Autoimmune disorders of platelet function: systematic review of cases of acquired Glanzmann thrombasthenia and acquired delta storage pool disease.

Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbß3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immune-mediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.

Outcome of patients admitted with acute coronary syndrome on palliative treatment: insights from the nationwide AMIS Plus Registry 1997-2014.

OBJECTIVE: Compliance with guidelines is increasingly used to benchmark the quality of hospital care, however, very little is known on patients admitted with acute coronary syndromes (ACS) and treated palliatively. This study aimed to evaluate the baseline characteristics and outcomes of these patients. DESIGN: Prospective cohort study. SETTING: Eighty-two Swiss hospitals enrolled patients from 1997 to 2014. PARTICIPANTS: All patients with ACS enrolled in the AMIS Plus registry (n=45,091) were analysed according to three treatment groups: palliative treatment, defined as use of aspirin and analgesics only and no reperfusion; conservative treatment, defined as any treatment including antithrombotics or anticoagulants, heparins, P2Y12 inhibitors, GPIIb/IIIa but no pharmacological or mechanical reperfusion; and reperfusion treatment (thrombolysis and/or percutaneous coronary intervention during initial hospitalisation). The primary outcome measure was in-hospital mortality and the secondary measure was 1-year mortality. RESULTS: Of the patients, 1485 (3.3%) were palliatively treated, 11,119 (24.7%) were conservatively treated and 32,487 (72.0%) underwent reperfusion therapy. In 1997, 6% of all patients were treated palliatively and this continuously decreased to 2% in 2013. Baseline characteristics of palliative patients differed in comparison with conservatively treated and reperfusion patients in age, gender and comorbidities (all p<0.001). These patients had more in-hospital complications such as postadmission onset of cardiogenic shock (15.6% vs 5.2%; p<0.001), stroke (1.8% vs 0.8%; p=0.001) and a higher in-hospital mortality (25.8% vs 5.6%; p<0.001).The subgroup of patients followed 1 year after discharge (n=8316) had a higher rate of reinfarction (9.2% vs 3.4%; p=0.003) and mortality (14.0% vs 3.5%; p<0.001). CONCLUSIONS: Patients with ACS treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. While refraining from more active therapy may often constitute the most humane and appropriate approach, we think it is important to also evaluate these patients and include them in registries and outcome evaluations. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT01 305 785.

Rescue treatment of thromboembolic complications during endovascular treatment of cerebral aneurysms: a meta-analysis.

BACKGROUND AND PURPOSE: Intraprocedural thrombus formation during endovascular treatment of intracranial aneurysms is often treated with glycoprotein IIb/IIIa inhibitors and, in some instances, fibrinolytic therapy. We performed a meta-analysis evaluating the safety and efficacy of GP IIb/IIIa inhibitors compared with fibrinolysis. We also evaluated the safety and efficacy of abciximab, an irreversible inhibitor, compared with tirofiban and eptifibatide, reversible inhibitors of platelet function. MATERIALS AND METHODS: We performed a comprehensive literature search for studies on rescue therapy for intraprocedural thromboembolic complications with glycoprotein IIb/IIIa inhibitors or fibrinolysis during endovascular treatment of intracranial aneurysms. We studied rates of periprocedural stroke/hemorrhage, procedure-related morbidity and mortality, immediate arterial recanalization, and long-term good clinical outcome. Event rates were pooled across studies by using random-effects meta-analysis. RESULTS: Twenty-three studies with 516 patients were included. Patients receiving GP IIb/IIIa inhibitors had significantly lower perioperative morbidity from stroke/hemorrhage compared with those treated with fibrinolytics (11.0%; 95% CI, 7.0%-16.0% versus 29.0%; 95% CI, 13.0%-55.0%; P = .04) and were significantly less likely to have long-term morbidity (16.0%; 95% CI, 11.0%-21.0% versus 35.0%; 95% CI, 17.0%-58.0%; P = .04). There was a trend toward higher recanalization rates among patients treated with glycoprotein IIb/IIIa inhibitors compared with those treated with fibrinolytics (72.0%; 95% CI, 64.0%-78.0% versus 50.0%; 95% CI, 28.0%-73.0%; P = .08). Patients receiving tirofiban or eptifibatide had significantly higher recanalization rates compared with those treated with abciximab (83.0%; 95% CI, 68.0%-91.0% versus 66.0%; 95% CI, 58.0%-74.0%; P = .05). No difference in recanalization was seen in patients receiving intra-arterial (77.0%; 95% CI, 66.0%-85.0%) or intravenous GP IIb/IIIa inhibitors (70.0%; 95% CI, 57.0%-80.0%, P = .36). CONCLUSIONS: Rescue therapy with thrombolytic agents resulted in significantly more morbidity than rescue therapy with glycoprotein IIb/IIIa inhibitors. Tirofiban/eptifibatide resulted in significantly higher recanalization rates compared with abciximab.

[A high-volume single center experience of no-reflow post-percutaneous coronary intervention]. / Incidenza del no-reflow calcolata su oltre 19 000 angioplastiche primarie ed elettive in un singolo centro ad alto volume.

BACKGROUND: The no-reflow (NR) phenomenon is frequent in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, its real incidence and prognostic significance, so far derived from relatively small patient cohorts, remain poorly defined. METHODS: We have retrospectively analyzed 19 290 consecutive PCI performed at our hospital between January 1998 and November 2010. NR was defined as a TIMI flow ≤2 at the end of the PCI. RESULTS: In the 1257 patients with STEMI, NR occurred in 9.4% of cases and was more common when the left anterior descending coronary artery was the culprit vessel. STEMI-NR patients had longer ischemic times and more frequently multivessel disease. In the STEMI-NR group, glycoprotein IIb/IIIa inhibitors were used in 60.2%, nitroprusside in 39.6%, thrombus aspiration in 10.7% and adenosine in 8.7%. In the remaining 18033 patients without STEMI undergoing PCI, the NR phenomenon occurred only in 0.2% of cases. STEMI-NR patients had lower left ventricular ejection fraction at discharge (50.3 ± 7.2 vs 44.9 ± 8.4%; p<0.01) and showed higher rates of adverse events (death, non-fatal myocardial infarction, coronary revascularization, new hospital admission for heart failure: 67.8 vs 36.9%, p=0.001), death (25.4 vs 13.2%, p<0.01), myocardial infarction (13.6 vs 4.8%, p<0.01) and hospitalizations for heart failure (13.6 vs 4.8%, p<0.001). CONCLUSIONS: Our data, derived from a large cohort of patients from a single center, allow a more correct estimate of the occurrence and prognostic significance of NR. The NR phenomenon is more common in STEMI patients undergoing primary PCI and has an important negative prognostic value.

Bridging therapy after recent stent implantation: case report and review of data.

For patients requiring surgery within their first year following coronary stent placement, maximizing the prevention of stent thrombosis with antiplatelet therapy while minimizing the risk of intraoperative bleeding has become a management challenge for cardiologists, surgeons and anesthesiologists. In this manuscript, we describe a case of a patient who received three stents (two of which were drug-eluting) and 7 months later was bridged with intravenous eptifibatide, a short-acting glycoprotein (GP) IIb/IIIa inhibitor, for 3 days prior to bronchoscopy and cervical mediastinoscopy for a suspected lung cancer. We then review the current literature for data and guidelines describing the use of short-acting GP IIb/IIIa as bridge therapy. Finally, we provide recommendations, based on our experience combined with this review, for bridge therapy in the perioperative period for patients with recent coronary stents.

Triple antiplatelet therapy in acute coronary syndromes.

Heightened platelet activity plays a critical role in thrombus formation, which is central to acute coronary syndromes (ACS), including non-ST-segment elevation (NSTE)-ACS (comprising unstable angina pectoris and non-ST-segment elevation myocardial infarction [NSTEMI]) and ST-segment elevation myocardial infarction (STEMI), and has been implicated in poor clinical outcome. Platelets not only impact coronary thrombus but are major contributors to microcirculatory dysfunction and vascular inflammation. Efforts to inhibit platelet function, including antiplatelet therapy, are paramount to the management of ACS; thus, a growing recognition of the various pathways driving platelet activity has given rise to the need for multiple agents that impart complimentary mechanisms of action. While only inhibiting platelet activation will still allow for aggregation, i.e. the binding of glycoprotein (GP) IIb/IIIa receptors to fibrinogen, solely blocking aggregation may leave platelet-activating pathways free to sustain the production and release of various pro-inflammatory and pro-thrombotic compounds. The benefit of 'triple antiplatelet therapy', referring to the combination of aspirin, a thienopyridine or non-thienopyridine adenosine diphosphate (ADP)/P2Y12 receptor blocker and a GPIIb/IIIa inhibitor (GPI), has been demonstrated in patients with NSTE-ACS who ultimately undergo percutaneous coronary intervention (PCI) and are determined to be at an elevated risk for ischaemic events, and in patients undergoing primary PCI. It is therefore recommended by the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association. Furthermore, the rationale for adding a GPI, particularly in patients with STEMI, is backed by studies that have shown negligible effects of a 600 mg clopidogrel loading dose, despite being administered 4 hours prior to PCI. Moreover, it has been observed that the physiological state of STEMI may deem dual antiplatelet therapy ineffective, because during an acute event the absorption of clopidogrel may be impaired. Nonetheless, there is still considerable variability with respect to the use of triple antiplatelet therapy such as that documented in the Euro Heart Survey. The perception that the mortality benefit afforded by adding a GPI to dual oral antiplatelet therapy does not outweigh the risk is a likely factor. This may be fuelled by results of trials such as BRAVE-3, which, inconsistent with those for On-TIME 2, failed to prove the value of adding a GPI to dual oral antiplatelet therapy in patients with STEMI. Subsequent analyses have indeed demonstrated the positive benefit-risk ratio associated with adding a GPI and determined that the timing of GPI administration could have an impact on clinical outcome related to its impact on infarct size in patients with STEMI. Additionally, it has been presumed that a synergistic effect exists between P2Y12 inhibitors and GPIs. Triple antiplatelet therapy has a significant role to play in the management of patients with ACS managed with PCI. An understanding of patient risk status and timing of symptoms and bleeding risk is crucial to patient selection and ensuring that this therapy is optimized. Though no interaction has been noted in trials of newer, more potent antiplatelet agents, future studies are key to determining the role of this strategy in the era of these more potent agents.

A risk score to predict bleeding in patients with acute coronary syndromes.

OBJECTIVES: The aim of this study was to develop a practical risk score to predict the risk and implications of major bleeding in acute coronary syndromes (ACS). BACKGROUND: Hemorrhagic complications have been strongly linked with subsequent mortality in patients with ACS. METHODS: A total of 17,421 patients with ACS (including non-ST-segment elevation myocardial infarction [MI], ST-segment elevation MI, and biomarker negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model. RESULTS: Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had 6 independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non-ST-segment elevation MI, or ST-segment elevation MI) and 1 treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c-statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non-CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non-CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality. CONCLUSIONS: Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non-CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.

Prolonged infusion of eptifibatide as bridge therapy between bare-metal stent insertion and cardiovascular surgery: case report and review of the literature.

Dual antiplatelet therapy with aspirin and clopidogrel is the standard of care after coronary artery stent insertion. Clopidogrel, however, has been associated with an increased risk of bleeding if it is used before coronary artery bypass grafting (CABG), and current guidelines recommend that it be discontinued at least 5 days before surgery. Compared with dual antiplatelet therapy, single antiplatelet therapy or the combination of an antiplatelet agent and an anticoagulant is associated with an increased risk of subacute stent thrombosis. Management of patients who require semiurgent CABG after stent insertion presents a clinical challenge. Intravenous glycoprotein IIb-IIIa inhibitors provide antiplatelet coverage with a shorter duration of action; thus, in theory, they may be useful for these clinical situations. We describe a 47-year-old man who came to the emergency department with sudden-onset, retrosternal chest pain. An electrocardiogram confirmed a diagnosis of ST-segment elevation myocardial infarction. The patient underwent angioplasty and received a bare-metal stent. Because significant disease was revealed in other arteries, CABG was scheduled. Clopidogrel was discontinued in preparation for surgery, and the patient received an infusion of eptifibatide 2 microg/kg/minute as bridging therapy to surgery for a total of 9 days. No major hemorrhagic or clinically evident thrombotic complications occurred before or after the surgery. Eptifibatide may be safe and effective as bridging therapy for patients with intracoronary stents who require CABG.

Effect of anemia on hemorrhagic complications and mortality following percutaneous coronary intervention.

The relation across anemia, hemorrhagic complications, and mortality associated with percutaneous coronary intervention (PCI) is unclear. We reviewed the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221). Mortality was higher in anemic patients than in nonanemic patients at 30 days (0.9% vs 0.2%, p <0.0001), 6 months (2.6% vs 0.7%, p <0.0001), and 1 year (4.3% vs 1.5%, p <0.0001). There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days. Although anemic patients had higher mortality rates, proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients. In conclusion, anemic patients undergoing PCI have an increased risk of mortality and major bleeding, but not of ischemic events, and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade.

An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards.

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death. We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting. A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%). Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes. The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.

Treatment of aortocoronary graft lesions with graft-stents.

OBJECTIVE: Previous controlled trials do not indicate a superiority of the polytetrafluoroethylene membrane-covered stent graft compared with a conventional stent with respect to acute results, restenosis, or clinical event rates. We evaluated the outcome of stenting aortocoronary bypass grafts with polytetrafluoroethylene-covered stent. METHODS: The study included 64 patients who had 73 saphenous graft-stent implants. Clinical follow-up was obtained for a median of 6.2 months (1-9 months) for 54 patients. RESULTS: The mean age of the grafts was 9.2+/-6 years (2-14 years). Procedural success was achieved in 72 of 73 lesions (98.6%). One patient having an anterior Q-wave myocardial infarction died on the second day of procedure. Four patients (6.2%) sustained distal embolization and no reflow. No reflow was overcome after intracoronary administration of nitroglycerine and verapamil in two cases. At follow-up, stable angina pectoris had developed in 10 patients (18%), unstable angina pectoris in two patients (3.7%), acute myocardial infarction in two patients (3.7%), and cardiac death in one patient (1.8%). A total of 45 patients had a coronary angiogram at 6 months of follow-up or earlier, and restenosis at the target site was detected in eight of 53 lesions (15%). CONCLUSIONS: Saphenous graft lesions can be managed successfully with polytetrafluoroethylene-covered stents with acceptable long-term clinical outcome. Further and larger studies are needed to compare conventional stents, polytetrafluoroethylene-covered stents, drug eluting stents, and additional benefit of distal protection devices in these subgroups.

Emergency coronary artery bypass surgery for percutaneous coronary interventions: changes in the incidence, clinical characteristics, and indications from 1979 to 2003.

OBJECTIVES: The purpose of the current study was to evaluate the changes in incidence, clinical characteristics, and indications for emergency coronary artery bypass grafting (CABG) in patients undergoing percutaneous coronary intervention (PCI) from 1979 to 2003. BACKGROUND: Emergency CABG after PCI is associated with significant morbidity and mortality. METHODS: Data from 23,087 patients who underwent PCI at Mayo Clinic from 1979 to 2003 were analyzed. Patients were divided into three groups: the "pre-stent" era, 1979 to 1994 (n = 8,905); the "initial stent era," 1995 to 1999 (n = 7,605); and the "current stent era," 2000 to 2003 (n = 6,577). RESULTS: Although patients undergoing PCI in the recent time periods had more high-risk features, there was a significant decrease in the incidence of emergency CABG from 2.9% to 0.7% to 0.3% across the groups (p < 0.001). Patients requiring emergency surgery in the recent time periods had a higher prevalence of hypertension, prior revascularization, and left ventricular dysfunction (ejection fraction <40%), as well as more complex coronary lesions. Fewer patients in the current stent era had coronary artery dissections and abrupt vessel closure requiring emergency CABG. The in-hospital mortality rate for emergency CABG patients remains unchanged and ranges from 10% to 14%. CONCLUSIONS: The current study demonstrates that despite the increase in high-risk patients undergoing PCI, there has been a marked decrease in the incidence of patients requiring emergency CABG. However, the in-hospital mortality rate for those requiring emergency CABG remains high and unchanged.

Therapeutic expression of the platelet-specific integrin, alphaIIbbeta3, in a murine model for Glanzmann thrombasthenia.

Integrins mediate the adhesion of cells to each other and to the extracellular matrix during development, immunity, metastasis, thrombosis, and wound healing. Molecular defects in either the alpha- or beta-subunit can disrupt integrin synthesis, assembly, and/or binding to adhesive ligands. This is exemplified by the bleeding disorder, Glanzmann thrombasthenia (GT), where abnormalities of the platelet-specific integrin, alphaIIbbeta3, prevent platelet aggregation following vascular injury. We previously used a retrovirus vector containing a cDNA cassette encoding human integrin beta3 to restore integrin alphaIIbbeta3 on the surface of megakaryocytes derived from peripheral blood stem cells of GT patients. In the present study, bone marrow from beta3-deficient (beta3-/-) mice was transduced with the ITGbeta3-cassette to investigate whether the platelet progeny could establish hemostasis in vivo. A lentivirus transfer vector equipped with the human ITGA2B gene promoter confined transgene expression to the platelet lineage. Human beta3 formed a stable complex with murine alphaIIb, effectively restoring platelet function. Mice expressing significant levels of alphaIIbbeta3 on circulating platelets exhibited improved bleeding times. Intravenous immunoglobulin effectively diminished platelet clearance in animals that developed an antibody response to alphaIIbbeta3. These results indicate the feasibility of targeting platelets with genetic therapies for better management of patients with inherited bleeding disorders.

Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.

In patients with stable CAD, PCI can be considered a valuable initial mode of revascularization in all patients with objective large ischaemia in the presence of almost every lesion subset, with only one exception: chronic total occlusions that cannot be crossed. In early studies, there was a small survival advantage with CABG surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected left main stenosis. The use of drug-eluting stents might change this situation. Patients presenting with NSTE-ACS (UA or NSTEMI) have to be stratified first for their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety. In patients with STEMI, primary PCI should be the treatment of choice in patients presenting in a hospital with PCI facility and an experienced team. Patients with contra-indications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a 'heart attack centre' observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 h after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major-adverse-cardiac-event rates increase after thrombolysis, but appear to remain relatively stable after primary PCI. Within the first 3 h after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 h after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 h of chest pain to prevent stroke, and in patients presenting 3-12 h after the onset of chest pain, to salvage myocardium and also to prevent stroke. At the moment, there is no evidence to recommend facilitated PCI. Rescue PCI is recommended, if thrombolysis failed within 45-60 min after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 h and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve patients' outcome. If a PCI centre is not available within 24 h, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of 'maximal' medical therapy.

Percutaneous coronary intervention versus coronary artery bypass grafting in diabetic patients.

Revascularization with CABG or angioplasty in diabetic patients is associated with a less favor-able outcome. The value of early intervention will be assessed in the ongoing BARI 2D trial. It remains to be determined whether the widespread use of GP IIb/IIIa drugs and prolonged dual antiplatelet therapy in diabetic patients who receive stents, and possibly drug-eluting stents, will alter results significantly so that outcomes become comparable or even better than CABG (Fig. 3). It seems prudent to consider CABG with LIMA grafting in diabetic patients who have severe multi-vessel disease and to consider angioplasty in selected patients who have more discrete and less severe disease.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: results from the REPLACE-2 trial.

OBJECTIVES: The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. BACKGROUND: Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. METHODS: In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. RESULTS: Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). CONCLUSIONS: Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Optimal duration of eptifibatide infusion in percutaneous coronary intervention (an ESPRIT substudy).

Although randomized trials have clearly demonstrated the clinical efficacy with regimens of platelet glycoprotein IIb/IIIa antagonists that result in >80% inhibition of baseline platelet aggregation in percutaneous coronary intervention (PCI), there are no data available concerning the optimal duration of infusion of these agents. In an era when the length of hospitalization has a major impact on health care costs, the determination of the optimal duration of the infusion of these drugs after PCI is of great relevance. The investigators therefore sought to determine the optimal length of the infusion of eptifibatide after PCI by analyzing the outcomes of patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy trial who were randomized to treatment with eptifibatide.