Glycoprotein IIb/IIIa Receptor Inhibitors Research Articles

One-Year Outcome of Glycoprotein IIb/IIIa Inhibitor Therapy in Patients with Myocardial Infarction-Related Cardiogenic Shock.

Background: We aimed to evaluate the effect of intravenous glycoprotein IIb/IIIa receptor inhibitors (GPIs) on in-hospital survival and mortality during and at the 1-year follow-up in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) complicated by cardiogenic shock (CS), who were included in the Polish Registry of Acute Coronary Syndromes (PL-ACS). Methods: From 2003 to 2019, 466,566 MI patients were included in the PL-ACS registry. A total of 10,193 patients with CS received PCI on admission. Among them, GPIs were used in 3934 patients. Results: The patients treated with GPIs were younger, had lower systolic blood pressure on admission, required inotropes and intra-aortic balloon pump (IABP) support more frequently, and showed a lower efficacy of coronary angioplasty. In both groups, the same rates of in-hospital adverse events were observed. A lower mortality rate was reported in the group treated with GPIs 12 months after admission (54.9% vs. 57.9%, p = 0.002). Therapy with GPI was an independent factor reducing the risk of mortality in the 12-month follow-up. Conclusions: The addition of GPIs to the standard pharmacotherapy combined with PCI in patients with MI and CS on admission reduced the risk of death in the 12-month follow-up period without increasing in-hospital adverse event rates.

Meta-analysis of bivalirudin versus heparin in transradial coronary interventions.

We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI). Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results. A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding. We identified 10 RCTs, including 16,328 patients who underwent TRI (mean age 64.6 ± 15.7 years, 72.5% male). Bivalirudin use was associated with decreased 30-day NACE compared with heparin (6.3 vs. 7.4%; risk ratio [RR] = 0.87; 95% confidence interval [CI] = 0.76-0.99; p = .04; number needed to treat = 91). No significant interactions were observed based on clinical presentation, administration of P2Y12 inhibitors, or glycoprotein IIb/IIIa-receptor inhibitors (GPI) use. There were no significant differences between groups in any prespecified secondary outcomes. There was, however, a significant reduction of major bleeding in the bivalirudin group compared with heparin when used in combination with routine GPI (RR = 0.41; 95% CI = 0.19-0.90; p = .03). Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin.

Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use.

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y12 inhibitors. Cangrelor is an intravenous P2Y12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.

The association of the coronary thrombus burden with all-cause mortality and major cardiac events in ST-segment elevation myocardial infarction patients treated with tirofiban.

The aim of this study was to investigate the association of the coronary thrombus burden with all-cause mortality and major adverse cardiac events (MACE) in ST-segment elevation myocardial infarction (STEMI) patients treated with 'in-cath lab' (downstream) high-dose bolus tirofiban. This study included 2452 patients with STEMI treated with a primary percutaneous coronary intervention. All glycoprotein IIb/IIIa receptor inhibitor (GPI) (tirofiban) infusions were started in the catheterization laboratory according to the coronary thrombus burden; tirofiban was not administered to patients who did not have coronary thrombus burden. All patients with small, moderate, or large thrombus burden received tirofiban therapy. The primary study endpoint was the incidence of all-cause mortality. The secondary study endpoints were major bleeding and MACE, which included all-cause death, nonfatal acute coronary syndrome, and target lesion revascularization. The patients were followed up for a mean period of 28.3±10.4 months. The groups showed similar in-hospital and long-term event rates (MACE, major bleeding, and all-cause mortality). The 3-year Kaplan-Meier overall survivals for no thrombus, small thrombus, moderate thrombus, and large thrombus were 91.9, 92.6, 92.3, and 89.5%, respectively. Despite the fact that the large coronary thrombus was found to be a predictor of MACE and mortality in many previous studies, we found that the large thrombus was not associated with MACE or in-hospital mortality or long-term mortality. This can be an effect of downstream GPI therapy. We suggest the use of downstream GPI therapy for STEMI patients with large coronary thrombus without an increased risk of bleeding.

Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review.

Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.

Pretreatment with antiplatelet drugs in invasively managed patients with coronary artery disease in the contemporary era: review of the evidence and practice guidelines.

Antiplatelet therapy is the mainstay of pharmacological management in patients with coronary artery disease (CAD) manifestations, particularly those with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).1 In these settings, platelet inhibition with aspirin and a P2Y12 receptor inhibitor is associated with ischemic benefit, although this may occur at the expenses of an increased risk of bleeding.2–4 Clopidogrel is the most studied P2Y12 receptor and still represents the most used across the globe. However, a major conundrum in clinical practice, which has been amplified during the recent years with the development of novel antiplatelet therapies, both oral (prasugrel and ticagrelor) and intravenous (cangrelor), is whether patients undergoing an invasive evaluation should be pretreated with a P2Y12 receptor inhibitor.5 The introduction of novel antiplatelet therapies has also led to question the role of pretreatment with glycoprotein IIb/IIIa receptor inhibitors (GPI).6 Although the need for adequate platelet inhibition is emphasized among invasively managed patients with CAD, the evidence supporting pretreatment, particularly with P2Y12 inhibitors, is somewhat scarce. Indeed, changes in practice patterns in the current era of ACS management, which is typically characterized by shorter timeframes from clinical presentation to the cath-laboratory, have fueled the debate on the benefits of pretreatment. On one side, proponents of pretreatment call into question the need for safeguarding the patient from ischemic events in the early vulnerable period before and immediately after PCI.7 On the other side, challengers of pretreatment raise concerns over the putative unnecessary excess of platelet inhibition and related bleeding risk when patients do not undergo PCI (ie, when medical management or coronary artery bypass grafting [CABG] is needed).8 Overall, in view of the conflicting data and the newly available studies exploring the effect of pretreatment with antiplatelet …

TCTAP A-132 Impact of Periprocedural Glycoprotein IIbIIIa Receptor Inhibitors on TIMI Flow and 1 Month Major Clinical Outcomes Following Primary Percutaneous Coronary Intervention in Diabetic Patients

TCTAP A-132 Impact of Periprocedural Glycoprotein IIbIIIa Receptor Inhibitors on TIMI Flow and 1 Month Major Clinical Outcomes Following Primary Percutaneous Coronary Intervention in Diabetic Patients

Impact of baseline hemorrhagic risk on the benefit of bivalirudin versus unfractionated heparin in patients treated with coronary angioplasty: A meta-regression analysis of randomized trials

Bivalirudin significantly reduces 30-day major and minor bleeding compared with unfractionated heparin (UFH), while resulting in similar or lower rates of ischemic events in both patients with stable and unstable coronary disease undergoing percutaneous coronary intervention. We performed a meta-analysis of randomized trials to evaluate the impact of bivalirudin compared with UFH, with or without glycoprotein IIb/IIIa receptor inhibitors (GPI), on the rates of mortality, myocardial infarction (MI), and major bleeding. We searched electronic databases for randomized controlled trials with >100 patients comparing bivalirudin (±provisional GPI) with UFH with either routine or provisional GPI in patients undergoing percutaneous coronary intervention. The principal efficacy end points were mortality and MI within 30 day, whereas major bleeding was the principal safety end point. We assessed the benefit of bivalirudin for each efficacy end point relative to the baseline bleeding risk, using the control (UFH) major bleeding rate as proxy for that risk. A total of 12 randomized trials that enrolled 33,261 patients were included. Overall, there was no significant difference in mortality and MI between bivalirudin monotherapy and UFH (±GPI), whereas major bleeding was significantly lower with bivalirudin. Bivalirudin reduced major and minor bleeding across the entire bleeding risk spectrum. Bivalirudin significantly reduces major and minor bleeding regardless of the estimated baseline hemorrhagic risk.

Efficacy and safety of tirofiban-supported primary percutaneous coronary intervention in patients pretreated with 600 mg clopidogrel: results of propensity analysis using the Clinical Center of Serbia STEMI Register

Studies with platelet glycoprotein IIb/IIIa receptor inhibitors (GPIs) showed conflicting results in primary percutaneous coronary intervention (PPCI) patients who were pretreated with 600 mg clopidogrel. We sought to investigate the short- and long-term efficacy and safety of the periprocedural administration of tirofiban in a largest Serbian PPCI centre. We analysed 2995 consecutive PPCI patients enrolled in the Clinical Center of Serbia STEMI Register, between February 2007 and March 2012. All patients were pretreated with 600 mg clopidogrel and 300 mg aspirin. Major adverse cardiovascular events, comprising all-cause death, nonfatal infarction, nonfatal stroke, and ischaemia-driven target vessel revascularization, was the primary efficacy end point. TIMI major bleeding was the key safety end point. Analyses drawn from the propensity-matched sample showed improved primary efficacy end point in the tirofiban group at 30-day (OR 0.72, 95% CI 0.53-0.97) and at 1-year (OR 0.74, 95% CI 0.57-0.96) follow up. Moreover, tirofiban group had a significantly lower 30-day all-cause mortality (secondary end point; OR 0.63, 95% CI 0.40-0.90), compared with patients who were not administered tirofiban. At 1 year, a trend towards a lower all-cause mortality was observed in the tirofiban group (OR 0.74, 95% CI 0.53-1.04). No differences were found with respect to the TIMI major bleeding during the follow-up period. Tirofiban administered with PPCI, following 600 mg clopidogrel pretreatment, improved primary efficacy outcome at 30 days and at 1 year follow up without an increase in major bleeding.

Comparative effectiveness of upstream glycoprotein IIb/IIIa inhibitors in patients with moderate- and high-risk acute coronary syndromes: An Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) substudy

Tirofiban and eptifibatide are both small-molecule, competitive glycoprotein IIb/IIIa receptor inhibitors (GPIs) that are guideline-supported for upstream therapy in acute coronary syndromes (ACS). This study sought to compare the efficacy and safety of tirofiban and eptifibatide in patients with ACS. Within the ACUITY trial, 4,323 patients with moderate- and high-risk ACS received upstream, adjunctive GPI (tirofiban or eptifibatide) in addition to an antithrombin. Primary outcomes included 30-day rates of composite major adverse cardiac events (MACE), major bleeding (not related to coronary artery bypass grafting), and composite net adverse clinical events (NACE). The outcomes were compared based on the upstream GPI administered. There were significant differences in the baseline characteristics of patients treated with tirofiban vs eptifibatide, particularly related to country/region. In unadjusted analyses, treatment with upstream tirofiban vs eptifibatide was associated with similar rates of major bleeding (5.8% vs 6.5%, P = .39) and nonsignificantly lower rates of MACE (6.1% vs 7.6%, P = .06) and NACE (10.6% vs 12.6%, P = .06). After propensity-based multivariable adjustment, there were no significant differences between tirofiban and eptifibatide with respect to 30-day major bleeding, MACE, or NACE. Among more than 4,000 patients with moderate- and high-risk ACS treated with upstream GPI as part of an early invasive management strategy, the use of tirofiban and eptifibatide resulted in similar clinical outcomes. These data suggest equivalence of these 2 agents for upstream use, while highlighting some of the difficulties of nonrandomized comparative effectiveness analyses, specifically the difficulty in addressing geographic differences in the use of nonrandomized treatments.

Safety and Efficacy of Adjuvant Glycoprotein IIb/IIIa Inhibitors During Primary Percutaneous Coronary Intervention Performed From the Radial Approach for Acute ST Segment Elevation Myocardial Infarction

The use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) in high-risk patients with acute coronary syndromes has been associated with reductions in ischemic events but increases in bleeding complications. The role of GPIs in patients who undergo primary percutaneous coronary intervention (PCI) by the transradial approach (TRA) is not well studied. The aim of this post hoc analysis from the randomized prospective Acute Myocardial Infarction Treated With Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up (ATOLL) trial was to assess the safety and efficacy of GPIs in primary PCI performed using the TRA. A total of 910 patients were enrolled in ATOLL; 522 patients (67%) underwent PCI using the TRA. Two comparative analyses were performed. First, patients who underwent PCI using the TRA who received GPIs were compared with those who did not receive GPIs. Second, patients who underwent PCI using the TRA who received GPIs were compared with those who underwent PCI using a nonradial route and received GPIs. Composite end points of net clinical benefit, ischemic outcomes, and safety consisting of bleeding and transfusion at 1 month were analyzed. A propensity score was constructed, and weight adjustment were made for variables, including but not limited to age, weight, gender, renal function, concomitant use of other medications, Killip class, and medical history, when analyzing the end points. There was no significant difference in net clinical benefit or ischemic outcomes between either TRA patients with versus without GPIs or TRA patients with GPIs versus non-TRA patients with GPIs. Additionally, there were significantly fewer major bleeding events and blood transfusions in TRA patients with GPIs compared with non-TRA patients with GPIs. In conclusion, the addition of GPIs in the setting of primary PCI using the TRA was not associated with bleeding liability. The use of GPIs with TRA was associated with safer outcomes than using GPIs with a nontransradial approach. This study was limited in that it was a nonrandomized retrospective analysis.

Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute ST-elevation myocardial infarction and cardiogenic shock

Although radial approach is increasingly used in percutaneous coronary interventions (PCIs) including in acute myocardial infarction (MI), patients with cardiogenic shock have been excluded from comparisons with femoral approach. The aim of our study was to compare clinical outcomes in patients undergoing primary PCI with cardiogenic shock by radial and femoral approach. From 2,663 patients presenting with ST-elevation MI in 2 large volume radial centers, we identified 197 patients (7.4%) with signs of cardiogenic shock immediately before undergoing primary PCI. Radial approach was used in 55% of cases when at least 1 radial artery was weakly palpable, either spontaneously or after intravenous noradrenaline bolus. Patients in the radial group were older (69 ± 12 vs 64 ± 12 years, P = .010), had less diabetes (13% vs 26%, P = .028), and required less often intubation prior PCI (42% vs 66%, P = .0006) or intraaortic balloon pump (36% vs 55%, P = .0096). Mortality at 1 year was 44% in the radial group and 64% in the femoral group (P = .0044). Independent predictors of late mortality included radial approach (hazard ratio [HR] 0.65, 95% CI 0.42-0.98, P = .041), the use of glycoprotein IIb-IIIa receptor inhibitors (HR 0.63, 95% CI 0.40-0.96, P = .032), baseline creatinine ≥110 μmol/L (HR 3.34, 95% CI 2.20-5.12, P < .0001), initial glycemia >200 mg/dL (HR 2.02, 95% CI 1.34-3.11, P = .0008), and age >65 years (HR 1.80, 95% CI 1.18-2.79, P = .006). Radial approach was safe and feasible in more than half of the patients with ST-elevation MI and cardiogenic shock treated by primary PCI. After adjustment for baseline and procedural characteristics, radial approach remained associated with better survival. However, prognosis of patients undergoing primary PCI in cardiogenic shock remains poor.

Antiplatelet and antithrombin strategies in acute coronary syndrome: state-of-the-art review.

Antiplatelet and antithrombotic agents significantly alter the clinical course of patients with acute coronary syndrome (ACS) and hence form the bedrock of the management pathway of this closely related continuum of coronary pathologies. The contemporary therapeutic armamentarium for the treatment of ACS now reflects the many technical and pharmacological advances that took place over the last two decades. In the original 1996 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of acute myocardial infarction, only one antiplatelet agent (Aspirin) and one anticoagulant (unfractionated heparin) were recommended as class I therapies. Since then many newer agents have been developed and approved for routine clinical use in ACS patients. Recent research has focussed on improving efficacy on one hand and reducing bleeding complications on the other. This review focuses on the mechanism, efficacy, safety profile and clinical trial evidence of P2 Y12 receptor antagonist antiplatelet agents, glycoprotein IIb/IIIa receptor inhibitors (GPI), protease-activated receptor-1 (PAR-1) inhibitors, thrombin inhibitor bivalirudin and Factor Xa inhibitors fondaparinaux and rivaroxaban.

Abstract 4017: Safety of Intra-Arterial Bolus and Intravenous Infusion of Eptifibatide as an Adjunct to Intravenous Alteplase in Acute Ischemic Stroke: A Prospective Registry

Background and Purpose: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity for platelet glycoprotein IIb-IIIa receptors and a short half-life, has been shown to reduce the risk of ischemic events associated with coronary interventions. However, its role in conjunction with full dose intravenous alteplase in neurointerventional procedures needs to be determined. We report the results of an open-label prospective registry to evaluate the safety (in terms of avoiding hemorrhagic complications) and effectiveness (in terms of recannalization rates and clinical improvement) of administering eptifibatide. Method: Patients data was prospectively maintained at a University-affiliated community hospital from January 2010 to June 2011. Consecutive patients with moderate to severe stroke who received intravenous Alteplase and failed to improve were studied. Femoral artery access was established and site of cerebral occlusion crossed with microcatheter. Each patient was administered 135 mcg/kg intraarterial bolus followed by intravenous eptifibatide infusion (0.5-microg/kg/min) for 20 hours. The outcome analysis was done to look at recannalization rates, clinical improvement within 24 hours and mRS at discharge. The primary safety end point was symptomatic intracranial or major extra-cranial bleeding. Result: Sixteen patients (Mean Age 72.7, Range 30-93, Male-5(31.25%), Female-11(68.75%)) underwent treatment with this strategy. Recannalization was achieved in 93.75%(n=16)(Complete Recannalization in 43.75%, Partial Recannalization in 50%). There was immediate clinical improvement in 68.75% and good outcomes in 31.25%. One symptomatic and one asymptomatic intracerebral hemorrhage occurred during the follow-up period. Minor femoral site bleeding without requiring transfusion occurred in one patient. Conclusions: In conclusion, eptifibatide administered as an adjunct to thrombectomy for bridging after intravenous Alteplase appears to be safe and promotes recannalization in patients with acute ischemic stroke. Further studies are required to analyze eptifibatide efficacy after intravenous alteplase and its role in neurointerventional procedures.

Meta-Analysis of Randomized Controlled Trials Comparing Intracoronary and Intravenous Administration of Glycoprotein IIb/IIIa Inhibitors in Patients With ST-Elevation Myocardial Infarction

Glycoprotein IIb/IIIa receptor inhibitors (GPIs) have been widely adopted as an adjuvant regimen during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction, but whether intracoronary administration of these potent antiplatelet agents conveys better efficacy and safety over the intravenous route has not been well addressed. A meta-analysis was performed by a systematic search of the published research for randomized controlled trials comparing intracoronary versus intravenous administration of GPIs in patients with ST-segment elevation myocardial infarction. Eight studies involving 686 patients in the intracoronary arm and 660 in the intravenous arm met the inclusion criteria. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.08 to 1.98, p <0.05) and myocardial reperfusion grade 2 or 3 (OR 1.78, 95% CI 1.29 to 2.46, p <0.001) were markedly more often achieved in patients who received intracoronary boluses of GPIs than those receiving the intravenous strategy. Intracoronary administration resulted in a reduced incidence of mortality (OR 0.44, 95% CI 0.21 to 0.92, p <0.05), target vessel revascularization (OR 0.53, 95% CI 0.29 to 0.99, p <0.05), and the composite end point of major adverse cardiac events (OR 0.48, 95% CI 0.31 to 0.76, p <0.005) at 30-day follow-up. No significant difference was found in terms of major or minor bleeding (OR 1.14, p = 0.71, and OR 0.86, p = 0.47 respectively). In conclusion, intracoronary administration of GPIs yielded favorable outcomes in postprocedural blood flow restoration and 30-day clinical prognosis in patients with ST-segment elevation myocardial infarction. The intracoronary use of GPIs can be recommended as a preferred regimen during primary percutaneous coronary intervention.

Intra-Arterial Tirofiban Infusion for Partial Recanalization with Stagnant Flow in Hyperacute Cerebral Ischemic Stroke

Early reocclusion is a major concern associated with poor clinical outcomes in patients with an ischemic cerebral stroke. This occurs most frequently in patients with partial initial recanalization. This study focuses on partial recanalization with stagnant antegrade flow after intravenous (IV) tPA or spontaneously, treated with the administration of intra-arterial (IA) tirofiban. Three patients with initial M1 occlusion on diagnostic studies had an occluded segment that was recanalized with stagnant flow after IV tPA or spontaneously. In all cases, IA tirofiban was administrated. We evaluated the distal blood flow and the degree of vascular narrowing in the pre and post-procedure angiography and at follow-up in addition to the clinical status. In all patients, severe vascular narrowing with stagnation of blood flow was detected in the initial M1. After infusion of IA tirofiban, improvement of the distal blood flow was achieved rapidly within 40 minutes in all patients. The severe vascular narrowing resolved rapidly in two patients without residual stenosis. In one patient, moderate vascular narrowing was still present. The median baseline National Institutes of Health Stroke Scale (NIHSS) scores were 18 and the median post-procedural NIHSS scores were 2 at two weeks. No intracerebral hemorrhage occurred in any of the patients. Treatment with IA tirofiban was safe and effective in patients with partial initial recanalization. It can be suggested that detection of any partial recanalization is time for administration of glycoprotein IIb-IIIa receptor inhibitor in hyperacute ischemic stroke.

Bleeding Risk Comparing Targeted Low-Dose Heparin With Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

Prior randomized trials have shown reduced bleeding with bivalirudin compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). However, it is not known if this benefit is also present when UFH doses are more tightly controlled (as measured by activated clotting time, ACT). Patients enrolled in the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, were divided into 3 groups, based on the antithrombotic drug used during PCI (UFH monotherapy, UFH+glycoprotein IIb-IIIa receptor inhibitor [GPI], or bivalirudin alone). Propensity score matching was used to adjust for measured covariates (89 variables) and to compare bivalirudin versus UFH monotherapy and bivalirudin versus UFH+GPI groups. The UFH groups were stratified based on ACT achieved (optimal ACT defined as 250-300 for UFH monotherapy and 200-250 when GPI was also used). The primary bleeding outcome was in-hospital composite bleeding, defined as events of access site bleeding, Thrombolysis In Myocardial Infarction major/minor bleeding, or transfusion. Primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/MI/unplanned repeat revascularization at 12 months) were also evaluated. Propensity score matching yielded 3022 patients for the UFH monotherapy versus bivalirudin comparison and 3520 patients for the UFH+GPI versus bivalirudin comparison. Bivalirudin use was associated with numerically lower bleeding rates at all categories of achieved ACT when compared with UFH (low, optimal, high ACT: 2.5% versus 4.7%, 1.9% versus 6.0%, 3.1% versus 4.8%, respectively) or heparin+GPI groups (low, optimal, high ACT: 0.0% versus 2.7%, 2.7% versus 5.2%, 2.4% versus 6.1%, respectively) and was not associated with any statistically significant increase in either primary or secondary ischemic outcomes. Among unselected patients undergoing PCI, bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator ACT levels without an increase in ischemic outcomes.

Two hour bivalirudin infusion after PCI for ST elevation myocardial infarction

The standard of care for STEMI PCI for the past decade has been aspirin, clopidogrel, heparin, and a glycoprotein IIbIIIa receptor inhibitor (GPI). A bivalirudin strategy was shown to be superior to a GPI strategy in the HORIZONS AMI trial for net adverse clinical events (combined MACE and bleeding). An increased risk of acute stent thrombosis in the bivalirudin arm may have prevented broader adoption of bivalirudin for this indication. We hypothesized that acute stent thrombosis risk could be ameliorated by a 2 h infusion of bivalirudin following STEMI PCI. We implemented a multicenter, prospective registry for all STEMI patients in Vermont treated at a single PCI center. Each patient was routinely pre-loaded with dual antiplatelet therapy and 75% received an unfractionated heparin bolus prior to PCI. The utilization of bivalirudin bolus and continued 2 h infusion after PCI was routine with GPI bailout optional. 128 consecutive STEMI patients underwent primary PCI from October 1, 2008 to September 30, 2009. 92% of primary PCI patients received bivalrudin during and after the procedure with a 9% rate of bail out GPI. There was one case of probable or definite acute stent thrombosis (0.7%), and this single case occurred despite use of bailout GPI. Despite the prolonged infusion of bivalirudin, major bleeding occurred in only 1.7% of STEMI patients. In conclusion, prolonging bivalirudin for 2 h after STEMI PCI may be a promising method to alleviate acute stent thrombosis risk without losing the bleeding complication benefit of the bivalirudin strategy.

Antithrombotic therapy in patients with coronary artery disease and with type 2 diabetes mellitus

Diabetes mellitus (DM) is a life-threatening disease. Patients with DM have a 2- to 4-fold higher risk of developing cardiovascular disease compared to their non-diabetic counterparts. Several drugs are available for the treatment of stable coronary artery disease (CAD) and acute coronary syndrome (ACS). Among oral antiplatelet agents (acetylsalicylic acid, ticlopidine, clopidogrel, and prasugrel), prasugrel has shown the highest efficacy in patients with DM and ACS. The use of glycoprotein IIb-IIIa receptor inhibitors in diabetic subjects with ACS undergoing percutaneous coronary intervention (PCI) reduces adverse clinical events in a greater extent than in non-diabetics. Several direct and indirect antithrombins are recommended for the treatment of ACS such as unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. Enoxaparin and bivalirudin have been shown to be superior to UFH among patients with ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) also in diabetic subgroup analyses.

Long-term Mortality After Primary Percutaneous Coronary Intervention for High-risk Myocardial Infarction

Primary percutaneous coronary intervention (PPCI) has evolved, including the introduction of stents and platelet glycoprotein IIb/IIIa receptor inhibitors (GPI). The effects of these changes and other variables on long-term survival for a single-centre service were studied. A prospective database of clinical and angiographic variables were kept for patients treated with PPCI in Waikato Hospital from 1996 to 2006 (n=527). This was analysed with long-term mortality data. Survival was recorded using Kaplan-Meier curves. Multivariate analysis of factors at presentation, including ethnicity was performed. 5, 8 & 10-year survival rates were 76.5% (n=274), 72.7% (n=125) & 71.0% (n=19) respectively. Increased stent (42.8% vs. 84.1%, p<0.001) and GPI (39.6% vs. 73.3%, p<0.001) use was seen between early and late stages of the study. Stent use was associated with greater 5-year survival (80.5% vs. 70.8%, p=0.02), but GPI use was not. Multivariate analysis showed stent use independently predicted reduced mortality. Age, Maori ethnicity, renal failure and cardiogenic shock predicted higher mortality. Survival after PPCI remains high long-term. Stent and GPI use significantly increased. Stent, but not GPI, use was associated with improved survival. Maori ethnicity was under-represented in the study and is associated with worse long-term outcomes after myocardial infarction (MI).