Glycoprotein IIb/IIIa Inhibitors Research Articles

Comparing efficacy of receiving different dosages of eptifibatide in bleeding after percutaneous coronary intervention in patients with myocardial infarction.

BACKGROUNDAcute coronary syndrome (ACS) is a common condition that needs appropriate treatment like percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitors (GPI) like eptifibatide prevent procedural ischemic complications after PCI. Eptifibatide has increased the risk of bleeding complications, although it is effective in reducing mortality and morbidity. Eptifibatide is routinely used in bolus and infusion forms and the aim of this study is to evaluate the efficacy of bolus-only dose and bolus + infusion strategy for administrating eptifibatide in bleeding complications and consequences after PCI.METHODSThis randomized clinical trial was conducted on subjects who experienced PCI after incidence of myocardial infarction (MI). Patients were randomly divided into two groups who received bolus-only dose (n = 51) or bolus + infusion form of eptifibatide (n = 50). Then, PCI blood pressure, mean time duration of hemostasis after arterial sheath removal, laboratory data, need for blood transfusion, and presence of bleeding complications were evaluated. After 6 months, patients were followed for needs for additional coronary interventions.RESULTSThe mean age of participants was 61.68 ± 1.50 years. The prevalence of men was 70.29%. There was no significant difference in mean of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during hospitalization (P > 0.050). The mean time duration of hemostasis was 8.13 ± 0.45 minutes in the bolus-only group and 16.46 ± 0.71 minutes in the bolus + infusion group (P < 0.001). There was no significant difference in the hemoglobin (Hb) level, platelet count, white blood cell (WBC), blood urea nitrogen (BUN), and creatinine level (P > 0.050).CONCLUSIONThe results of this study suggested that bolus-only dose of eptifibatide before PCI could be able to decrease significantly bleeding complication and other clinical and cardiovascular outcomes.

Relationship between degree of heparin anticoagulation and clinical outcome in patients receiving potent P2Y12-inhibitors with no planned glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention in acute myocardial infarction: a VALIDATE-SWEDEHEART substudy.

Heparin is the preferred choice of anticoagulant in percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). An established dosage of heparin has not yet been determined, but treatment may be optimized through monitoring of activated clotting time (ACT). The aim of this study was to determine the relationship between heparin dose or ACT with a composite outcome of death, MI, or bleeding using data from the registry-based, randomized, controlled, and open-label VALIDATE-SWEDEHEART trial, although patients were not randomized to heparin dose in this substudy. Patients with MI undergoing PCI and receiving treatment with a potent P2Y12-inhibitor and anticoagulation with heparin, without the planned use of glycoprotein IIb/IIIa inhibitor (GPI), were enrolled in this substudy. The primary endpoint was a composite endpoint of death, MI, and bleeding at 30 days. The individual components and stent thrombosis were analysed separately. We divided patients into groups according to the initial dose of unfractionated heparin during PCI (<70 U/kg, 70-100 U/kg, and >100 U/kg) or ACT (ACT <250 s, 250-350 s, and >350 s) as well as investigating them as continuous variables in Cox proportional hazards models using univariable and multivariable analyses. No major differences were noted between heparin stratified in groups (P = 0.22) or heparin as a continuous variable in relation to the primary composite endpoint hazard ratio (HR) 1.0 confidence interval (CI) (0.99-1.01) for heparin dose/kg. No differences were found between ACT stratified in groups (P = 0.453) or ACT in seconds HR 1.0 CI (0.99-1.00) regarding the primary endpoint. The individual components of death, MI, major bleeding, and stent thrombosis were not significantly different across heparin doses or ACT levels either. We found no association between heparin dose or ACT levels and death, MI bleeding complications, or stent thrombosis. Therefore, there is no strong support for a specific heparin dose or mandatory ACT monitoring in patients treated with potent P2Y12-inhibitors with no planned GPI.

Comparison of Routine Versus Selective Glycoprotein IIb/IIIa Inhibitors Usage in Primary Percutaneous Coronary Intervention (from the British Cardiovascular Interventional Society)

The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in >75% and <25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p < 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 [95% confidence interval 0.83 to 0.93], p < 0.001), multivariable analysis (hazard ratio = 0.82 [0.77 to 0.88], p < 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.

Impact of right ventricular dysfunction on mortality in adults with cardiac arrest undergoing coronary angiogram

ObjectiveWe sought to identify the impact of echocardiographic right ventricular (RV) systolic dysfunction on mortality in adults with cardiac arrest (CA). MethodsThe study population included 147 adults hospitalized with CA who underwent both echocardiogram and coronary angiogram at an academic tertiary medical center. The primary outcome of interest was all-cause in-hospital mortality. ResultsOf the 147 patients studied, 20 (13.6%) had evidence of RV systolic dysfunction while 127 (86.4%) did not. Patients with RV dysfunction had higher rates of prior surgical and percutaneous coronary revascularization. They also had higher rates of mechanical ventilation, therapeutic hypothermia, vasopressor and inotrope use, and a trend towards higher rates of mechanical support. Coronary angiogram revealed higher rates of multivessel disease, right coronary artery intervention, and glycoprotein IIb–IIIa inhibitor use in those with RV dysfunction, alongside with lower echocardiographic left ventricular ejection fraction. In-hospital mortality rates were higher in adults with RV dysfunction compared to those without (55% vs 11%, p < 0.001). In multivariate analysis, RV dysfunction was the strongest independent predictor of higher mortality [odds ratio 4.71, 95% confidence interval 1.27–17.50]. ConclusionsIn this observational contemporary study, RV dysfunction was independently associated with higher mortality in adults with CA undergoing coronary angiogram. RV dysfunction may be useful for risk stratification and management in this high-mortality population.

Favorable effect of glycoprotein IIbIIIa inhibitors among STEMI patients treated with primary PCI and incomplete ST resolution

Incomplete ST resolution after primary percutaneous coronary interventions (pPCI) in STEMI patients is a well known prognostic marker, associated with the occurrence of microvascular obstruction and increased mortality. The effects of the use of glycoprotein IIbIIIa inhibitors (GPIs) in this peculiar subset of high- risk patients is still unknown. The aim of the present study was to assess whether the GPIs administration would result in improved outcome in ST elevation myocardial infarction (STEMI) patients with incomplete ST resolution (ISTR).All consecutive STEMI patients who underwent pPCI at our hospital between 2005 and 2014 were enrolled (n = 2001). ST resolution was defined as incomplete with a < 70% resolution of initial ST shift. Mortality analyses were performed by Kaplan-Meier curves, multivariable analysis through Cox regressions and propensity matching score. The incidence of ISTR was 29% (n = 592). Among ISTR patients, GPIs use was an independent predictor of better prognosis (HR 0.39, 95% CI 0.16–0.96, p < 0.04). Propensity matched analysis confirmed that the use of GPIs was associated with a lower 30-day (6.1% vs 13.4%, p = 0.02) and 1-year (8.4% vs 15.1%, p = 0.045) mortality. STEMI patients treated with pPCI and presenting ISTR show a poor outcome. The use of GPIs in these patients is associated with improved survival at 30 days and at 1 year; the causes for these favorable effects remain speculative and could be related to the development and evolution of microvascular obstruction.

Bivalirudin with a post-procedure infusion versus heparin monotherapy for the prevention of stent thrombosis.

To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy. Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI). Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST. Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI. For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Bivalirudin Versus Heparin During Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction.

BackgroundThe aim of the study was to compare the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in patients with acute myocardial infarction who undergo percutaneous coronary intervention (PCI). Earlier trials comparing bivalirudin and UFH during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. Since then, adjunct antiplatelet strategies have evolved. Improved upstream platelet inhibition with potent P2Y12 inhibitors decreased the need for routine glycoprotein IIb/IIIa inhibitor (GPI), resulting in similar outcomes among UFH and bivalirudin. Therefore, the role of bivalirudin in modern PCI practices is questionable.MethodsWe utilized Cochrane Review Manager (RevMan) 5.3 to perform a meta-analysis of seven randomized controlled trials (RCTs) with 22,844 patients to compare bivalirudin to UFH in patients with acute myocardial infarction requiring revascularization.ResultsThere was no difference between bivalirudin and UFH regarding major adverse cardiac events (MACE), risk ratio (RR) 0.99, 95% confidence interval (CI) 0.87 - 1.12; P = 0.83) or cardiovascular mortality (RR 0.87, 95% CI 0.71 - 1.07; P = 0.18). Bivalirudin increased acute stent thrombosis (RR 2.77, 95% CI 1.49 - 5.13; P = 0.001), which was only significant among ST-elevation myocardial infarction (STEMI) only trials. Bivalirudin caused less major bleeding (RR 0.66, 95% CI 0.49 - 0.90; P = 0.007), which was negated when GPI was used provisionally (RR 0.93, 95% CI 0.64 - 1.33; P = 0.67).ConclusionsAmong patients with acute myocardial infarction who underwent PCI, bivalirudin and UFH demonstrated similar MACE and cardiovascular mortality. Bivalirudin increased acute stent thrombosis, which was more remarkable among STEMI. Bivalirudin decreased major bleeding, but this benefit was negated when GPI was used provisionally.

Effect of early tirofiban administration on N-terminal pro-B-type natriuretic peptide level in patients treated with primary percutaneous coronary intervention.

To investigate the potential association between early tirofiban treatment and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after primary percutaneous coronary intervention (PCI). Whether the use of adjunctive early glycoprotein IIb/IIIa inhibitors (GPIs) therapy, may affect the level of NT-proBNP after primary PCI is poorly studied. Nine hundred and eighty four ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI were randomized to either pre-hospital tirofiban administration or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hr after PCI. There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post-PCI. Post-PCI NT-proBNP level dichotomized with median value as cut-off (968.8 pg/mL, IQR 430.9-1970.0) was significantly lower in patients treated with early tirofiban as compared to placebo (45.5% vs. 54.2% P = 0.011). At multivariate logistic regression analysis, independent predictors of post-PCI NT-proBNP level above the median were: NT-proBNP baseline level (OR 5.19; 95% CI, 2.92-9.25, P < 0.001), Killip class>I (OR 4.07; 95% CI 1.24-13.36, P = 0.021), anterior infarct location (OR 2.61; 95% CI 1.84-3.70, P < 0.001), age (years) (OR 1.04; 95% CI 1.03-1.06, P < 0.001), male gender (OR 0.38; 95% CI 0.26-0.57, P < 0.001), prior PCI (OR 0.49; 95% CI 0.27-0.90, P = 0.021) and tirofiban administration (OR 0.71; 95% CI 0.51-0.99; P = 0.045). In a large cohort of STEMI patients, pre-hospital tirofiban administration was independently associate with a lower risk of high NT-proBNP level after primary PCI, supporting the potential benefit of early antithrombotic treatment administration in STEMI patients. The trial is registered under No. ISRCTN06195297.

Characteristics and outcomes of patients requiring bailout use of glycoprotein IIb/IIIa inhibitors for thrombotic complications of percutaneous coronary intervention: An analysis from the CHAMPION PHOENIX trial

AimsTo describe the characteristics and outcomes of patients receiving bailout glycoprotein IIb/IIIa inhibitors (GPI) for thrombotic complications of percutaneous coronary intervention (PCI) in a large, contemporary trial. Methods and resultsIn the CHAMPION PHOENIX trial, the use of GPI was restricted to bailout for thrombotic complications. We describe the characteristics and outcomes of patients requiring bailout GPI compared to patients not receiving GPIs, with adjustment through propensity-score. A multivariable model was constructed to identify independent correlates associated with bailout GPI use.A total of 380 out of 10,942 patients received GPI (3.5%); GPI patients were younger, more frequently male, more likely to present with ST segment elevation myocardial infarction and less frequently treated with cangrelor. At 48 h, GPI patients experienced higher rates of the primary composite outcome of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis (ST) (19.2% vs 4.8%; adjusted OR: 5.65(4.08, 7.82), p < 0.0001) and a higher rate of GUSTO severe or moderate bleeding (2.6% vs 0.4% adjusted OR: 4.90 (1.98, 12.18), p = 0.0006) compared with non GPI patients. Independent correlates of GPI use were STEMI, use of unfractionated heparin, drug-eluting stents and longer procedure duration. ConclusionsIn a large contemporary trial, patients receiving bailout GPI for thrombotic complications of PCI experienced very high risks of both ischemic and bleeding complications, suggesting that prevention of periprocedural complications rather than bailout GPI may be preferable.Clinical Trial Registration: http://www.clinicaltrials.gov identifier: NCT01156571.

Comparison of In-Hospital Bleeding and Cardiovascular Events with High-Dose Bolus Tirofiban and Shortened Infusion to Short-Duration Eptifibatide as Adjunctive Therapy for Percutaneous Coronary Intervention

Potent platelet inhibition is one of the most important medical interventions to prevent ischemic complications during and after percutaneous coronary intervention (PCI). Practice has evolved with the introduction of potent oral P2Y12 inhibitors that provide quick, effective platelet inhibition, and the need for routine glycoprotein IIb/IIIa inhibitors (GPIs) has decreased. Additionally, a shorter duration of GPI infusion has been shown to be safe with adequate oral antiplatelet loading, but clinical outcome data are limited to eptifibatide. This single-center, retrospective cohort study analyzed in-hospital outcomes for patients who received adjunctive GPI therapy for PCI before and after an institution-wide switch to high-dose bolus tirofiban with shortened infusion from short-duration eptifibatide. The primary end point was a composite in-hospital outcome of major and minor bleeding and cardiovascular events (death, myocardial infarction, coronary artery bypass grafting, ischemic stroke, and target vessel revascularization). Secondary end points included bleeding and cardiovascular event types. A total of 357 and 446 patients received eptifibatide and tirofiban, respectively, from February 1, 2014 through September 30, 2017. Thirty five eptifibatide and 46 tirofiban patients experienced an in-hospital composite event (9.8% vs 10.3%, p = 0.81). There was no difference found between in-hospital bleeding (6.4% vs 5.4%, p = 0.52) or cardiovascular events (5.6% vs 6.5%, p = 0.60) with the use of eptifibatide or tirofiban, respectively. Multivariable analysis showed that patients with transradial access or an indication of unstable angina were less likely to experience an in-hospital composite event (OR 0.30 and 0.19, respectively, p <0.001 for both). In conclusion, the use of high-dose bolus tirofiban with shortened infusion versus short-duration eptifibatide was not associated with an increase of in-hospital bleeding or cardiovascular events.

Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: Insights from the TRANSLATE ACS study.

Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y12 inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y12 inhibitors are unclear. We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010-2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P < 0.001) than those without planned GPI use. Planned GPI was used less often with prasugrel/ticagrelor versus clopidogrel (37.1% vs. 43.3%), or when any P2Y12 inhibitor was given >6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99-1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13-1.59). Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE.

TCT-642 The Comparative Effectiveness and Safety of Cangrelor vs. In- lab Glycoprotein IIb/IIIa Inhibitor (GPI) in Patients Undergoing Percutaneous Coronary Intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)

Cangrelor is a recently approved intravenous P2 Y12 inhibitor for use in patients undergoing PCI. Glycoprotein IIb/IIIa inhibitors (GPI) are the more commonly used parenteral anti-platelet agent and are increasingly being used in an in-lab only fashion. The comparative efficacy of the two approaches

Planned use of GP IIb/IIIa inhibitors is safe and effective during implantation of the Absorb Bioresorbable Vascular Scaffold.

Bioresorbable Vascular Scaffolds (BVS) have the potential for adaptive vessel remodeling, restoration of vasomotion, and late luminal enlargement, thus allowing them to circumvent target lesion failures associated with bare metal stents (BMS) and drug-eluting stents (DES). However, recent data has shown a concerning increase in BVS-associated scaffold thrombosis (ScT) compared to DES. Upfront administration of GP IIb/IIIa inhibitors (GPIs) has shown to reduce early stent thrombosis (ST) compared to standard of care in BMS and DES. Since the use of GPIs was limited in BVS studies, the effect of GPIs on the rate of BVS-associated ScT is largely unknown. This is the first study investigating whether a planned use of GPIs during implantation of the Absorb BVS represents a safe and effective strategy in reducing ScT. In a retrospective chart review of 22 patients undergoing PCI with BVS implantation and planned GPI administration, no acute ScT, in-hospital MACE, or in-hospital major/minor bleeding events were observed. Bleeding reduction strategies such as shorter GPI infusion and radial access were implemented. This study provides valuable preliminary evidence on the benefit and safety in using planned GPI administration to reduce the incidence of ScT after implantation of BVS.

What is the Role for Glycoprotein IIb/IIIa Inhibitor Use in the Catheterization Laboratory in the Current Era?

In the era of dual antiplatelet therapy of aspirin and clopidogrel and systematic stent implantation, Glycoprotein IIb/IIIa Inhibitors (GPI), including abciximab, eptifibatide and tirofiban, proved beneficial in improving early outcome of Percutaneous Coronary Intervention (PCI), especially in higher risk clinical and/or anatomical subsets. This was associated however, with an increased incidence of bleeding complications. To review whether the established results of GPI in PCI are maintained in the contemporary era of more effective antiplatelet agents (i.e., prasugrel, ticagrelor and cangrelor) and safer anticoagulants (i.e., bivalirudin) and interventional techniques (i.e., radial approach). The most relevant evidence on the use of GPI in stable coronary artery disease, non-STelevation coronary syndromes and ST-elevation myocardial infarction was reviewed. Overall the relative efficacy and safety of GPI in contemporary PCI is maintained, largely irrespective of the use of more effective antiplatelet agents and/or safer anticoagulants and interventional techniques. However, an increase in the absolute occurrence of major and/or minor bleeding and/or need for blood transfusions is generally observed. Because of the persistent benefit of GPI in limiting early ischemic complications, especially in higher risk clinical and/or anatomical subsets, and the associated risk of increased bleeding complications, also in contemporary PCI, these agents should currently be used on a selective rather than routine basis, including bail out administration for peri-procedural thrombotic complications.

Bivalirudin versus heparin in percutaneous coronary intervention-a systematic review and meta-analysis of randomized trials stratified by adjunctive glycoprotein IIb/IIIa strategy.

Bivalirudin has been shown to be associated with less major bleeding than heparin in patients undergoing percutaneous coronary intervention (PCI); but the confounding effect of concomitant glycoprotein IIb/IIIa inhibitors (GPI) limits meaningful comparison. We performed a systematic review and meta-analysis to compare bivalirudin to heparin, with and without adjunctive GPI in PCI. We searched PubMed, Cochrane, EMBASE, CINAHL and WOS from January 2000 to December 2017 for clinical trials comparing bivalirudin to heparin, with and without adjunctive GPI during PCI. Cochrane's Q statistics were used to determine heterogeneity. Random effects model was used. Twenty-six comparison groups (22 original studies and 4 subgroup analyses) with 53,364 patients were included. Mean follow-up was 192±303 days. There was no difference between the two groups in all-cause mortality [risk ratio (RR: 0.93; 95% CI: 0.82-1.05, P=0.260), target vessel revascularization (TVR) (RR: 1.17; 95% CI: 0.93-1.46, P=0.174) or stroke (RR: 0.91; 95% CI: 0.71-1.18, P=0.490). Major bleeding was lower in the bivalirudin group with concomitant GPI in one or both arms (RR: 0.64; 95% CI: 0.53-0.77, P<0.001) and without (RR: 0.71; 95% CI: 0.51-0.99, P=0.041) provisional or routine GPIs. Bivalirudin appeared to have a higher risk of stent thrombosis (RR: 1.32; 95% CI: 1.04-1.68, P=0.022) and a trend towards more myocardial infarction (RR: 1.12; 95% CI: 0.98-1.28, P=0.098) though without statistical significance. However, exclusion of studies with GPI showed no difference in stent thrombosis or myocardial infarction with bivalirudin. Bivalirudin is associated with less major bleeding compared to heparin, regardless of GPI use. The lower anticoagulant effect of bivalirudin is linked with higher stent thrombosis and a trend towards more MI, however a confounding effect of GPI use in the heparin arm cannot be excluded.

The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary intervention for ST-elevation myocardial infarction: a systematic review and meta-analysis.

The aim of this meta-analysis was to compare the benefit of "early" vs. "delayed" P2Y12 inhibition in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). We conducted a meta-analysis including seven randomised controlled trials (RCTs) which compared early vs. delayed P2Y12inhibition in STEMI patients scheduled for PCI, providing data on major adverse cardiac events (MACE), all-cause death, and major bleeding. The primary endpoint was MACE. Secondary endpoints included stent thrombosis and the use of GP IIb/IIIa inhibitors (GPI). All endpoints were analysed at the shortest follow-up available. A total of 9,648 patients were included ("early"=4,792, "delayed"=4,856). "Early" P2Y12 inhibition was associated with a significant reduction in MACE rate (OR 0.73, 95% CI: 0.61-0.88, p=0.0008), myocardial infarction (OR 0.71, 95% CI: 0.57-0.90, p=0.004), bail-out GPI use (OR 0.87, 95% CI: 0.75-1.00, p=0.04) and improved coronary reperfusion before PCI (OR for Thrombolysis In Myocardial Infarction [TIMI] flow grade 2-3=1.12, 95% CI: 1.00-1.26, p=0.04). Major bleeding was not increased (OR 0.87, 95% CI: 0.62-1.21, p=0.41). A strategy of early effective P2Y12 inhibition in PCI of STEMI appears to improve coronary reperfusion before PCI, and reduce MACE, MI and bail-out GPI use without increase of major bleeding.

Incidence, Predictors, and Outcomes of Acquired Thrombocytopenia After Percutaneous Coronary Intervention: A Pooled, Patient-Level Analysis of the CHAMPION Trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition).

The influence of cangrelor on the incidence and outcomes of post-percutaneous coronary intervention (PCI) thrombocytopenia is not defined. We aimed to explore the incidence, predictors, and clinical impact of thrombocytopenia after PCI in cangrelor-treated patients. This was a pooled, patient-level analysis of the CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), which compared cangrelor with clopidogrel for prevention of thrombotic complications during and after PCI. Acquired thrombocytopenia was defined as either a drop in platelet count to <100 000 after PCI or a drop of >50% between baseline and a follow-up. The main efficacy outcome was major adverse cardiac events. The primary safety outcome was noncoronary artery bypass grafting-related Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries-defined severe bleeding at 48 hours. Patients (23 783) were enrolled, and 3009 (12.7%) received a GPI (glycoprotein IIb/IIIa inhibitor). Acquired thrombocytopenia occurred in 200 patients (0.8%). The adjusted rate of major adverse cardiovascular events at 48 hours was significantly higher in patients who developed thrombocytopenia compared with those who did not (odds ratio, 3.00; 95% confidence interval, 1.89-4.69; P<0.001), as was major bleeding (odds ratio, 14.71; 95% confidence interval, 5.96-36.30; P<0.001). GPI use was the strongest independent predictor of acquired thrombocytopenia (odds ratio, 2.93; 95% confidence interval, 2.15-3.97; P<0.0001). There was no difference in the rate of acquired thrombocytopenia in patients randomized to cangrelor or clopidogrel. Acquired thrombocytopenia after PCI is strongly associated with substantial early morbidity and mortality, as well as major bleeding. GPI use is a significant predictor of thrombocytopenia. Cangrelor is not associated with acquired thrombocytopenia, and its clinical efficacy and safety is consistent irrespective of thrombocytopenia occurrence. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00305162, NCT00385138, and NCT01156571.

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Bivalirudin versus heparin with primary percutaneous coronary intervention

BackgroundOptimal adjunctive therapy in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real-world population, using data from the Swedish national registry, SWEDEHEART. MethodFrom 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH ± GPI or bivalirudin±GPI. Primary outcomes included 30-day all-cause mortality and major in-hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. ResultsTreatment with UFH ± GPI was associated with similar risk of 30-day mortality compared to bivalirudin±GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82–1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between UFH ± GPI and bivalirudin±GPI. In contrast, treatment with UFH ± GPI was associated with a significant higher risk of major in-hospital bleeding (adjusted OR 1.62; 95% CI 1.30–2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92–1.70). ConclusionBivalirudin±GPI was associated with significantly lower risk for major inhospital bleeding but no significant difference in 30-day or one year mortality, stent thrombosis or re-infarction compared with UFH ± GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH.

Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes

BackgroundContrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). ObjectivesThis study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). ResultsAmong 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site−related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. ConclusionsIn patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)