Glycoprotein IIb/IIIa Inhibitors Research Articles

Bivalirudin in stable angina and acute coronary syndromes.

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes.

Yet Another Randomized Study of Bivalirudin in MI Patients

Several recent studies comparing bivalirudin with various heparin and/or glycoprotein IIb/IIIa inhibitor (GPI) strategies have yielded conflicting

Bivalirudin Versus Heparin Plus Glycoprotein IIb/IIIa Inhibitors in Patients with Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

Diabetes mellitus (DM) is a pro-thrombotic state with enhanced thrombin generation and platelet reactivity. For most patients undergoing percutaneous coronary intervention (PCI), bivalirudin demonstrates efficacy comparable with that of heparin and glycoprotein IIb/IIIa inhibitors (GPIs). Yet, because of their pro-thrombotic condition, we hypothesized that patients with DM may benefit from more aggressive dual antithrombin and antiplatelet therapy. The aim of this paper was to provide a systematic review comparing outcomes of PCI with bivalirudin versus heparin plus GPI in patients with DM using meta-analytical techniques. Eligible studies needed to have reported a subgroup analysis of outcomes among diabetic patients. Six trials comprising 5924 diabetic patients were eligible. At 30 days, bivalirudin was associated with a reduction in net adverse cardiac events [relative risk (RR) 0.81, 95% confidence interval (CI) 0.70-0.93, p=0.002] and major bleeds (RR 0.68, 95% CI 0.49-0.95; p=0.02), with no difference in composite ischemia (RR 0.92, 95% CI 0.74-1.14; p=0.43) or mortality (RR 0.71, 95% CI 0.45-1.13; p=0.15). At 1 year, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.73, 95% CI 0.54-1.00, p=0.05) despite similar composite ischemia (RR 1.02, 95% CI 0.56-1.21, p=0.811). In conclusion, thrombin inhibition with bivalirudin alone was associated with reduced 30-day major bleeding and 1-year all-cause mortality compared with heparin plus GPI in diabetic patients undergoing PCI.

Risk of thrombocytopenia with glycoprotein IIb/IIIa inhibitors across drugs and patient populations: a meta-analysis of 29 large placebo-controlled randomized trials.

Glycoprotein IIb/IIIa inhibitors (GPIs) reduce myocardial infarction and peri-procedural thrombotic complications in patients undergoing percutaneous coronary intervention (PCI); however, they may cause bleeding and thrombocytopenia, which are associated with poor clinical outcomes. Although the risk of bleeding has been well characterized, the extent of the risk of thrombocytopenia remains uncertain. In this meta-analysis, we aim to evaluate the risk of thrombocytopenia associated with GPI compared with placebo across drugs and patient populations. Risk ratios were calculated for thrombocytopenia (<100 000 platelets/mm(3)) and severe thrombocytopenia (<50 000 platelets/mm(3)) in 29 randomized large trials (>1000 patients) of GPI vs. placebo involving a total of 123 419 patients. We used meta-analysis techniques to estimate the summary effect across all trials, in pre-specified sub-groups, and in sensitivity analyses to assess the robustness of the data. Glycoprotein IIb/IIIa inhibitor use increases the rate of thrombocytopenia [risk ratio (RR) = 1.62, 95% confidence interval (CI) 1.48-1.78] and severe thrombocytopenia (RR = 3.52, 95% CI 2.87-4.30) compared with placebo. These findings are consistent by route of administration (oral vs. intravenous). Patients with ST-segment elevation myocardial infarction (RR 2.66, 95% CI 2.12-3.34) and elective PCI (RR 2.78, 95% CI 1.76-4.40) treated with a GPI had higher risks of thrombocytopenia than patients with non-ST-segment elevation acute coronary syndrome (RR 1.41, 95% CI 1.25-1.58; P < 0.001 for heterogeneity by sub-group). The administration of GPI compared with placebo was associated with a 63% increased risk of thrombocytopenia (<100 000 platelets/mm(3)), and >3-fold increased risk of severe thrombocytopenia (<50 000 platelets/mm(3)). This corresponds to an average of 10-20 additional cases of thrombocytopenia per 1000 patients given GPIs, of which 6-7 cases are severe.

Homocysteine and risk of periprocedural myocardial infarction in patients undergoing coronary stenting

Despite improvements in pharmacological and mechanical devices, the risk of periprocedural myocardial infarction (PMI) is still high, particularly in prothrombotic conditions. Hyperhomocysteinemia has been associated with enhanced platelet function, impaired endothelial function and prothrombotic status, thus increasing the risk of cardiovascular events. No study has, so far, investigated the relationship between homocysteine levels and the risk of periprocedural MI in patients undergoing percutaneous coronary intervention (PCI), and this is therefore the aim of the current study. In 1150 patients undergoing PCI, homocysteinemia was assessed at admission. Cardiac biomarkers were measured at intervals from 8 to 48 h after PCI. Periprocedural myonecrosis was defined by a troponin I increase to three times the upper limit of normal (ULN) or by 50% if elevated at the time of the procedure. PMI was defined as a CK-MB increase to three times the ULN or of 50% if elevated at the time of the procedure. We grouped patients according to tertile values of homocysteine. Higher homocysteine levels were associated with older age (P < 0.001), male sex (P = 0.02), arterial hypertension (P = 0.007), diabetes (P = 0.04), renal failure (P < 0.001), higher creatinine levels (P = 0.01), previous MI (P = 0.02), previous PCI (P = 0.04) and previous cerebrovascular accidents (P = 0.01). Homocysteine was associated with lower ejection fraction (P < 0.001), treatment with angiotensin-receptor blockers (P < 0.001), nitrates (P = 0.008) and diuretics (P < 0.001) and acetylsalicylic acid (P = 0.01). Homocysteine levels were directly related with the extent of coronary disease (P = 0.04) and coronary calcifications (P < 0.001) but inversely with type C lesions (P = 0.001), TIMI 3 flow pre-PCI (P = 0.02), stenosis severity (P = 0.01) and thrombus (P = 0.004). In addition, they are associated with higher rates of balloon predilatation (P = 0.02), lower use of thrombectomy (P = 0.01) and periprocedural administration of GPIIbIIIa inhibitors (P = 0.02). Ageing, male sex, diabetes, renal failure, creatinine levels, diuretics use, coronary calcifications and type C lesions were independently related to homocysteine. Homocysteine did not affect the risk of PMI [adjusted odds ratio (OR) 1.14 (0.91-1.42), P = 0.26], or periprocedural myonecrosis [adjusted OR 1.17 (0.98-1.39), P = 0.08]. Similar results were found after propensity score adjustment [adjusted OR 1.19 (0.95-1.48), P = 0.14 for PMI and adjusted OR 1.18 (0.99-1.4), P = 0.07 for myonecrosis] and at subgroup analysis in higher risk subsets of patients. In patients undergoing PCI, the risk of PMI is not influenced by hyperhomocysteinemia.

Heparin is Not Inferior to Bivalirudin in Percutaneous Coronary Intervention-Focusing on the Effect of Glycoprotein IIb/IIIa Inhibitor Use: A Meta-Analysis.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

Impact of Time from Symptom Onset to Drug Administration on Outcome in Patients Undergoing Glycoprotein IIb-IIIa Facilitated Primary Angioplasty (from the EGYPT Cooperation)

Contrasting data have been so far reported on facilitation with glycoprotein IIb-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the aim of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein IIb-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (≤65 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIMI 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival.

Bivalirudin Versus Heparin With or Without Glycoprotein IIb/IIIa Inhibitors in Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention

In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin+ a glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI. The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI. Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials. A total of 5,800 patients were randomized to bivalirudin (n= 2,889) or heparin ± GPI (n= 2,911). The radial approach was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p< 0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p= 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p= 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; p< 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p< 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups. Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions comparedwith heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).

Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography).

This study sought to determine clinical, procedural, and treatment factors associated with acute stent thrombosis (AST) in the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial. Bivalirudin started during transport for primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction significantly reduced major bleeding compared with heparin with or without glycoprotein IIb/IIIa inhibitors (GPI), but it was associated with an increase in AST. We compared patients with (n = 12) or without AST (n = 2,184) regarding baseline, clinical, and procedural characteristics and antithrombotic treatment strategies (choice of P2Y12 inhibitor, post-primary PCI bivalirudin infusion dose [0.25 mg/kg/h, or BIV-LOW] vs. [1.75 mg/kg/h, or BIV-PCI] vs. heparin ± GPI). Logistic regression was performed to identify independent correlates of AST. The overall AST rate was 0.6% and was higher with bivalirudin than with heparin ± GPI (1.1% vs. 0.2%; p = 0.007). Median time to AST was 2.3 h (interquartile range: 1.9 to 2.8 h). Patients with AST had less hypertension (2 of 14 [14.0%] vs. 961 of 2,182 [44.0%]; p = 0.03), and more frequently received GPI (11 of 14 [78.6%] vs. 880 of 2,183 [40.3%]; p = 0.004). Multivariate analysis using Firth penalized maximum likelihood estimation found hypertension (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.07 to 0.92; p = 0.037) and BIV-LOW (OR: 5.8, 95% CI: 1.5 to 22.2; p = 0.010) predictive of AST. Choice of P2Y12 inhibitor had no impact on AST. Compared with heparin ± GPI, AST rates were higher for BIV-LOW (11 of 670 [1.6%] vs. 2 of 947 [0.2%]; p = 0.008), but not different for BIV-PCI (1 of 244 [0.4%]; p = 0.588). In this post-hoc analysis from EUROMAX, AST occurred very early and was not mitigated by the novel P2Y12 inhibitors. Prolonging the bivalirudin infusion at the PCI dose (but not at a lower dose) appeared to mitigate the risk of AST.

Antiplatelet and anticoagulant nonuse for acute myocardial infarction in the emergency department: An analysis from the National Hospital Ambulatory Medical Care Survey, 2002-2010

Background: Recent reports from quality improvement registries revealed high antiplatelet and anticoagulant use within 24 h of hospitalization for acute myocardial infarction (AMI). Objective: To produce an unbiased national estimate of the use of antiplatelets and anticoagulants during visits to the emergency department (ED) for AMI. Methods: Data from the National Hospital Ambulatory Medical Care Survey for AMI visits from 2002 to 2010 were analyzed. The complex survey design was taken into consideration to ensure that reliable national estimates were produced. Results: During the study period, there were 3,825,905±308,534 estimated eligible ED visits for AMI. Acetylsalicylic acid was not used in 55.5±2.9%, 55.7±4.0% and 55.2±4.8% of visits in 2002 to 2004, 2005 to 2007 and 2008 to 2010, respectively (Ptrend=0.96). The nonuse of thienopyridine or glycoprotein IIb/IIIa inhibitors (GPI) decreased during this period (92.9±1.4%, 88.1±2.6% and 83.4±3.4%, respectively; Ptrend=0.001). Anticoagulant nonuse did not change (72.1±2.6%, 68.0±3.7% and 65.5±4.4%, respectively; Ptrend=0.14). Even in definitive AMI visits, nonuse was high (acetylsalicylic acid, 48.7±4.5%, 44.7±6.2% and 55.6±5.6%, respectively, Ptrend=0.31; thienopyridine/GPI, 81.9%±3.4%, 77.0±5.0% and 71.1±5.5%, respectively, Ptrend=0.001; and anticoagulants, 49.3±9.6%, 47.1±7.1% and 45.3±6.20%, respectively, Ptrend=0.24). ED visits in a metropolitan statistical area were more likely to receive acetylsalicylic acid (OR 2.27 [95% CI 1.02 to 5.09]) and anticoagulants (OR 3.34 [95% CI 1.54 to 7.24]). Similarly, visits evaluated by a consulting physician were more likely to receive thienopyridine/GPI (OR 2.24 [95% CI 1.22 to 4.13]) and anticoagulants (OR 1.73 [95% CI 1.14 to 2.63]). Conclusion: In a significant proportion of AMI visits, including definitive AMI, antiplatelet and anticoagulant therapies were not administered in the ED.

2014 AHA Late-Breaking Basic Science Abstracts

### 24178 ### MAVS Mediates Protection against Myocardial Ischemic Injury with Hydrogen Sulfide David Durrant, Adolfo G Mauro, Juan Valle Raleigh, Anindita Das, Jun He, Khoa Nguyen, Stefano Toldo, Antonio Abbate, Fadi N Salloum; Virginia Commonwealth Univ, Richmond, VA Background : Hydrogen sulfide (H2S) has been shown to protect against myocardial ischemic and inflammatory injury in part by preserving mitochondrial integrity. Since mitochondrial antiviral signaling (MAVS) protein has been implicated in attenuating Bax-mediated cytochrome c release from mitochondria caused by oxidative stress or ischemia, we sought to determine whether MAVS mediates the cardioprotective effects of H2S. Methods and Results : After baseline echocardiography, adult male wild type (WT) or MAVS KO mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min. followed by 24 h reperfusion. Mice were pretreated with Na2S (100 μg/kg; ip ) or saline 1 h before MI. Infarct size, measured with TTC staining, was reduced and LV fractional shortening (FS) was preserved with Na2S at 24h post MI in WT mice as compared to saline-treated mice, but not in MAVS KO mice (Figs. A and B). The risk area was not different between the groups. Western blot analysis revealed a significant decline in myocardial MAVS expression at 24h post MI, which was preserved with Na2S (Fig. C). Another subset of mice was subjected to permanent coronary artery occlusion and treated with Na2S or saline daily for 28 days. LVFS decreased significantly at 28 days post-MI in the saline group, but was significantly preserved with Na2S (Fig. D). Moreover, LV infarct scar size, assessed by trichrome staining, was smaller in Na2S group (22.4 ± 2.7%) as compared to control (33.5 ± 2.1%, P<0.05). Survival rate was 2 fold higher with Na2S compared to saline (P<0.05). Western blot analysis confirmed a significant …

Abstract 16476: Safety Profile of Bivalirudin in the Treatment of ST-Segment Elevation Myocardial Infarction Patients in Clinical Practice - Results From the Bremen STEMI Registry

Introduction: Previous studies demonstrated that treatment of patients (pts) being affected by ST-segment elevation myocardial infarction (STEMI) with bivalirudin (biv) instead of heparin (hep) reduced rates of major bleedings. Results regarding a reduction in all-cause mortality are inconclusive, stent thromboses however were slightly increased. Real world data in pts with STEMI treated with biv in the era of new anti-thrombotic treatment are still spare. The aim of this study was to evaluate safety of biv for all-comers. Methods: All pts with STEMI from the metropolitan area of Bremen (Germany) are admitted to the Bremen heart center and documented in the Bremen STEMI-registry (BSR) since 2006. In May 2013 we adapted our anticoagulation strategy to the current guidelines from hep with glycoprotein IIb/IIIa inhibitors (GPI) to biv with provisional use of GPI. Pts receiving biv were compared to all pts until April 2013 in the BSR without chronic renal failure. Results: Baseline and interventional characteristics of 530 consecutive pts treated with biv and 5197 pts treated with hep are shown in table 1. Despite a higher portion of pts after resuscitation (10.3% vs 8.6%; p&lt;0.01) and a higher incidence of Killip class 3 or 4 (15% vs 8%; p&lt;0.001) in the biv group inhospital all-cause mortality showed no difference (biv: 6.8% vs hep: 7.3%, p=0.66). However pts treated with biv demonstrated highly significant lower bleeding rates (TIMI major/minor bleedings: 0.8% vs 3.7%, p&lt;.01). Stent-thromboses showed a trend towards an increased event rate with biv (1.3%, 7pts vs 1.0%, 52pts, p=0.07). Conclusions: In one of the largest all-comers registries treatment with biv was associated with significantly lower minor and major bleedings. There is only a trend for a higher rate of stent thromboses in the biv group. Therefore, data from our all-comers registry support the beneficial safety profile of biv observed in clinical studies.

Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndrome.

The aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS). Bivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear. A total of 13 randomized, controlled trials involving 24,605 patients were included. There was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤ 24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly. Overall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI.

Chronic vitamin K antagonist therapy and bleeding risk in ST elevation myocardial infarction patients

ObjectivesAcute management of ST elevation myocardial infarction (STEMI) patients on chronic vitamin K antagonist (VKA) therapy is uncertain. This study aims to estimate in-hospital major bleeding risk among STEMI patients...

Infarctus du sujet jeune : à physiopathologie particulière, prise en charge singulière ?

We report the case of a 24-year-old patient admitted for anterior ST segment elevation myocardial complicated by ventricular fibrillation and revealing thrombotic sub occlusion of the left anterior descending coronary artery. Revascularization is achieved by manual thrombectomy and use of Glycoprotein GPIIbIIIa inhibitors and permits to restore TIMI 3 flow. Given the large thrombotic burden, the patient is initially treated medically (optimal anti thrombotic therapy without stenting) and benefits from angiographic control 48hours later with imaging by Optical Coherence Tomography (OCT). It shows a reduction of thrombus burden and lack of significant underlying organic lesion (no organic stenosis or plaque rupture). In view of these data, it was decided to continue medical treatment alone without stenting. OCT imaging at 6 months shows atheroma without stenosis, thrombus or plaque rupture. This young patient remains asymptomatic and recovered normal left ventricular function with a 2-year follow-up.

TCT-825 Bleeding events are reduced and survival improved by use of radial access during primary percutaneous coronary intervention for patients receiving glycoprotein inhibitors

access during primary percutaneous coronary intervention for patients receiving glycoprotein inhibitors Control Number: 2917 Submission Type: Abstract Presentation Format: Poster Only New Device/Innovation: No Author(s): Adam J Brown, Nikil K Rajani, Liam M McCormick, Stephen P Hoole, Nick E West Institution(s): University of Cambridge, Cambridge, United Kingdom, Papworth Hospital, Cambridge, United Kingdom Presenter Poster: Dr Adam J Brown, MB BChir View Disclosure University of Cambridge Background: Use of glycoprotein IIb/IIIa inhibitors (GPI) during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is known to improve myocardial perfusion and reduce further ischemic events, but is associated with an increase in bleeding risk. Performing PPCI via radial access (rPPCI) is thought to reduce post-procedural bleeding complications and may improve overall survival. We sought to assess whether rPPCI is associated with improved outcomes in patients receiving GPI at our institution. Methods: Consecutive patients undergoing PPCI for STEMI over a four-year period were included. All patients were preloaded with 600mg clopidogrel and 300mg aspirin en-route to PPCI. Interventional strategy and GPI use were left to operator discretion. Patient data and outcome measures were obtained by interrogation of notes and national databases. Bleeding complications were categorized using Bleeding Academic Research Consortium (BARC) definitions. Results: 2,019 patients were included in the analysis (mean age 64.2±12.4yrs, 75.9% male), with 863 receiving GPI. Patients that received GPI were younger (62.7±11.8yrs vs. 64.8±12.6yrs, p< 0.001), more likely to be male (80.5% vs. 73.9%, p< 0.001) but had a higher incidence of cardiogenic shock (5.6% vs. 2.7%, p=0.002). Other baseline demographics were similar. Overall, BARC defined bleeding was more prevalent in those receiving GPI (BARC ≥2 3.0% vs. 0.7%, p< 0.001; BARC ≥3 2.6% vs. 0.2%, p< 0.001). However, patients undergoing rPPCI with GPI had lower bleeding rates when compared with femoral access (0.8% vs. 3.7%, p=0.05). For patients receiving GPI, rPPCI resulted in a significant improvement in 1-year survival (99.2% vs. 93.5%, p=0.01; OR 0.12, 95%CI 0.02-0.87, p=0.04). However, in patients not receiving GPI, no survival benefit for rPPCI was observed (94.4% vs. 93.7%, p=0.70; OR 0.87, 95%CI 0.44-1.71, p=0.69). Conclusions: rPPCI results in lower rates of bleeding and improved survival in patients receiving GPI during PPCI. rPPCI should be considered in patient groups where subsequent use of GPI is likely. CORONARY: STEMI and NSTEMI

Heparin monotherapy for percutaneous coronary intervention?

The efficacy and safety of percutaneous coronary intervention (PCI) has been substantially enhanced by refinements in antithrombotic treatments. Ischaemic complications were reduced by as much as 50% with addition of platelet glycoprotein IIb/IIIa inhibitors (GPIs) to early regimens of aspirin and heparin. 1,2 However, use of these potent platelet inhibitors was accompanied by increased risk of haemorrhagic complications, which are associated with increased mortality, morbidity, and costs. 3,4 Development of antithrombotic drugs therefore focused on reducing risks of haemorrhagic events while maintaining protection against ischaemic complications.

Bridging: Perioperative management of chronic anticoagulation or antiplatelet therapy

Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective in preventing thromboembolic diseases. In case of interventional of surgical procedures patients with indications for chronic anticoagulation [atrial fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet agents [cerebrovascular events, cardiovascular events] will require interruption of antithrombotic/antiplatelet therapy with the need of replacement with a short-acting agent. Due to limited data available from randomized studies and meta-analyses the evidence level is low in the majority of recommendations. Therefore for each patient the bleeding and thrombosis risk depending on the individual patient constitution and the planned intervention must be weighted. In patients with an intermediate risk for thrombosis the bleeding risk of the scheduled intervention will influence the bridging recommendation: In patients with a low bleeding risk oral anticoagulation/antiplatelet therapy can be continued or reduced in intensity. In patients with an intermediate or high bleeding risk along with a low thrombosis risk a temporary interruption of the anticoagulation/antiplatelet therapy is feasible. In patients with a high thrombosis and bleeding risk anticoagulation should be bridged with unfractionated heparin [renal insufficiency] or low molecular weight heparin. In the latter risk situation, inhibition of platelet function can be achieved with short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to intervention patients treated with the new oral anticoagulants [Dabigatran; Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation depending on the individual drug half-life and their renal function. Bridging therapy with heparin prior to intervention is not necessary with the new oral anticoagulants.

Efficacy of Pre-Hospital Use of Glycoprotein IIb/IIIa Inhibitors in ST-Segment Elevation Myocardial Infarction Before Mechanical Reperfusion in a Rapid-Transfer Network (from the Acute Myocardial Infarction Registry of Brittany)

Previous studies investigating prehospital use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction reached conflicting conclusions. The benefit of this strategy in addition to in-ambulance loading of dual-antiplatelet therapy remains controversial. The aim of this study was to analyze data from a prospective registry of patients with ST-segment elevation myocardial infarctions admitted <24 hours after symptom onset (July 2006 to May 2012). A total of 2,052 patients managed in a physician-staffed mobile intensive care unit (MICU)<12 hours after symptom onset and scheduled for primary percutaneous coronary intervention (PPCI) were retrospectively included. Patients who received GPIs in the MICU were compared with those who did not. The primary end point was infarct-related artery patency, defined as pre-PPCI Thrombolysis In Myocardial Infarction (TIMI) flow grade 3. GPIs were administered in the MICU to 737 patients (36%), including 430<2 hours after symptom onset, and 1,315 patients (64%) did not received prehospital GPIs. Pre-PPCI TIMI flow grade 3 rate was lower in patients treated in the MICU (17.2% vs 21.3%, p=0.03) because of patients treated >2 hours after symptom onset, of whom only 12.7% reached the primary end point. There was no significant difference between groups in the rate of in-hospital major adverse cardiac events. In conclusion, prehospital GPI use in patients with ST-segment elevation myocardial infarctions<12 hours after symptom onset scheduled for PPCI neither improved pre-PPCI infarct-related artery patency nor reduced in-hospital major adverse cardiac events.

Impact of antithrombotic treatment on short-term outcomes after percutaneous coronary intervention for left main disease: a pooled analysis from REPLACE-2, ACUITY, and HORIZONS-AMI trials

Percutaneous coronary intervention (PCI)-related risks are increased among patients with left main disease (LMD). The aim was to evaluate the impact of antithrombotic therapy on outcomes after LMD PCI in a predominantly ACS population. One hundred and seventy-seven patients undergoing LMD PCI were identified in a pooled dataset of 14,326 patients from three large randomised trials comparing treatment with heparin plus glycoprotein IIb/IIIa inhibitors (GPI) or bivalirudin alone, including the REPLACE-2, ACUITY and HORIZONS-AMI trials. Overall, net adverse clinical events (NACE) and non-CABG major bleedings at 30 days occurred more frequently in patients undergoing LMD PCI compared to the overall non-LMD PCI population (NACE: 19.8% vs. 10.6%, p≤0.001, major bleeding: 9.6% vs. 4.6%, p≤0.001). In the LMD group, bivalirudin was associated with significantly less non-CABG related major bleeding compared to heparin+GPI (4.5% versus 14.6%, relative risk [RR] 0.27, 95% CI: 0.09-0.83; p=0.013), while the composite ischaemic endpoint (death/MI/TVR) at 30 days was similar in the two groups (11.4% vs. 12.4%, p=0.513) resulting in a benefit on NACE for bivalirudin over heparin+GPI (14.8% vs. 24.7%; RR 0.53; p=0.039). Among patients undergoing LMD PCI, the use of bivalirudin instead of heparin+GPI resulted in significantly less major bleeding and improved short-term net clinical outcome. Bivalirudin may be the preferred anticoagulation strategy in LMD PCI patients.