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Neoatherosclerosis is one of the multiple mechanisms that cause stent thrombosis, which is one of the rare but severe complications of drug-eluting stent implantation. This case study highlights the use of optical coherence tomography in identifying the precise mechanism of the stent thrombosis, which helped guide the appropriate intervention.

Objectives: To assess early vascular healing with endothelial progenitor cell (EPC)-capturing stents., Background: Endothelialization of stent struts is crucial after stenting, since delayed vascular healing predisposes to stent thrombosis. The antibody-coated Genous stent promotes rapid endothelialization by capturing circulating EPCs., Methods: We enrolled 20 patients who had EPC-capturing stent implanted in the left anterior descending (LAD) coronary artery. Patients underwent optical coherence tomography 30 days following the index procedure. Coronary flow reserve (CFR) was assessed in the LAD by transthoracic echocardiography at 30 days., Results: After follow-up of 31.8 ± 5.3 days, the binary stent strut coverage was 95% and the percentage of malapposed struts was 2.4%. No thrombi were detected. The mean neointimal hyperplasia (NIH) thickness was 108 ± 96 μm and the percent NIH area was 8.9 ± 7.4%. The mean CFR was 2.4 ± 0.7., Conclusions: The EPC-capturing stent showed rapid endothelialization, low NIH area, and few malapposed struts at 30 days.

This work describes the longest reported interval between drug-eluting stent (DES) placement and very late stent thrombosis (VLST). A 69-year-old male presented with substernal chest pain associated with ST-segment myocardial infarction (STEMI) after having a DES deployed 6.9 years (2506 days) prior. The patient's medical history revealed several risk factors for VLST. The patient suspended clopidogrel therapy in preparation for elective cystoscopy approximately 10 days before presenting.

Background: Patients with metabolic syndrome (MetS) are at increased risk of cardiovascular events. The long-term effectiveness of sirolimus-eluting stents (SES) in patients with MetS and in diabetic patients is not well defined., Methods: 563 consecutive patients with 629 de novo coronary lesions (< 50 mm lesion length, reference diameter < 3.5 mm) successfully treated with SES were enrolled in the study and followed for 41 +/- 17 months. Bifurcation and left main lesions were excluded. Patients were categorized into three groups: 1) no MetS and no diabetes; 2) MetS and no diabetes; and 3) diabetes. MetS was defined as the presence of > or = 3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, elevated fasting glucose., Results: 284 patients (51%) with 318 lesions had neither MetS nor diabetes, 148 patients (26%) with 163 lesions had MetS without diabetes and 131 patients (23%) with 148 lesions had diabetes. Baseline angiographic parameters were comparable between the three groups. Clinically driven target lesion revascularization rates for controls, MetS and diabetics were 7.7%, 5.4% and 14.5%, respectively (p = 0.041). Mortality rates for the three groups were 4.2%, 10.1% and 15.3%, respectively (p = 0.042). There were also significant differences in stent thrombosis (ST) rates with 0.3% in controls, 0.6% in MetS and 6.1% in diabetics (p = 0.037). Annual mortality and ST rates for controls, patients with MetS and diabetic patients were 1.2%, 3.0% and 5.6% (p = 0.037) and 0.2%, 0.3% and 2.7% (p = 0.039), respectively. Late loss in-lesion was 0.19 +/- 0.59 mm in controls, 0.17 +/- 0.44 mm in patients with MetS/no diabetes and 0.46 +/- 0.81 mm in diabetics (p < 0.001)., Conclusion: During long-term follow up after implantation of SES in de novo coronary lesions, MetS without diabetes does not result in an increase in target lesion revascularization or ST rates compared with control patients. However, patients with MetS have a higher follow-up mortality rate compared to control patients.

We performed a pooled analysis of three trials comparing titanium-nitride-oxide-coated bioactive stents (BAS) with paclitaxel-eluting stents (PES) in 1,774 patients. All patients were followed for 12 months. The primary outcomes of interest were recurrent myocardial infarction (MI), death and target lesion revascularization (TLR). Secondary endpoints were stent thrombosis (ST) and major adverse cardiac events (MACE) including MI, death and TLR. There were 922 patients in the BAS group and 852 in the PES group. BAS significantly reduced the risk of recurrent MI (2.7% vs. 5.6%; risk ratio 0.50, 95% CI 0.31-0.81; p = 0.004) and MACE (8.9% vs. 12.6%; risk ratio 0.71, 95% CI 0.54-0.94; p = 0.02) during the 12 months of follow up. In contrast, the differences between BAS and PES were not statistically significant with respect to TLR (risk ratio 0.98, 95% CI 0.68-1.41), death (risk ratio 0.96, 95% CI 0.61-1.51) and definite ST (risk ratio 0.28, 95% CI 0.05-1.47). In conclusion, the results of this analysis suggest that BAS is effective in reducing TLR and improves clinical outcomes by reducing MI and MACE compared with PES.

Background: The optimal combination of anticoagulant and antiplatelet therapy following percutaneous coronary intervention with stenting (PCI-S) among patients requiring oral anticoagulation (OAC) is unknown., Objectives: We sought to compare the efficacy of a modified dual-antiplatelet regimen (daily aspirin and every other day clopidogrel) to conventional treatment (daily aspirin and daily clopidogrel) following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) among patients who are also discharged on warfarin., Methods: We performed a single-center, retrospective analysis of consecutive patients (n = 454) who underwent PCI-S with DES and were discharged on warfarin and either a conventional (n = 170) or modified (n = 284) antiplatelet regimen between March 2003 and May 2007. In-hospital and 1-year events were compared between the two groups., Results: There were no differences in 1-year rates of death, myocardial infarction, stent thrombosis or target lesion revascularization between patients receiving a conventional compared to a modified antiplatelet regimen. In-hospital bleeding rates were also similar between the two groups., Conclusions: An antiplatelet regimen of aspirin with every-other-day clopidogrel may be as efficacious as daily aspirin and clopidogrel among patients receiving warfarin following PCI-S with DES.

Background: Semisynthetic coating of the Camouflage bare-metal stent (BMS) (Eucatech AG, Rheinfelden, Germany) mimics luminal endothelial cell glycocalix, potentially preventing the activation of the coagulation system. Purpose. We sought to determine in a clinical registry the acute and long-term clinical and angiographic outcomes of this BMS design in patients with acute coronary syndromes (ACS) or who were unable to be on long-term clopidogrel therapy., Methods: From March 2007 to December 2008, 150 patients undergoing coronary stent implantation at three centers in Buenos Aires, Argentina, were included in our registry. Patients with ACS, including non-ST-elevation myocardial infarction (NSTEMI) and STelevation MI (STEMI), or those unable to be on long-term dual antiplatelet therapy were considered for inclusion. The primary endpoint was a major adverse cardiovascular event (MACE) defined as the incidence of cardiac death, MI or target lesion revascularization (TLR). The incidence of acute and late stent thrombosis (ST) was also analyzed. Angiographic late loss and the presence of late stent malapposition (LSM) was recorded at 9-month follow up. Clopidogrel was prescribed for 1 month., Results: 54.7% of patients had acute MI, 36% had STEMI and 20.7% of patients were ineligible for long-term clopidogrel therapy because of previously planned non-vascular or general surgery within 30 days after percutaneous coronary intervention. During 11.5 months of clinical follow up, 2% suffered cardiac death, 4% had a MI, 8.9% underwent TLR and the overall cumulative major adverse cardiac event rate was 15.3%. No patient developed acute or late ST. There were no in-hospital complications for patients who underwent surgery. Intravascular ultrasound studies did not detect the presence of late malapposition., Conclusion: In this high-risk thrombotic patient population, the Camouflage coated stent design demonstrated a very good safety profile, as reflected by the low incidence of hard adverse cardiac events including ST at follow up.

A 56-year-old male was admitted for elective percutaneous coronary intervention. Four days later he developed subacute stent thrombosis in the proximal stent in his right coronary artery. Using the Multiplate(R) ASPI and ADP test, we detected combined aspirin and clopidogrel resistance. The doses of aspirin and clopidogrel were increased to 300 mg and 150 mg, respectively. This resulted with optimization of aspirin response, but clopidogrel resistance was doseindependent. Three days later, the patient developed a new episode of ST-elevation myocardial infarction due to recurrent subacute thrombosis in the proximal stent. Consequently, clopidogrel was switched to ticlopidine 250 mg twice daily with resultant optimal platelet inhibition in the ADP test and the patient became clinically stable. This case indicates the clinical benefit from routine assessment of platelet responsiveness to antiaggregation therapy in patients with stent thrombosis. Also, clopidogrel resistance is drug-specific and not necessarily a class-effect phenomenon. By modifying drugs' doses, type of thienopyridine, or both, we can optimize antiplatelet therapy and the clinical course.

Unlabelled: MGuard is a bare-metal stent covered by an ultrathin polymer mesh sleeve on its external surface, designed to reduce embolization during coronary, cerebrovascular and peripheral interventions., Aim: To evaluate the feasibility and safety of MGuard-based percutaneous coronary interventions (PCIs) of human native coronary arteries (NCs) and coronary vein grafts (VGs)., Methods: MGuard-based PCI executed by 2 centers with postprocedural clinical and laboratory monitoring; including creatinine phosphokinase (CPK), troponin, electrocardiography and 6-month angiographic follow up. The primary endpoint was 30-day major adverse cardiac events (MACE) including cardiac death, myocardial infarction, stent thrombosis and repeat target lesion revascularization. The secondary endpoint was device and procedural success., Results: Twenty-nine patients with a mean age of 68.1 +/- 12 years were enrolled. The mean VG age (n = 17) was 12.6 years (range 8-19). All patients received heparin, clopidogrel and aspirin, while none received bivalirudin, glycoprotein IIb/IIIa inhibitors (GPIs) or an embolic protection device (EPD). Device and procedural success were 100% and 96.5%, respectively. One patient experienced a procedure-related CPK rise. No MACE were reported at 1 month., Conclusion: MGuard-based PCI of NCs and VGs appears encouraging, especially in view of unfavorable patient and lesion characteristics. Both efficacy and safety need to be further established in larger-scale studies with longer follow-up periods.

In patients with acute ST-elevation myocardial infarction or in those with thrombus-containing lesions, percutaneous coronary intervention (PCI) represents a clinical challenge to the interventionist, because coronary thrombus is a predictor of adverse outcomes. Thrombectomy, or the removal of thrombusfrom the infarct-related vessel prior to PCI, might improve clinical outcomes. The AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota) is commonly used to treat lesions containing thrombus burden. A complication of rheolytic thrombectomy is transient cardiac rhythm disturbances, specifically bradyarrhythmia requiring temporary pacing. Aminophylline, a methylxanthine and a competitive inhibitor of the adenosine receptor, may prevent rheolytic thrombectomy-associated bradyarrhythmias. This report describes the use of aminophylline alone to prevent rheolytic thrombectomy-induced bradyarrhythmias in a single tertiary care center.

The main goal of treatment for ST-segment elevation myocardial infarction (STEMI) is prompt and complete reperfusion of the infarcted myocardium. This may be achieved using either fibrinolytic agents or primary percutaneous coronary intervention (PPCI, involving angioplasty with or without coronary artery stenting). In the clinical trial setting, PPCI appears to yield superior results. However, this treatment option is frequently either unavailable or associated with unacceptably long delays between symptom onset and reperfusion. In contrast, fibrinolytic therapy is almost universally available and, in the absence of contraindications, can even be initiated before hospital arrival. The success of fibrinolytic treatment is likely to improve as advanced pharmacological regimens are explored. For example, one of the main disadvantages of standard fibrinolytic therapy is that, paradoxically, it increases thrombin production and platelet aggregation. There is thus a rationale for combining fibrinolysis with aggressive antiplatelet therapy. The use of aspirin is now universal in fibrinolytic-treated patients, and the use of a thienopyridine (such as clopidogrel) appears to be beneficial, but additional antiplatelet inhibition using a platelet glycoprotein IIb/IIIa inhibitor (such as abciximab or eptifibatide) is controversial. Adjunctive use of antithrombotic therapy is also beneficial during fibrinolytic treatment. This review outlines the growing list of treatment options available for these high-risk patients and highlights the advantages of some of the newer pharmacological strategies.

Objectives: Stent thrombosis (ST) is a recognized complication of percutaneous coronary interventions (PCI). Due to the high thrombus burden present in ST, the use of thrombus aspiration (TA) may enhance the angiographic results by limiting distal embolization., Methods: Consecutive patients undergoing urgent PCI due to ST were studied, consisting of two groups according to the type of intervention (standard PCI [SP] or TA). TIMI flow, corrected TIMI frame count (cTFC), myocardial blush grade (MBG), thrombus score (TS), Yip's adverse thrombus burden features, occurrence of angiographically evident distal embolization (DE) were evaluated offline. In-hospital outcomes were also recorded., Results: Twenty-eight patients entered the study. Baseline clinical and angiographic features were similar between patients treated by SP (n = 12) and those treated by TA (n = 16). After PCI, a trend in favor of TA as compared to SP was observed for post-PCI TIMI 3 flow rate (67% vs. 89%; p = 0.10), final cTFC (31 +/- 35 vs. 17 +/- 21; p = 0.10) and MBG 2-3 rate (40% vs. 67%; p = 0.12). Accordingly, the rate of adverse angiographic outcome (post-PCI TIMI 0-1 flow and/or DE) was significantly lower in the TA as compared to SP: 5% (1 out of 18) vs. 33% (5 out of 15) respectively (p = 0.04). Throughout hospitalization, major adverse events occurred in 6% of TA patients vs. 33% of SP patients (p = 0.08)., Conclusions: TA in patients with ST is safe and is associated with better angiographic outcomes compared to standard PCI. Larger studies are warranted to confirm these early observations.

Stent thrombosis is a potentially catastrophic complication of coronary artery stenting. There have been particular concerns about the incidence of stent thrombosis following insertion of drug-eluting stents. We report a series of cases in which stent thrombosis occurred in association with malignancy and describe the potential mechanisms behind such an association. We speculate that this association merits further investigation as it raises the possibility that known malignancy may be a risk factor for stent thrombosis and that unexplained stent thrombosis, particularly if recurrent, should stimulate a search for occult malignancy.

Objectives: This study compared acute and late outcomes following a strategy of selective drug-eluting stent (DES) use guided by a set of 4 criteria defining higher risk of in-stent restenosis compared to an exclusive DES strategy in 362 patients with multilesion (n = 900) percutaneous coronary interventions., Results: At a mean follow up of 412 +/- 110 days, major adverse cardiac events (death, myocardial infarction, revascularization) were 16.8% in the exclusive DES group compared to 18.4% in the selective DES group (p = 0.78). By univariate analysis, revascularization rates (9.9% in the exclusive DES group versus 10.5% in the selective DES group; p = 1.0) and target lesion revascularization (TLR) rates (5.5% versus 6.2%; p = 0.77) were similar in the 2 groups. By multivariate analysis adjusted by propensity score to account for differences in baseline characteristics, the strategy of exclusive DES use was not associated with lower risks of revascularization (hazard ratio [HR]: 0.91, 95% confidence interval [CI] 0.64-1.29) or TLR (HR: 0.81, 95% CI 0.59-1.08) compared with selective DES use. Using the Academic Research Consortium criteria, stent thrombosis occurred in 6/161 (3.7%) cases in the exclusive DES group and in 1/201 (0.5%) case in the selective DES group (p = 0.03)., Conclusions: In patients with multiple coronary lesions, a selective DES strategy for lesions at higher risk of restenosis and bare-metal stents for other lesions was safe and effective when compared to the exclusive use of DES. A large, prospective, randomized trial is required to validate a criteria-based selective DES strategy compared to systematic DES use.

Despite recent meta-analyses showing either similar rates or only slightly increased rates of stent thrombosis in patients with a drug-eluting stent, clinicians remain concerned about the risk of late stent thrombosis in these patients. We are reporting on a "very-very" late stent thrombosis that occurred 43 months post-implantation. We believe this represents the most delayed reported thrombosis post-sirolimus-eluting stent implantation, which might not have been preventable using even the latest FDA recommendations.

Background: Conflicting opinion exists regarding the optimal dose of acetyl salicylic acid (ASA) to be given after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). We sought to evaluate the influence of ASA dose on the incidence of unexplained subacute and late stent thrombosis in the era of DES., Methods: We performed a retrospective analysis of the incidence of subacute and late stent thrombosis in our patient population over a 2-year period. The analysis was limited to patients being discharged and maintained on a daily ASA dose of either 81 mg or 325 mg and having received at least 1 sirolimus-eluting stent., Results: During the study period, 1,093 patients (1,807 separate PCI procedures) met the inclusion criteria. The incidence of unexplained subacute and late stent thrombosis was 1.1% in the study population (12 out of 1,093 patients). When considering the total number of individual procedures performed on the study population during the study period (1,807 procedures), the incidence of unexplained subacute or late stent thrombosis was 0.7%. Six were subacute and 6 were late thrombosis. No significant difference was observed in the incidence of stent thrombosis between the 2 ASA dose groups. Seven patients had stent thrombosis in the 81 mg group (1.2% of 583 patients), while 5 had thrombosis in the 325 mg group (1% of 510 patients); p = 0.727., Conclusion: In conclusion, we found no significant difference in the incidence of unexplained subacute or late stent thrombosis with the use of an 81 mg versus 325 mg dose of aspirin post-PCI with sirolimus-eluting stents.

We describe a novel approach for the use of a FilterWire EX distal protection device as a snaring device for clot extraction in a patient who sustained acute ST-elevation myocardial infarction due to occlusion of the right coronary artery.

Objective: Stent thrombosis and in-stent restenosis remain problematic despite drug-eluting stents (DES), especially in diabetic patients and in those with small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both thrombosis and proliferation. The aim of the present studies was to examine the absorption and elution characteristics of eptifibatide on polymer-coated stents and investigated their effect on SMC proliferation, platelet deposition and platelet aggregation in vitro., Methods and Results: Polymer-mixed eptifibatide and H3-labeled eptifibatide were loaded onto bare metal stents. A maximum of 111 mcg of eptifibatide was loaded onto 3.0 x 18 mm stents. Drug elution characteristics were tested in a PBS perfusion circuit. Elution profile consisted of an early rapid phase (24% +/- 0.03 loss over 1 hour) followed by a sustained release with 44% +/- 2.30 still present on the stent after 30 days. Eluted eptifibatide significantly inhibited adenosine diphosphate (ADP)-induced platelet aggregation by 95% +/- 0.70 (p < 0.01). Efficacy of stents eluting eptifibatide for antiplatelet effect was determined by measuring deposition of 111indium-labeled platelets on stents. Platelet deposition was significantly reduced by 48% +/- 6 in comparison to controls (p = 0.0065). Finally, drug-loaded stents were placed in SMC culture and showed a distinct zone of cell growth inhibition within 1 mm2 (88 +/- 22 vs. 208 +/- 23 SMCs in control), and within 2 mm2 of stent (131 +/- 32 vs. 191 +/- 23 SMCs in control) (both p < 0.01)., Conclusions: Eptifibatide can be successfully loaded onto stents. It elutes in a predictable manner, significantly inhibiting platelet deposition, aggregation and SMC proliferation in vitro. These studies pave the way to developing stent-based delivery of a potent antiplatelet agent, which additionally may inhibit SMC activity.

Aims: Restenosis has been the principal limitation of bare metal stents. Based upon the presumption that platelet and inflammatory cell recruitment initiate neointimal proliferation, we explored a novel polymer coating that reduces cell-stent interactions. The purpose of the present study was to investigate the effect of poly(L-lysine)-graft-poly(ethyleneglycol) (PLL-g-PEG) adsorbed to stent surfaces to reduce neointimal hyperplasia in the porcine restenosis model., Methods and Results: Seven animals were instrumented each with 2 stainless steel stents (15 mm length, 2.5-3.5 mm diameter), randomly implanted in 1 major epicardial coronary artery. One stent was dip-coated with PLL-g-PEG, whereas the other stent served as the uncoated control stent. All animals were sacrificed after 6 weeks for histological examination. Neointimal hyperplasia was significantly less (-51%) in the PLL-g-PEG-coated stents (1.15 +/- 0.59 mm2) than in the uncoated control stents (2.33 +/- 1.01 mm2; p < 0.001). Conversely, lumen size was larger in the PLL-g-PEG-coated stents (2.91 +/- 1.17 mm2) than in the uncoated stents (2.04 +/- 0.64 mm2; p < 0.001). High magnification histomorphologic examination revealed no signs of inflammation or thrombus formation in either stent group., Conclusions: Polymeric steric stabilization of stents with PLL-g-PEG significantly reduces neointimal hyperplasia in the porcine restenosis model. Reduction of cell-stent interactions mediated by PLL-g-PEG appear to improve biocompatibility of stainless steel stents without evidence of adverse inflammatory or prothrombotic effects.

Stent thrombosis is a catastrophic event characterized by the acute thrombotic occlusion of a previously-stented segment of a coronary artery. It usually presents as an ST-segment elevation myocardial infarction and/or death, and most commonly occurs within the first several weeks after stent placement. Stent thrombosis is classified as either subacute stent thrombosis (SAT), occurring within 30 days of stent placement, or as late stent thrombosis (LST), occurring after 30 days. While very late stent thrombosis (VLST), occurring beyond 1 year, is not uncommon with the use of drug-eluting stents, it is distinctly unusual with the use of bare-metal stents. We report a case of very late thrombosis of a bare-metal stent occurring 717 days after implantation.

In the area of drug-eluting stents (DES), complex interventional procedures are increasing in number. In particular, the number of patients undergoing three-vessel or bifurcation lesion stenting is rising, together with increasing concern about the risk of acute stent thrombosis in the area of the DES. In this paper, we present a patient who underwent multivessel bifurcation stent placement after an acute inferior myocardial infarction over a period of one week, with sudden subacute stents thrombosis of the two drug-eluting stents in the left anterior descending and the circumflex coronary arteries, leading to death. This case report is followed by a review of literature.

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare but potentially fatal adverse reaction to the thienopyridines, clopidogrel and ticlopidine. We report the case of a patient with a history of clopidogrel-induced TTP who subsequently was successfully treated with aspirin, ticlopidine and cilostazol after stenting for severe, symptomatic coronary artery disease. This case supports the theory that clopidogrel and ticlopidine mediate TTP through slightly different mechanisms and that ticlopidine may be safely used in this setting if absolutely necessary. Moreover, while sufficient data are lacking, the combination of aspirin and cilostazol in this setting may provide adequate antithrombotic protection long term after drug-eluting stent placement.

The hallmark of acute ST-segment elevation myocardial infarction is complete thrombotic occlusion of the infarct-related artery. Reperfusion strategies over the past 25 years have focused on the early restoration of flow in the epicardial artery. More recently, through enhanced understanding of the microvasculature, the open artery hypothesis has moved downstream to also include the complete and early restoration of microvascular flow. Fibrinolytic monotherapy has a ceiling of efficacy, but is universally available. Improvement of early artery patency can be achieved with the addition of a platelet glycoprotein IIb/IIIa receptor antagonist. Mechanical revascularization, via percutaneous coronary intervention, is superior to pharmacologic therapy, but can have limited accessibility. Perhaps the optimal strategy will involve a combination of pharmacologic and mechanical modalities.

Atherosclerosis, with its thromboembolic complications (including sudden cardiac death, myocardial infarction, and other ischemic organ damage such as stroke and ischemic renovascular disease), represents by far the major cause of death, morbidity, and disability for industrialized countries, and is rapidly spreading worldwide. Atherosclerosis is also a paradigm for complex, multifactorial disorders that affect humans in an age-dependent fashion. Atherosclerosis has usually been studied in a descriptive framework of biological and clinical data gathered over more than a century. As such, it is a chronic inflammatory process that selectively affects arterial vessels, and is, at least in part, genetically predetermined. Despite spectacular progress in the cardiovascular discipline, with the development of therapeutic strategies that have substantially improved the outcome of affected patients, several key questions remain unanswered: Why is aging such a powerful risk for coronary artery disease? What is the triggering mechanism for atherosclerotic inflammation? Also, in the context of this and accompanying reviews, do we modify coronary inflammation with glycoprotein IIb/IIIa blockers? Recent progress in our understanding of the underlying process of atherosclerosis has provided us with the opportunity to refine the answers to some of these questions.

Advances in percutaneous coronary intervention (PCI) have emerged in the past decade. Stenting has improved upon the limitations of angioplasty, acute vessel closure and restenosis by providing mechanical vascular support, resulting in sustained clinical and angiographic benefit. This has led to greater utilization of the technique, although it is associated with a significant incidence of in-stent restenosis. Neointimal hyperplasia is the pathophysiologic process that leads to in-stent restenosis. Brachytherapy can be effective in reducing the occurrence of this process. Unfortunately, brachytherapy trials have identified the phenomenon of late stent thrombosis as a potentially serious complication of this procedure. Late stent thrombosis is thrombosis that occurs > 30 days after PCI. The risk of thrombosis is increased in patients receiving a new stent in addition to brachytherapy. It also appears to be increased when adjunctive antiplatelet therapy with ticlopidine or clopidogrel is discontinued early. Strategies to prevent late stent thrombosis include the prolonged use of combination antiplatelet therapy in addition to limited placement of new stents in patients treated with brachytherapy for in-stent restenosis.

The two structurally related thienopyridines, ticlopidine and clopidogrel in addition to aspirin, have become the standard regimen for prevention of subacute thrombosis (SAT) after coronary stent implantation. Although both regimens are highly effective, ticlopidine suffers from severe hematologic side effects. Recent trials encourage shorter duration of therapy with these agents. However, the optimal duration of antiplatelet therapy after stenting is still not clear. We report a case of SAT developing 12 days after discontinuation of 2 weeks of aspirin plus ticlopidine therapy. We believe that the present data are still not clear regarding the optimum duration of antiplatelet therapy after stenting.

Although heparin is widely used to treat arterial thrombosis, it has limitations in this setting. These limitations reflect heparin's inability to inactivate fibrin-bound thrombin, a major stimulus for thrombus growth, and the fact that heparin is neutralized by platelet factor 4, large quantities of which are released from platelets at the site of plaque rupture. Heparin also has a propensity to bind non-specifically to other plasma proteins. Because plasma levels of these heparin-binding proteins vary from patient to patient, the anticoagulant response to heparin is unpredictable and careful laboratory monitoring is necessary to ensure that an adequate anticoagulant effect is achieved. Direct thrombin inhibitors, such as bivalirudin and hirudin, overcome many of the limitations of heparin. These agents inhibit fibrin-bound thrombin, as well as fluid-phase thrombin. Direct thrombin inhibitors also produce a more predictable anticoagulant response than heparin because they do not bind to plasma proteins and are not neutralized by platelet factor 4. Bivalirudin appears to have a wider therapeutic window than hirudin. Because this may permit administration of higher doses of bivalirudin, this agent may also have an efficacy advantage over hirudin. Differences observed between hirudin and bivalirudin demonstrate that not all direct thrombin inhibitors have the same risk-benefit profile.

Thrombo-occlusive events at sites of atherosclerotic stenosis and plaque rupture are caused by exposure of the sub-endothelial layer of the vasculature to platelets and their subsequent aggregation at the locus of injury. Thrombi are generated by the activation of platelets, which are not always inhibited by aspirin or heparin. Both unstable angina and myocardial infarction are ultimately linked to thrombus formation. In addition, various invasive procedures used to re-establish patency of coronary vessels are often followed by thrombotic events that can be life threatening. New antagonists to thrombin and the development of glycoprotein (GP) IIb/IIIa platelet receptor inhibitors have been the main focus of recent large clinical trials that have demonstrated both the efficacy and safety of these new agents. The new antithrombotics include hirudin, hirulog, and the low molecular weight heparins. Representative GP IIb/IIIa receptor blockers include: abciximab, a human-murine chimeric monoclonal antibody; tirofiban, a non-peptide tyrosine derivative with a short half-life; and eptifibatide, a cyclic heptapeptide. All three are available for clinical use, but their approved indications vary. The GP IIb/IIIa receptor antagonists are anticipated to gain wide clinical acceptance by both cardiologists and internists and should have a prominent role in the management of acute coronary syndromes, most likely in combination with an antithrombin.

Restenosis persists as an important factor limiting a favorable long term outcome following mechanical revascularization. The objective of the present study was to compare the effects of an intracoronary heparin treated tantalum prototype stent and balloon angioplasty on intimal hyperplasia, luminal diameter, and thrombosis in a porcine restenosis model. Male miniswine maintained on a high cholesterol diet and 325 mg aspirin per day underwent cardiac catheterization and oversized balloon injury to the right and left circumflex coronary arteries. Two weeks later one artery was either balloon injured again or implanted with a stent. No additional anticoagulation following stent placement was given, however aspirin was continued throughout the study. At four weeks, the coronary arteries were harvested and prepared for histologic examination and blinded quantitative morphometric analysis. The prototype stent was successfully deployed in 10 coronary arteries. Histological examination at explant revealed no evidence for thrombus or platelet aggregation. The angiographic luminal diameter of stented vessels was not significantly different from the diameter measured prior to implantation. In contrast, the angiographic diameter of balloon injured vessels was significantly decreased (4.4 +/- 0.4 mm2, balloon injured, vs. 5.8 +/- 3.3 mm2, control; p < 0.05). Stented arteries showed significantly more intimal hyperplasia, compared to balloon injured vessels (2.99 +/- 0.58 mm2 intimal area, stented arteries vs. 0.38 +/- 0.15 mm2 intimal area, control arteries; p < 0.05). In conclusion, heparin treated tantalum wire prototype intracoronary stents were successfully deployed in swine coronary arteries with no evidence for thrombus formation. Despite a significant intimal response, luminal diameter was preserved in stented vessels. The data suggest that a heparin treated tantalum wire prototype intracoronary stent may be an effective method of coronary revascularization that results in the preservation of luminal diameter without thrombotic occlusion.

Intracoronary stents can be implanted with a low incidence of stent thrombosis (< 1%) when the stent procedure is guided by intravascular ultrasound. The long-term clinical and angiographic effects, however, have not been reported. This study assesses the 6 month clinical and angiographic results of a consecutive series of patients with intravascular ultrasound guided Palmaz-Schatz stent deployment that were not treated with subsequent anticoagulation after a successful stent implantation procedure. From March, 1993 to April 1994, 411 patients underwent Palmaz-Schatz stent implantation. There were 26 patients that had uncomplicated Palmaz-Schatz stent implantation that were treated with a standard anticoagulation regimen that are not evaluated in this study. Thus, this study includes an assessment of 385 patients that had either a successful intravascular ultrasound guided stent implantation procedure and did not receive post procedure anticoagulation or had a procedural complication. Procedural success was achieved in 369 patients (96%). Clinical success (procedure success without early post procedure event) was achieved in 363 patients (94%). There were 2 acute stent thrombosis events (0.5%) and 1 subacute stent thrombosis (0.3%) in the group of 369 patients with 454 lesions treated without anticoagulation. At 6 month clinical follow-up the incidence of myocardial infarction was 4.9% and the rate of coronary bypass surgery was 6.2%. There was a 2.1% incidence of death. Emergency intervention (emergency angioplasty or bailout stent implantation was necessary in 3 patients (0.8%). The total incidence of repeat percutaneous intervention was 11.4%. By 6 months clinical follow-up, major events had occurred in 19.2% of patients. The angiographic lesion restenosis rate, according to 50% diameter stenosis criteria, was 19%. The incidence of restenosis per patient was 22%. In conclusion, intravascular ultrasound guided Palmaz-Schatz can be performed without subsequent anticoagulation with a low incidence of stent thrombosis and acceptable clinical and angiographic outcome at 6 month clinical follow-up.