Use Of Glycoprotein Research Articles

Abstract 5489: Provisional (bail-out) Use versus Routine Use of Glycoprotein 2b/3a Blockers in Stemi: A Sub-analysis From the On-time 2 Trial

Background: In daily practice, in patients (pts) with acute ST-elevation myocardial infarction, glycoprotein 2b/3a blockers use is often limited to the provisional use in case of complications after PCI. However, it is unknown whether this strategy is of any value as compared to the routine use of these agents before PCI. Methods: The On-TIME 2 trial compared routine pre-hospital initiation of high dose Tirofiban (HDT) versus provisional use of HDT in a randomized placebo controlled design. Thrombotic bail-out use of study medication was pre-defined and part of the combined clinical end-point. Within the pts who received blinded bail-out treatment, we compared pts who were pre-treated with placebo and received bail-out HDT (Tirofiban bail-out) versus those who were pre-treated with HDT and received bail-out placebo (Placebo bail-out). Results: Blinded bail-out use of study medication was used in 24% (237/980) of pts, with a significant higher use in pts pre-treated with placebo (29% (140/492) versus 20% (97/488), p=0.002). The indication for bail-out use of study medication was mostly distal embolisation or no-reflow after PCI and did not differ between the groups (73.6% vs 75.3% p=NS). As expected, bail-out use of study medication was associated with more residual ST deviation (5.5±7.2 vs 3.7±4.8mm), larger infarct size (median (IQR): 1750 (674–3117) vs 948 (379–2278) IU), and worse outcome (MACE 12.2% vs 5.6%, p<0.01 for all comparisons) as compared to no-bail-out treatment, table . Conclusion: Routine pre-hospital treatment with HDT significantly reduced the use of blinded bail-out study medication. Bail-out study medication was associated with larger infarct size and poor outcome, especially in those pts pre-treated with placebo. Therefore, routine pre-treatment with HDT is preferred over provisional use of HDT in pts with STEMI. It is highly questioned whether provisional use of glycoprotein 2b3a blockers in case of complications after PCI is effective at all. Table

Pourquoi je n’abandonne pas la voie fémorale !

Since its introduction in 1989, the safety of transradial approach compared to the femoral approach is mainly due to reducing entry site complications, allowing early ambulation, but at the price of a higher rate of procedural failure, arterial occlusion and radiation for operators and patients. Nevertheless, these advantages can be minimized with a modern femoral approach requiring a 4-French catheter for diagnostic angiography and a low dose heparin, new antithrombotic drugs and a reasonable use of glycoprotein (GB)IIb-IIIa for angioplasty. The radial approach is the best way to go in hemorrhagic high-risk patients and the femoral approach is safer in complex procedures. The operator has to hold the two accesses and to know when to switch to another approach to minimize complications, procedure time, radiation and contrast use.

Design and rationale of the Evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) trial

Currently recommended anticoagulant agents used in the setting of percutaneous coronary intervention (PCI) inhibit, with varying degrees of intensity, 2 critical targets (factor Xa and/or IIa) of the coagulation cascade, yet they carry significant limitations. M118-a novel, rationally engineered heparin-provides consistent anti-Xa and anti-IIa activity with a constant anti-Xa:anti-IIa ratio over time. M118 also combines the desired anticoagulant effects of unfractionated heparin with the beneficial attributes of low-molecular-weight heparin, and may represent the next generation of heparin therapy in patients diagnosed with acute coronary syndrome. The EMINENCE trial is a prospective, randomized, open-label, multicenter phase 2 study that will evaluate the safety and feasibility of M118 as an anticoagulant versus unfractionated heparin in subjects with stable coronary artery disease undergoing PCI. The primary end point of the study will be the combined incidence of clinical events defined as the composite of 30-day death, myocardial infarction, repeat revascularization, catheter thrombus, stroke, thrombocytopenia, bailout use of glycoprotein IIb/IIIa inhibitors, and major or minor bleeding. The EMINENCE trial will assess the safety and feasibility of M118 as an anticoagulant in the setting of PCI and will provide important information to determine the appropriate therapeutic range of activated clotting time for M118 and the appropriate dose or doses to be explored in a phase 3 clinical trial.

TCT-313: A randomized Controlled Trial of Upstream versus Bail-out Use of Glycoprotein IIb/IIIa Inhibitor Combined with Selective Use of Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention in Patients with ST-segment Elevation Myocardial Infarction

TCT-313: A randomized Controlled Trial of Upstream versus Bail-out Use of Glycoprotein IIb/IIIa Inhibitor Combined with Selective Use of Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention in Patients with ST-segment Elevation Myocardial Infarction

Perfil demográfico e resultados imediatos dos pacientes submetidos a angioplastia primária no Registro SOLACI

FUNDAMENTO: A superioridade da angioplastia primária em relação aos fibrinolíticos já foi amplamente demonstrada em diversos estudos, mas, muitas vezes, por questões logísticas, observamos retardo na incorporação das recomendações nos diversos cenários de vida real. Comparamos o desempenho da angioplastia primária no Registro SOLACI em três períodos a partir de 1995. MÉTODO: O Registro SOLACI incluiu dados de 43.725 angioplastias primárias realizadas nos períodos de 1995-1997 (n = 6.793), 2000-2003 (n = 23.007) e 2007-2008 (n = 13.925). RESULTADOS: Observamos complexidade crescente dos pacientes tratados, com incremento do porcentual de mulheres, diabéticos, e pacientes com infarto agudo do miocárdio prévio e com disfunção ventricular moderada a grave. O sucesso do procedimento manteve-se elevado (> 91%) em todos os períodos, independentemente do instrumental utilizado. Adicionalmente, notamos diminuição expressiva do tempo porta-balão, uso crescente dos stents e redução de 45% na utilização dos inibidores da glicoproteína IIb/IIIa. No que tange à evolução hospitalar, em comparação ao período de 1995-1997, observamos, nos períodos de 20002003 e 2007-2008, decréscimo da mortalidade (9,1% vs. 5,3% e 4,5%) e redução do reinfarto (4,1% vs. 2,6% e 2,7%) e da necessidade urgente de nova revascularização (3,5% vs. 0,7% e 0,7%). CONCLUSÃO: Apesar do perfil de risco mais complexo, a incorporação dos avanços tecnológicos e a redução do tempo porta-balão resultaram em melhora dos desfechos cardíacos hospitalares pós-angioplastia primária na América Latina.

The expanded Global Registry of Acute Coronary Events: Baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes

The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort. We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS. From 2001 to 2007, 31,982 patients were enrolled at 184 hospitals in 25 countries; 30% were diagnosed with ST-segment elevation myocardial infarction, 31% with non-ST-segment myocardial infarction, 26% with unstable angina, and 12% with another cardiac/noncardiac final diagnosis. The median age was 65 (interquartile range 55-75) years; 24% were >75 years old, and 33% were women. In general, increases were observed over time across the spectrum of ACS (1) in the use in the first 24 hours and at discharge of aspirin, clopidogrel, beta-blockers, and angiotensin-converting enzyme inhibitors/receptor blockers; (2) in the use at discharge of statins; (3) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin; and (4) in the use of cardiac catheterization and percutaneous coronary intervention. An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infarction were also seen. Over the course of 7 years, general increases in the use of evidence-based therapies for ACS patients were observed in the expanded GRACE.

Antiplatelet therapy in percutaneous coronary intervention: A critical review of the 2007 AHA/ACC/SCAI guidelines and beyond

Antiplatelet therapy is a mainstay in the treatment of patients who have undergone percutaneous coronary intervention (PCI). Although the 2007 PCI treatment guidelines were published by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions, new clinical evidence has emerged, expanding our understanding of antiplatelet use and potentially affecting the treatment guidelines. For example, clinical trial results prompted a Science Advisory to recommend that dual therapy with aspirin and clopidogrel be used for longer periods-up to 1 year in patients who receive bare metal stents and at least 1 year in patients receiving drug-eluting stents. New trial results have also emerged regarding the use of glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban. This article reviews the current recommendations for antiplatelet therapy in PCI patients, recent trial results, newly developed agents, ongoing clinical trials, and the future direction of antiplatelet therapy in patients who undergo PCI.

Guidelines to Practice Gap in the Use of Glycoprotein IIb/IIIa Inhibitors: From ISAR‐REACT to Overreact?

Adjunctive use of glycoprotein IIb/IIIa inhibitors (GPI) is associated with favorable outcomes following percutaneous coronary intervention (PCI). Guidelines for use of GPI have been published by various national societies including National Institute of Clinical Excellence (NICE), United Kingdom. The latter has not been updated since publication. The impact of contemporary trials such as ISAR-REACT (which showed no benefit of abciximab and 600 mg of clopidogrel compared with 600 mg of clopidogrel alone, in elective patients) on adherence to NICE guidelines is unknown. We audited use of GPI against NICE guidelines following publication in May 2002. Data were collected from 1,685 patients between September and November in years 2002, 2003, 2004, and 2007. In 2002 and 2003, only 10.2% and 11.8%, respectively, of patients were noncompliant to NICE guidelines. Over time, there was an increase in patients not given GPI despite meeting NICE criteria. After publication of ISAR-REACT, the comparative figures for noncompliance in 2004 and 2007 were 40.0% and 44.5%. A similar pattern was seen in patients with diabetes; in 2002 and 2003 noncompliance was 16.7% and 11.1%, respectively, and in 2004 and 2007 noncompliance was 38.0% and 44.7%, respectively. Qualitatively, similar findings were recorded in patients with NSTE-ACS. The overall noncompliance to NICE guidelines increased from 11.0% to 42.1% (P < 0.0001) after the ISAR-REACT study. We found a decline in compliance to NICE guidelines on GPI usage during PCI. This was likely influenced by contemporary trials demonstrating little or no benefit of GPI in patients undergoing elective PCI who are adequately pretreated with clopidogrel. Our findings suggest the need for a mechanism whereby regular updates to guidelines can be disseminated following new trial evidence.

Antiplatelet Agents in the Perioperative Period

To determine the use of the 3 major classes of antiplatelet drugs (aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors), their management in the perioperative period, and the risks associated with premature withdrawal. We reviewed the PubMed, EMBASE, and Cochrane databases using the terms antiplatelet agents in the perioperative period, antiplatelet agents and management of bleeding, drug-eluting stents and stent thrombosis, substitutes for antiplatelet agents, and premature withdrawal of antiplatelet agents. Randomized, double-blind, placebo-controlled trials; prospective observational studies; review articles; clinical registry data; and guidelines of professional bodies pertaining to antiplatelet agents were included. Two researchers independently read the selected abstracts and selected the studies that matched the inclusion criteria. Any discordance between the 2 researchers was resolved by discussion so that 99 articles were finally included. Aspirin use should not be stopped in the perioperative period unless the risk of bleeding exceeds the thrombotic risk from withholding the drug. With the exception of recent drug-eluting stent implantation, clopidogrel bisulfate use should be stopped at least 5 days prior to most elective surgery. Use of glycoprotein IIb/IIIa inhibitors must be discontinued preoperatively for more than 12 hours to allow normal hemostasis. Premature withdrawal of antiplatelet agents is associated with a 10% risk of all vascular events. Following drug-eluting stent implantation, withdrawal is associated with stent thrombosis and potentially fatal consequences. No definitive guidelines exist to manage patients who are actively bleeding while taking these drugs.

Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay

The clinical impact of platelet aggregation assessed by point-of-care assays is unknown. We sought to evaluate whether high residual platelet reactivity (RPR) to ADP during clopidogrel therapy, measured by a point-of-care assay, predicts adverse clinical events in acute coronary syndrome patients undergoing percutaneous coronary intervention. We used the VerifyNow P2Y12 assay (Accumetrics Inc, San Diego, Calif) to determine RPR to ADP in 683 patients with acute coronary syndrome undergoing dual-antiplatelet therapy who underwent percutaneous coronary intervention with bare-metal or drug-eluting stent implantation. All patients received a single 600-mg clopidogrel loading dose followed by 75 mg of clopidogrel daily and 100 to 325 mg of aspirin daily. The end points of the study at follow-up of 12 months were cardiovascular death, nonfatal myocardial infarction (MI), and target-vessel revascularization. At a 12-month follow-up, we found 51 ischemic events (24 cardiovascular deaths [3.5%], 27 nonfatal MIs [3.9%]) and 40 target-vessel revascularizations (5.8%). By receiver operating characteristic curve (ROC) analysis, the optimal cutoff value in predicting 12-month cardiovascular death and nonfatal MI was P2Y12 reaction unit values > or =240. RPR, defined in the presence of P2Y12 reaction unit values above this cutoff, was found to be a significant and independent predictor of cardiovascular death and nonfatal MI in a model that adjusted for cardiovascular risk factors, renal failure, reduced left ventricular ejection fraction, multivessel disease, total stent length, bifurcation lesions, number of lesions treated, type of stent, and use of glycoprotein IIb/IIIa inhibitors (cardiovascular death: hazard ratio 2.55, 95% CI 1.08 to 6.07, P=0.034; nonfatal MI: hazard ratio 3.36, 95% CI 1.49 to 7.58, P=0.004). No significant association was found between high RPR and the risk of target-vessel revascularization. RPR to ADP with clopidogrel therapy, measured by the point-of-care assay VerifyNow P2Y12, is able to detect acute coronary syndrome patients at risk of 12-month cardiovascular death and nonfatal MI. The optimal cutoff value was identified as being 240 P2Y12 reaction units.

Drug-Eluting or Bare-Metal Stents for ST Elevation Myocardial Infarction Can Observational Data Balance the Risk Benefit Equation?

The randomized clinical trials leading to initial approval of drug-eluting stents (DES) by the United States Food and Drug Administration were conducted by design in a homogeneous group of lower risk patients with mostly noncomplex coronary lesions.1,2 These studies demonstrated a clear benefit in the reduction of restenosis without any evidence of a safety concern during 1 year follow-up. Shortly after approval of the sirolimus and paclitaxel-eluting stents, safety and effectiveness was reported from small nonrandomized studies in a variety of more complex patient and lesion subgroups and resulted in a large proportion of so-called off-label usage.3,4 Article see p 176 Increased concern over the safety of acute DES implantation during primary percutaneous coronary intervention for ST elevation myocardial infarction (MI) left this indication as one of the last to gain widespread usage in favor of bare-metal stents (BMS). A study from Rotterdam comparing 186 consecutive patients receiving a DES from April 2002 to January 2003 with 183 patients receiving a BMS during an immediately preceding time interval demonstrated no increase in subacute stent thrombosis (0% versus 1.6%, P =0.10) and a significantly lower risk for major adverse cardiac events at 300 days (9.4% versus 17.0%, P =0.02) due to a markedly lower risk for target lesion revascularization (TLR) (1.1% versus 8.2%, P 80% penetration of DES among all percutaneous coronary intervention procedures by early 2006.6 Two small randomized trials of DES versus BMS conducted in Europe and published in September 2006, also showed no increase in stent thrombosis for DES within 1 year.7,8 In the summer of 2006, there were new concerns regarding late safety of DES with …

Coronary no‐reflow phenomenon: From the experimental laboratory to the cardiac catheterization laboratory

Coronary no-reflow occurs commonly during acute percutaneous coronary intervention, particularly in patients with acute myocardial infarction and those with degenerated vein grafts. It is associated with a guarded prognosis, and thus needs to be recognized and treated promptly. The pathophysiology originates during the ischemic phase and is characterized by localized and diffuse capillary swelling and arteriolar endothelial dysfunction. In addition, leukocytes become activated and are attracted to the lumen of the capillaries, exhibit diapedesis and may contribute to cellular and intracellular edema and clogging of vessels. At the moment of perfusion, the sudden rush of leukocytes and distal atheroemboli further contributes to impaired tissue perfusion. Shortening the door-to-balloon time, use of glycoprotein IIb/IIIa platelet receptor inhibitors and distal protection devices are predicted to limit the development of no-reflow during percutaneous interventions. Distal intracoronary injection of verapamil, nicardipine, adenosine, and nitroprusside may improve coronary flow in the majority of patients. Hemodynamic support of the patient may be needed in some cases until coronary flow improves.

Percutaneous coronary intervention and the use of glycoprotein IIb/IIIa inhibitors in patients with chronic kidney disease on dialysis: A single center experience

Patients on dialysis constitute a major healthcare burden with high prevalence of coronary artery disease frequently requiring coronary revascularization. Prior studies have reported high complications rates with revascularization in patients on dialysis. However, information on the use glycoprotein and direct thrombin inhibitors in this patient population undergoing percutaneous revascularization is limited. We retrospectively analyzed the procedural success and in-hospital outcomes of percutaneous coronary revascularization in 56 consecutive patients on dialysis compared with 524 patients without renal failure, between January 2001 and August 2007 at our facility. Additionally, we also analyzed the off-label use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors during revascularization in this high-risk group of patients to evaluate for possible increased bleeding complications. In the study group, 7 interventions were performed on peritoneal dialysis and 49 on hemodialysis patients. Sixty-one percent of these patients had diabetes mellitus. A total of 72 lesions were intervened upon; 12 underwent angioplasty and 60 underwent stenting. Four of 72 interventions were not successful, giving a procedural success rate of 94%. There were 6 immediate complications (10.7%), but no deaths. Thirty-two patients (57%) received GP IIb/IIIa inhibitors while direct thrombin inhibitors were used during percutaneous coronary intervention in 11(20%) patients. There were no bleeding complications with use of either GP IIb/IIIa inhibitors or direct thrombin inhibitors. In our experience, percutaneous coronary intervention has high procedural success in dialysis patients and concomitant use of GP IIb/IIIa inhibitors is not associated with any major bleeding complications, making this a feasible, safe and effective revascularization option for patients on dialysis; however, this merits further study in a randomized prospective trial.

Risks and Benefits of Antiplatelet Therapy in Uremic Patients

Patients with renal insufficiency are at an increased risk for cardiovascular morbidity and mortality. Despite being at a substantial risk for thrombotic events, patients with renal insufficiency also experience a greater number of hemorrhagic complications associated with antiplatelet therapy than individuals with normal renal function. This review focuses on the benefits and risks of antiplatelet therapy in patients with impaired kidney function suffering from an acute coronary syndrome.

Relation of Left Ventricular Infarct Transmurality and Infarct Size After Primary Percutaneous Coronary Angioplasty to Time from Symptom Onset to Balloon Inflation

This study was performed to evaluate the impact of time to reperfusion on infarct size and transmurality after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In 73 patients undergoing primary PCI for STEMI, contrast-enhanced magnetic resonance imaging was performed. Infarct size and transmurality on delayed-enhancement imaging were measured. Infarct size was not associated with symptom onset-to-balloon time (23 +/- 9% for <180 minutes, 22 +/- 9% for 180 to 360 minutes, and 24 +/- 11% for >360 minutes, p = 0.62) or door-to-balloon time (23 +/- 8% for <90 minutes, 23 +/- 10% for 90 to 120 minutes, and 22 +/- 11% for >120 minutes, p = 0.88). Infarct transmurality increased significantly with a delay of symptom onset-to-balloon time (73 +/- 22% for <180 minutes, 78 +/- 14% for 180 to 360 minutes, and 86 +/- 14% for >360 minutes, p = 0.04), but not for door-to-balloon time (79 +/- 15% for <90 minutes, 76 +/- 19% for 90 to 120 minutes, and 81 +/- 18% for >120 minutes, p = 0.62). In multivariate analysis, anterior infarction (odds ratio 4.15, 95% confidence interval 1.31 to 13.18, p = 0.02) and myocardial blush grade 0/1 (odds ratio [OR] 3.89, 95% confidence interval [CI] 1.13 to 13.51, p = 0.03) independently predicted a large infarct (infarct size > or =25%). Symptom onset-to-balloon time (OR per 30 minutes 1.26, 95% CI 1.04 to 1.53, p = 0.02) was an independent predictor of transmural infarct (average transmural extent > or =75%) and use of glycoprotein IIb/IIIa inhibitors showed a protective effect (OR 0.09, 95% CI 0.02 to 0.53, p = 0.007). In conclusion, symptom onset-to-balloon time was significantly associated with infarct transmurality but not infarct size in patients undergoing primary PCI for STEMI.

High-risk Acute Coronary Syndrome Patients with Non-ST-Elevation Myocardial Infarction: Definition and Treatment

Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care. Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy. The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.

Development of Real-Time Polymerase Chain Reaction Assays for Rapid Detection and Differentiation of Wild-Type Pseudorabies and Gene-Deleted Vaccine Viruses

The successful eradication of pseudorabies in U.S. domestic swine was accomplished through the use of glycoprotein E (gE) deleted modified live virus vaccines and an accompanying gE differential enzyme-linked immunosorbent assay (ELISA). Yet, pseudorabies virus (PRV) was established in feral swine in the United States, becoming a potential reservoir of PRV for infection of domestic swine and other native wildlife. A critical need for the current PRV surveillance program in the United States is the rapid detection of PRV infection. For this reason, a set of 2 real-time polymerase chain reaction (PCR) assays by using TaqMan chemistry was developed and evaluated for their capability in the detection and differentiation of field and vaccine strains of PRV. PCR primers and probes were designed for gB and gE genes of PRV, respectively. The newly developed PRV-specific real-time PCR assays could detect all wild-type PRV isolates from diagnostic submissions and differentiate them from vaccine strains. The analytical sensitivity of the assays was approximately 0.1 plaque-forming units per reaction. The assays were highly specific for PRV, because no positive results were obtained from testing other common swine viral pathogens and other animal herpesviruses. The results of testing samples from domestic and feral swine and from bovine showed that the real-time PCR assays are more sensitive than gel-based PCR. These results demonstrated the potential application of the developed real-time PCR assays as a differential test for rapid and specific detection of PRV in domestic and feral swine, as well as nonporcine species that can be infected with PRV and serve as carriers.

The Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial: Study design and rationale

Advances in coronary angioplasty and adjunct pharmacology have improved patient outcomes after primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI). However, several areas for improvement remain. Hemorrhagic complications, which are common in patients receiving intense anticoagulant and antiplatelet agents during primary PCI to suppress ischemia, have been strongly associated with early and late mortality. Moreover, restenosis after bare-metal stents (BMSs) frequently results in symptom recurrence and the need for repeat rehospitalization and revascularization procedures. Newer pharmacologic agents and drug-eluting stents may address both of these issues. In the HORIZONS-AMI trial, 3,602 patients with AMI undergoing primary PCI were prospectively randomized to unfractionated heparin plus routine use of glycoprotein (GP) IIb/IIIa inhibitors versus the direct thrombin inhibitor bivalirudin plus provisional use of GP IIb/IIIa inhibitors reserved for predefined thrombotic complications. In a second randomization, 3,011 eligible patients were randomly assigned to either a polymer-based paclitaxel-eluting stent or to an otherwise identical BMS. The study was powered for the assessment of sequential safety and efficacy end points for each specific randomization, with clinical end points assessed at 30 days, 1 year, and then annually for 5 years. The ongoing HORIZONS-AMI trial will determine whether bivalirudin monotherapy reduces bleeding complications and improves overall event-free survival compared with unfractionated heparin plus the routine use of GP IIb/IIIa inhibitors in patients undergoing primary PCI for AMI. Furthermore, this study will determine whether paclitaxel-eluting stents safely reduce rates of ischemic target lesion revascularization compared with BMSs in the setting of primary PCI.

Bivalirudin With Provisional Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Primary Angioplasty in the Setting of Cardiogenic Shock

In patients undergoing percutaneous coronary intervention (PCI), clinical trials have demonstrated that the use of bivalirudin with provisional glycoprotein IIb/IIIa inhibitors is not inferior to heparin with systematic glycoprotein IIb/IIIa inhibitors on major adverse cardiac events and is associated with lower rates of bleeding in various clinical settings. Patients with cardiogenic shock (CS), however, have been excluded from all pivotal trials. A retrospective analysis of 86 consecutive patients undergoing PCI for acute myocardial infarction complicated by CS in our center from April 2003 to September 2007 was performed. In-hospital death, major adverse cardiac events, and bleeding rates were compared in 37 patients who received bivalirudin with or without glycoprotein IIb/IIIa inhibitors and 49 patients who were treated with heparin and glycoprotein IIb/IIIa inhibitors as anticoagulation management. Baseline demographic, clinical, and biological characteristics were similar in the 2 groups. The in-hospital death rate was significantly lower in the bivalirudin group (5.4 vs 32.7%, p = 0.002). There were no differences in the rate of major hematoma between the bivalirudin group and the heparin group (3 vs 2.6%, p = 0.46). In conclusion, bivalirudin with provisional use of glycoprotein IIb/IIIa inhibitors appears to be a safe and effective anticoagualtion strategy in patients undergoing primary PCI for acute myocardial infarction complicated by CS.

Bivalirudin

Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation in the setting of invasive cardiology, particularly percutaneous coronary intervention (PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs, it undergoes predominant non-organ elimination (proteolysis), and has the shortest half-life (approximately 25 min). Its affinity for thrombin is intermediate between that of lepirudin (highest) and argatroban (lowest)--this helps explain why it interferes with functional clotting assays to an extent intermediate between that achieved by these two other DTIs. This effect is best known for the PT (INR)--higher affinity for thrombin corresponds to lower molar DTI requirements to prolong the APTT; in turn, lower concentrations required for APTT prolongation (and, presumably, in-vivo effect) result in reduced PT (INR) prolongation. Bivalirudin is primarily used for its first FDA-approved indication, namely anticoagulation during percutaneous transluminal coronary angioplasty ("balloon angioplasty"), the most frequent type of PCI. Bivalirudin is also indicated for PCI with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple" endpoint comprising a "triple" efficacy endpoint plus major bleeding - this approach anticipated the subsequent emphasis on strategies to improve clinical outcomes through bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use for acute coronary syndrome (especially employing PCI), we review also the studies of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including both HIT and non-HIT situations.