and then 75 mg thereafter should be implemented for dual antiplatelet therapy as described previously.

Acute Stroke

Stroke patients present several important challenges for the neurointerventionist. Many of these patients have preexisting vascular disease, are already on one or more antiplatelet medications, and, in addition, will have received intravenous tissue plasminogen activator (tPA) if they present within the 4.5-hour time window from the onset of symptoms.8 Furthermore, potential hemorrhagic conversion of the infarcted territory or reperfusion hemorrhage after successful revascularization are serious considerations that affect the choice of anticoagulation in these patients.

If IV tPA has recently been administered, and the patient becomes a candidate for an attempt at endovascular revascularization, it is reasonable to proceed without further anticoagulation. It is in general advisable not to administer antiplatelet or anticoagulant medications within 24 hours of treatment of IV tPA. It must be kept in mind, however, that tPA has a relatively short half-life (2 to 12 minutes) and that recommended time windows for endovascular revascularization are as long as 8 hours for anterior circulation strokes and up to 12 hours for basilar artery occlusions. Hence, if endovascular revascularization is attempted more than 1 to 2 hours after intravenous tPA administration or if none was given, then intravenous heparinization should be given soon after femoral access has been established to prevent the additional risk of thrombus formation associated with intra-arterial catheter manipulation as well as with endothelial injury from the various reperfusion methods available. If intravenous heparin is administered for attempted endovascular thrombolysis after intravenous tPA has been given, a postprocedure noncontrast computed tomography (CT) scan should be considered after the procedure to rule out any intracranial hemorrhage.

The specific revascularization strategy used for arterial stroke depends on the experience of the interventionist, and characteristics of the lesion itself. Intra-arterial thrombolysis has the theoretical advantage of higher doses of agent being directed at the target site, with lower systemic exposure. Currently, the only thrombolytic agent approved for intra-arterial use is tPA, although other nonthrombolytic agents such as GPIIb/IIIa inhibitors are being used at some centers. Intra-arterial tPA can be used as a therapeutic adjunct to IV tPA in patients who present within 6 hours of symptoms onset, and its use has been supported by several trials including the Emergency Management of Stroke (EMS) trial as well as the Interventional Management of Stroke (IMS-I) trial. According to the IMS-I trial, the microcatheter is first positioned beyond the thrombus and 2 mg of tPA is injected over a 2-minute period. The catheter is then retracted into the thrombus, and 2 mg of tPA is injected directly into the thrombus over another 2-minute period. Continuous infusion of tPA is then started at a rate of 9 mg/h for up to 2 hours or until thrombolysis is achieved. An ongoing IMS-III trial will further help to evaluate the effectiveness of combined IA and IV tPA therapy compared with IV tPA alone.

Several device options for arterial stroke revascularization are available, including simple mechanical clot disruption (with microcatheter or microwire), thrombus retrieval devices (Merci retriever, Concentric Medical, Mountain View, CA), stent-based retrieval devices (Solitaire, ev3 Endovascular Inc., Plymouth, MN; Trevo, Stryker, Morrisville, PA), mechanical and vacuum thrombolysis (Penumbra, Penumbra Inc., Alameda, CA), or venturi-based thrombectomy (AngioJet, Medrad Inc., Warrendale, PA). In many cases, these devices are being used as first-line therapies, with or without the addition of intra-arterial tPA. Tissue plasminogen activator (tPA) as an adjunctive treatment includes those occasions in which revascularization with the device methods reveals distal emboli (present since the onset of the symptomatic occlusion, or inadvertently caused iatrogenically during endovascular manipulations resulting in portions of thrombus migrating distally). In some instances, tPA is being used after failed mechanical revascularization. The intra-arterial dose of tPA used in these settings is typically administered in 1- to 3-mg aliquots with intermittent angiography to see if the desired effect has been achieved.

Cases of Venous Thrombosis

Endovascular treatment of dural sinus or deep cerebral vein thrombosis is increasingly common. The issues surrounding anticoagulation treatment for venous thrombosis are especially complex due to the propensity for hemorrhagic conversion of venous infarcts. Patients with venous thrombosis and without a significant intracerebral hemorrhage should be placed on intravenous heparin as soon as the diagnosis has been made. In patients being treated with intravenous heparin, whether or not to stop the heparin infusion prior to obtaining groin access is practitioner-dependent. If possible, access should be limited to the venous system, to avoid the added complexity of a potential arterial groin site complication in the setting of full heparinization.

As for arterial cases, several options for endovascular venous thrombolysis are available. These include simple mechanical clot disruption (with microcatheter or microwire), mechanical and vacuum thrombolysis (Penumbra), as well venturi-based thrombectomy (AngioJet). Restoration of at least some flow through the thrombosed venous channel is the goal, because this seems to predict persistent patency of the thrombosed venous segment. Instillation of tPA within the clot is often performed as with arterial thrombolysis cases. In our experience, however, venous thrombosis is particularly prone to reocclusion. For this reason, intravenous heparin should be administered continuously during the procedure as well as during the immediate postoperative period, and patients should subsequently be bridged to oral anticoagulation with warfarin once stabilized.

Another option for patients with venous thrombosis is locally administered tPA within the thrombus, followed by a continuous intrathrombus infusion of tPA with simultaneous intravenous heparin. According to this protocol, 1-mg boluses of tPA are first instilled at 1- to 2-cm intervals of the thrombosis, and then the microcatheter is repositioned just proximal to the rostral end of the thrombus and intravenous tPA is administered through the microcatheter over a period of 12 to 24 hours.9 Patients are treated with concomitant intravenous heparin at twice the control levels of PTT. After 12 to 24 hours of continuous treatment, patients are reimaged with contrast venography and are subsequently bridged to oral warfarin therapy.

Intraprocedural Thrombus

Despite attempts to prevent thrombus formation during endovascular procedures, including aggressive catheter and wire maintenance, continuous flushing of catheters with heparinized saline, avoiding catheter-induced spasm, pretreatment with antiplatelets for stenting procedures, and adequate systemic anticoagulation, thromboembolic complications are not uncommon. For the interventionist, it is important to remain vigilant in the interpretation of the angiographic images so that early thrombus formation does not go unrecognized and early treatment for the thrombus can be implemented.

The most common locations for thrombus formation are at the tip of a guide catheter, within a stent, or adjacent to a coil mass. In one series, thrombus was identified at the coil–parent artery interface in 4.3% of cases.¹⁰ Heparinized saline drips should be monitored frequently and blood flow beyond the tips of guide catheters should be checked intermittently to look for thrombus as well as spasm induced by rubbing of the catheter tip against the vessel wall. Low magnification angiograms of the entire territory supplied by the vessels being manipulated should be performed pre- and postprocedure, and should be scrutinized for occlusions or sluggish flow. Close attention should also be paid to changes in electrophysiological monitoring, such as somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) in patients who are under general anesthesia and the clinical exam in patients who are awake because, occasionally, these may be the first signs of a thromboembolic complication.

Platinum-based coils used for typical aneurysm embolization procedures are designed to promote thrombus formation at their site of deployment. They accomplish this primarily by the mechanism of electrothrombosis, in which the nondissolvable positive charged end of platinum attracts negatively charged blood constituents including red blood cells, platelets, and fibrinogen.⁵ Coils with various surface coatings have been developed to further invoke the thrombogenic response, such as those coated with the polymers polyglycolide and polylactide (Axium, ev3; Matrix, Siemens Healthcare, New York, NY). Coils that are closely adjacent to or herniating out of the neck of the aneurysm, therefore, may produce thrombus that can embolize distally. During an elective aneurysm coiling, if a misplaced coil cannot be retrieved, consideration can be given to placement of a stent to force the coil along the wall of the blood vessel. In either ruptured or unruptured cases, assuming the aneurysm is protected, the patient can be placed on ASA with or without clopidogrel to prevent a thromboembolic complication. The hemorrhagic risk of starting antiplatelet agents in a patient with subarachnoid hemorrhage after aneurysm occlusion is relatively low in our experience.

If thrombus is identified angiographically, the goal of management is to prevent progression to a clinically significant event. If there is complete occlusion of a vessel, the first steps in management include ensuring adequate hydration and raising the blood pressure. Intra-arterial tPA may be administered for a thrombolytic effect. The risk of a hemorrhagic event when tPA is used in the setting of an acutely ruptured aneurysm, however, is significant and should be avoided.6 Nonocclusive thrombus within a stent or associated with coils herniating into the parent vessel can be managed with antiplatelet agents, because they tend to be platelet-rich. To prevent recruitment of additional platelets and propagation of the thrombus, abciximab can be administered at a bolus dose of 0.1 to 0.25 mg/kg intra-arterially (in 2- to 5-mg aliquots) through a microcatheter positioned proximal to the thrombus.⁶ Alternatively, the entire calculated dose based on ideal body weight may be quickly given intravenously as a bolus to speed delivery. After groin hemostasis is achieved, the patient can be started on ASA with or without clopidogrel.

Strategies for Monitoring; Reversal of Anticoagulants/Antiplatelet Agents

Prior to procedures requiring the use of antiplatelet agents, such as elective stent placement, patients should be started on ASA and clopidogrel. Ideally, sensitivity to ASA and clopidogrel should also be verified prior to the procedure. Confirmation of platelet dysfunction can be done using either bleeding time or optical aggregometry. Alternatively, a point-of-care platelet function assay can be used, which is a bench-top unit using citrated whole blood and disposable test cartridges. ASA and clopidogrel resistance can be measured by assessing the response of platelets to the agonist adenosine diphosphate (ADP). Resistance to GPIIb/IIIa antagonists can be measured by the response of platelets to ADP as well as to other agonists such as thrombin receptor agonist peptides.

During the procedure, monitoring of ongoing intravenous heparinization is accomplished by means of the ACT. For most endovascular procedures, the ACT should be kept at 250 to 300 seconds, or at least double the baseline value. The ACT is determined by a bench-top analyzer that uses a mechanical clot detection mechanism. In this assay, whole blood is exposed to an activator of coagulation. A magnet is displaced once clot formation occurs, activating the alarm, and an ACT is reported. Typically, the first ACT is drawn 5 minutes after heparinization. Levels should be repeated every 30 to 45 minutes and again after completion of the procedure.

Upon completion of the endovascular procedure performed with full heparinization, the interventionist has the option of reversing anticoagulation. Pharmacological reversal can be performed with protamine at 1 to 1.5 mg for every 100 U of heparin given. We recommend checking the ACT at the end of the procedure and prior to removal of the access sheath, because if the ACT has already drifted into the normal range in an uncomplicated case, then pharmacological reversal may not be required. In a case that is uncomplicated but with the propensity for hemorrhage in the early postoperative period, reversal prior to arterial sheath removal is suggested. In a case complicated by a hemorrhagic event, however, early and rapid reversal of anticoagulation should be instituted.

For procedures in which the risk of a thromboembolic complication is present primarily during the procedure itself, such as AVM, arteriovenous fistula (AVF), or tumor embolizations, reversal of anticoagulation prior to removal of the arterial sheath should be considered. Alternatively, the PTT can be checked 6 hours after procedure and, if normalized, the sheath can be removed at that time. Delayed removal, however, can lead to clot formation within or on the sheath, or femoral arterial dissection from excessive movement of the leg.

For patients with recent arterial stroke in whom tPA was not administered, it is reasonable to continue intravenous heparin in the postoperative period. Arterial sheath removal for these patients can be performed on a delayed basis 12 to 24 hours after the procedure, by first stopping the intravenous heparin for 2 hours and confirming a normal PTT prior to removal. Intravenous heparin may be resumed after hemostasis at the access site is ensured. Similarly, venous thromboembolism patients should be continued on intravenous heparin because reocclusion rates in these patients are high. After the thrombolysis procedure, the PTT should be maintained at therapeutic levels after the procedure with intravenous heparin, with or without a continuous microcatheter infusion of intravenous tPA at the site of thrombosis as previously described. A follow-up venogram is often performed the following day and, if the cerebral venous system has remained patent, the intravenous heparin can be temporarily stopped, the sheath removed, and heparin resumed. Subsequently, the patient can be bridged to oral anticoagulation with warfarin.

If a procedure is complicated by intracranial hemorrhage, such as an aneurysm perforation, the anticoagulation should be immediately reversed with protamine. Other measures used to prevent additional bleeding include lowering the blood pressure, expeditiously coiling the aneurysm, and balloon inflation across the aneurysm neck within the parent vessel. Evidence of hemorrhage at the femoral access site, such as constant oozing, a visibly enlarging hematoma, drop in hematocrit, or unexplained hypotension should be reason to reverse the anticoagulation, and an immediate CT scan of the abdomen/pelvis should be obtained.

Role for Anticoagulants/Antiplatelet Agents Postembolization

In several instances, there is a role for continued treatment with anticoagulants or antiplatelet agents following embolization. These include procedures entailing thromboembolic complications, stroke (of arterial and venous etiologies), and after placement of a carotid or intracranial stent.

For thromboembolic complications, there is no evidence to guide the specific management and duration for antiplatelet therapies. If the thromboembolic event occurred secondary to a permanent and thrombogenic foreign body, then the ASA should be started after the procedure and continued indefinitely. It is recommended, however, to obtain a noncontrast CT after the procedure to rule out a hemorrhagic complication prior to beginning antiplatelet therapy. Clopidogrel may be used in addition to ASA, especially if the patient experiences symptoms from the thrombus, and consideration can be given to discontinuing the clopidogrel after 4 to 6 weeks in the patient without recurrent symptoms. For thromboembolic events that occur in the setting of a subarachnoid hemorrhage and after the aneurysm has been secured, the risk of antiplatelet therapy is low. If thromboembolism occurred secondary to a transient cause such as that related to the guide catheter, then antiplatelet therapy can be instituted for a temporary period (2 to 4 weeks).

For secondary prevention in patients with noncardioembolic stroke or TIA, current recommendations are for oral antiplatelet regimens as opposed to oral anticoagulation. ASA and dipyridamole in combination are recommended over ASA therapy alone. Alternatively, clopidogrel monotherapy may be used. The combination of ASA and clopidogrel, however, is not routinely recommended due to the risk of hemorrhage unless, however, there is a specific indication for both medications such as after placement of a carotid or intracranial stent. For patients with cardioembolic stroke or TIA due to atrial fibrillation, oral anticoagulation with warfarin to a target INR between 2.0 and 3.0 is recommended. Dabigatran, a direct thrombin inhibitor, is an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. The timing for initiation of anticoagulation in stroke patients is debated. In general, anticoagulation should be started within 2 weeks of an ischemic stroke. For patients unable to take warfarin, ASA 325 mg daily is recommended.

As described previously, following stent placement dual antiplatelet therapy with ASA 325 mg and clopidogrel 75 mg is recommended for 6 weeks to 3 months, followed by ASA 325 mg indefinitely thereafter. In the case of drug-eluting stents, such as those occasionally placed for large-vessel extracranial disease, a 6-month to 1-year course of dual antiplatelet therapy is required because of the longer period required for endothelialization. Stents typically used for aneurysm neck remodeling are only rarely associated with delayed in-stent restenosis, unlike those placed for atherosclerotic disease. Nevertheless, nearly all stents produce considerable artifact on CT and magnetic resonance imaging (MRI), so follow-up conventional angiography may be considered 6 weeks to 3 months postprocedure to reassess the original lesion, search for in-stent restenosis, and determine subsequent antiplatelet management.