Glycoprotein IIb/IIIa Inhibitors Research Articles

Abstract 78: The Association of Home Warfarin Therapy with Acute Treatment Patterns and Bleeding Risk in Patients Presenting with ST-Elevation Myocardial Infarction: Results from the NCDR ®

Introduction: Bleeding complications during acute coronary syndrome care are independent predictors of adverse outcomes. Patients presenting with ST-elevation myocardial infarction (STEMI) receiving warfarin therapy at home represent a management challenge especially in the absence of specific recommendations in current guidelines. Given the paucity of data, this study aims to describe the acute treatment patterns and bleeding risk in STEMI patients treated with primary percutaneous coronary intervention (PCI). Methods: We examined 120,270 STEMI patients treated with primary PCI at 586 ACTION Registry ® -GWTG TM hospitals between 2007- 2012, excluding patients who died within the first 24 hours. A total of 3,101 patients (2.6%) were on home warfarin. Antiplatelet and anticoagulant regimens within the first 24 hours of admission were compared between patients taking and those not taking warfarin at home. The association between home warfarin therapy and risk of in-hospital major bleeding was analyzed using multivariable logistic generalized estimating equations method. Results: STEMI patients on home warfarin were older and had higher prevalence of co-morbid conditions such as hypertension, diabetes, and renal disease compared with those not taking warfarin; at presentation only 35.6% of patients had INR ≥2.0. They were less likely to receive prasugrel and heparin, but more likely to receive clopidogrel and bivalirudin compared with those not on home warfarin (Table). Glycoprotein IIbIIIa inhibitors were also less commonly administered to patients taking warfarin at home (Table). Door-to-balloon ≤90 minutes for direct arrivals and ≤120 minutes for transfers were less likely to be achieved in patients on home warfarin (83.5% vs. 88.5%, p<0.0001 and 47.5% vs. 57.1%, p<0.0001, respectively). Home warfarin therapy was associated with significantly higher risk of in-hospital major bleeding (17.0% vs 10.1%; adjusted odds ratio 1.26 [1.13-1.40]). Conclusions: In STEMI patients treated with primary PCI, home warfarin therapy is associated with significant increase in the risk of in-hospital major bleeding despite the less frequent use of treatment regimens associated with higher bleeding risk. Future studies are needed to identify bleeding avoidance strategies in this high-risk population.

Glycoprotein IIb-IIIa inhibitors – Do we still need them?

Platelets play central role in thrombotic events in acute coronary syndromes (ACS) and during percutaneous coronary interventions (PCI). Platelet activation occurs through various mechanisms and all culminate in expression of the surface GP IIb-IIIa receptors which mediate their aggregation and thrombosis. Glycoprotein IIb-IIIa inhibitors (GPI) remain the most powerful antiplatelet agents by inhibiting this final common pathway of platelet activation. The role of GPI in the treatment of coronary ischemic events has evolved through the past 20 years. Given their potent antiplatelet activity and consistent anti-ischemic benefit in major trials, they were an integral part of antiplatelet – antithrombin portfolio in the treatment of ACS and during PCI over a decade. However, the advent of stents and thienopyridine ticlopidine and later clopidogrel made periprocedural ischemic complications less common and GPI had slowly lost its importance in routine low-risk PCI. Though GPI reduced periprocedural ischemic complications, increased bleeding events continued to be a major problem. In the recent years, bleeding has increasingly been recognized as a major determinant of clinical outcomes both with ACS and PCI. Recently, the availability of bivalirudin as an equally effective and safer periprocedural anticoagulant, heparin and GPI have slowly been pushed to second place over the entire spectrum of coronary interventions. The newer antiplatelets which provide rapid and more consistent antiplatelet action further reduced the role of GPI to a very small subset of patients where ischemic risk far exceeds the thrombotic risk.1–3 This editorial briefly evaluates the current role of GPI in the background of recent major studies with newer antiplatelets and bivalirudin.

Bleeding outcomes after routine transradial primary angioplasty for acute myocardial infarction using eptifibatide and unfractionated heparin: A single‐center experience following the HORIZONS‐AMI trial

We sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS-AMI. HORIZONS-AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI). This was a single-center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty-day major bleeding was defined as per the HORIZONS-AMI criteria and also according to TIMI and GUSTO scales. Of the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS-AMI. In contrast with HORIZONS-AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0-6.3%] vs. 4.9% [4.0-6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8-4.1%] vs. 3.1% [2.3-3.4%], P = 0.10) and GUSTO severe or life-threatening bleeding (0.6% [0.1-2.5%] vs. 0.4% [0.2-0.9%], P = 0.75) were comparable. Routine TR access for PPCI using UFH plus GPI is associated with a low 30-day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS-AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates.

ASSA13-15-18 Efficacy and Safety of Bivalirudin Versus Heparin Plus Glycoprotein IIB/IIIA Inhibitors in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomised Trials

<h3>Background and Objective</h3> Recently, several randomised trials which compared bivalirudin with heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing percutaneous coronary intervention (PCI) had been published. The purpose of this study was to perform an up-to-date meta-analysis of randomised trials on the effectiveness and safety of bivalirudin versus heparin plus GPIs in patients undergoing PCI. <h3>Methods</h3> All published clinical randomised trials which compared heparin plus GPIs with bivalirudin in patients undergoing PCI were included. The literature was searched by electronic databases which contained MEDLINE, Pubmed, Elsevier, Cochrane clinical trials and Clinical Trials.gov database from January 2000 to December 2011. <h3>Results</h3> Ten randomised trials enrolling 21,932 patients were included. Compared with heparin plus GPIs, bivalirudin associated with lower rates of major bleeding (P &lt; 0.00001), minor bleeding (P &lt; 0.00001), long-term mortality (P = 0.02), and short-term net clinical adverse events (P = 0.004). There was no significantly different rates of the major adverse cardiovascular events (≤30 days: P = 0.26; &gt; 30 days: P = 0.10) and myocardial infarction events (≤30 days: P = 0.19; &gt; 30 days: P = 0.84) between two groups. However, bivalirudn administration resulted in an increased long-term incidence of target vessel revascularization (P = 0.02) and a high trend in individual definition of revascularization (P = 0.07). <h3>Conclusions</h3> Among the patients who undergoing PCI, anticoagulation with bivalirudin results in significantly lower rates of bleeding, long-term mortality and short-term net clinical adverse events when compared with heparin plus GPIs. Even that bivalirudin had high long-term risk of target vessel revascularization, there are no different in MACE and MI events between two groups.

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Glycoprotein IIb/IIIa inhibitors with or without thienopyridine pretreatment improve outcomes after primary percutaneous coronary intervention in high‐risk patients with ST elevation myocardial infarction—a meta‐regression of randomized controlled trials

Recent studies have casted a doubt on usefulness of routine glycoprotein IIb/IIIA inhibitors (GPI) in patients, pretreated with aspirin and clopidogrel, undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). We aimed to investigate the effect of relevant factors, particularly thienopyridine pretreatment, on clinical benefit from GPI in randomized controlled trials (RCT). We searched electronic databases for RCT comparing GPI to control in patients with STEMI undergoing primary PCI. Relevant study covariates and clinical outcomes were extracted. A random effect cumulative and subgroup analyses (thienopyridine non-pretreated studies vs. pretreated studies) were performed. A weighted random effect meta-regression to determine the effect of thienopyridine pretreatment, enrollment year, control group mortality, and ischemic time on mortality benefit from GPI use was conducted. Twenty studies (9 non-pretreated, 11 pretreated) with a total of 7,414 patients (3,811 GPI, 3,603 control) were included. GPI use reduces mortality (risk ratio, RR = 0.75 95% confidence interval (CI) 0.57-0.97, P = 0.03), target vessel revascularization (TVR) (RR = 0.63, 95% CI 0.50-0.80, P = 0.0002), but not reinfarction (RR = 0.66, 95% CI 0.44-1.0, P = 0.05) at 30 days. There was no effect of thienopyridine pretreatment on reduction in mortality (P = 0.39), reinfarction (P = 0.46), or TVR (P = 0.95) in subgroup analysis. Meta-regression analyses showed significant effect of control group mortality risk (B = -12.15, P = 0.034) but not of thienopyridine pretreatment, enrollment year or control group ischemic time on mortality reduction from GPI use. The benefit from GPI use in primary PCI for STEMI appears to depend on mortality risk, and not on thienopyridine pretreatment.

Bivalirudin for the Treatment of ST-Segment Elevation Myocardial Infarction: A NICE Single Technology Appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer (The Medicines Company) of bivalirudin to submit evidence for its clinical and cost effectiveness within its licensed indication for the treatment of adults with ST-segment elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention (PPCI), as part of NICE's single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG), which produced a review of the evidence within the manufacturer's submission to NICE. This article describes the manufacturer's submission, the ERG review and NICE's subsequent decisions. The main evidence was derived from one randomized controlled trial (RCT) of STEMI patients intended for PPCI, comparing bivalirudin with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors (GPIs). Bivalirudin was associated with a significant reduction in cardiac mortality at 30days (p=0.03) and at 1-year follow-up (p=0.005), and a significant reduction in major bleeding at 30days (p<0.001) and 1year (p<0.0001), compared with heparin plus GPI. Stent thrombosis up to 24 hours following PPCI was significantly (p<0.001) more common with bivalirudin. However, there was no significant treatment effect for stent thrombosis from 1 to 30days (p=0.28), or at 1-year follow-up (p=0.53). There were no significant treatment group differences at 30days and at 1year in stroke (p=0.68 and p=0.99, respectively), in myocardial infarction [MI] (p=0.90 and p=0.22, respectively), or in the need for the revascularization of the target vessel for ischaemia (p=0.18 and p=0.12, respectively). There were two decision-analytic models: the base-case scenario used 1-year follow-up data from the RCT; and a sensitivity analysis used 3-year follow-up data. Resource use was primarily drawn from this RCT. Health-related quality-of-life (HR-QOL) estimates were drawn from a UK cohort study. Both models evaluated the incremental costs and outcomes of bivalirudin compared with heparin plus GPI for patients with STEMI intended for PPCI. The analysis adopted a UK NHS perspective over a lifetime horizon. Unit costs were based on year 2009-2010 prices. The model adopted a decision-tree structure to reflect initial events for the initial period (stroke, repeat MI, minor/major bleeding events, repeat revascularization and death) and a two-state Markov component to simulate longer-term survival. The economic analysis suggested that bivalirudin is expected to dominate the heparin plus GPI strategy. This finding was consistent across the probabilistic sensitivity analysis and the vast majority of deterministic sensitivity analyses undertaken. Three exceptions to this finding were observed for the following sensitivity analyses: (1) the exclusive use of eptifibatide as the GPI (incremental cost-effectiveness ratio [ICER]=£1,764); (2) the combination of 100% eptifibatide use, 100% radial arterial access and no differential length between strategies for initial hospital stay (ICER=£4,106); and (3) a longer length of ward stay (increase of 0.33days) for the initial hospitalization (ICER=£415). The Appraisal Committee (AC) gave a positive recommendation for bivalirudin for the treatment of adults with STEMI undergoing PPCI.

Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb-IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb-IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb-IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0-2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0-1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31-6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63-9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.

THE IMPACT OF WORSENING RENAL DYSFUNCTION ON THE COMPARATIVE EFFICACY OF BIVALIRUDIN AND PLATELET GLYCOPROTEIN IIBIIIA INHIBITORS: INSIGHTS FROM BLUE CROSS BLUE SHIELD OF MICHIGAN CARDIOVASCULAR CONSORTIUM (BMC2)

To evaluate the impact of worsening renal function on the comparative bleeding risk associated with use of bivalirudin versus GP IIbIIIa inhibitors (GPI) in patients undergoing percutaneous coronary intervention (PCI). Use of bivalirudin has been associated with a reduction in the incidence of

Circulation: Cardiovascular Interventions Editors’ Picks

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Kidney Dysfunction and Long-Term Outcome in Post-PCI Acute Coronary Syndrome Patients Treated by High-Dose Tirofiban: The Role of Creatinine Clearance

Aims: Few data exist on kidney dysfunction (KD) and glycoprotein IIb/IIIa inhibitors (GPI) in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) and whether they impact on long-term outcome since most frequently patients with various degrees of KD are excluded. Study Design: Comparison of independent but concomitant arms of a randomized investigation on GPI.

025: Impact of initial clinical presentation on clopidogrel low response: is there any intra-individual variability over time?

Clopidogrel low response correlates with poor prognosis after percutaneous coronary intervention (PCI). It is today clearly demonstrated that there is a large inter-individual variability in clopidogrel response. Some authors also suggest intra-individual variability over time. We assessed the impact of initial clinical presentation on clopidogrel low response. In this prospective study, clopidogrel response was assessed in 100 patients following PCI: 50 presented with acute coronary syndrome (ACS group) and 50 patients with stable coronary disease were matched 1 to 1 on age, sex, BMI and diabetes (stable group). All patients were tested between 18h and 24h after a 600mg clopidogrel loading dose using the test of VerifyNow-P2Y12 (results expressed as PRU). Patients under chronic clopidogrel therapy or treated with GpIIb-IIIa inhibitors were excluded. The mean age was 61±12 in each group. Altogether, 28% patients were diabetics in each group and the mean BMI was 27.6±5.6 and 27.9±5.9 in the ACS group and stable group, respectively (p=ns). The mean PRU values were 159±94 and 197±80 in the ACS group and stable group, respectively (p=0.033). By multivariate analysis, “ACS group” was significantly associated with higher PRU value (p=0.018) (see Table). The present study suggests - firstly - that initial clinical presentation (especially ACS) is a strong predictor of clopidogrel low response - and secondly - an intra-individual variability over time. These results are in accordance with recent trials showing a benefit of increased antiplatelet therapy in ACS patients. Table – Predictors of clopidogrel low response. Categorical Variables Continuous Variables Univariate analysis Multivariate analysis mean PRU Correlation r p p Clinical Présentation Stable group 159 0,033 0,018 ACS group 197 Age 0,283 0,004 0,076 Sex Male 202 0,068 0,207 Female 167 BMI 0,215 0,033 0,026 Tabac No 155 0,005 0,536 Yes 205 Diabetes No 205 0,060 0,684 Yes 167 Renal failure No 174 0,182 0,775 Yes 216 PPI No 202 0,075 0,418 Yes 167

A systematic evaluation of laboratory testing for drug‐induced immune thrombocytopenia

Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. We developed a grading system to evaluate the quality of DITP laboratory testing. The 'DITP criteria' were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient.

Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: A meta-analysis of clinical trials

Successful reperfusion of epicardial coronary arteries does not necessarily result in actual myocardial perfusion. Local intracoronary (IC) delivery of GP IIb/IIIa inhibitors (GPI) has been proposed to achieve further clinical efficacy when compared to standard intravenous (IV) administration. However clinical trials have shown conflicting results. The aim of the present study was to compare IC with IV abciximab administration on mortality and MACEs in patients with ACS undergoing PCI. We performed a meta-analysis of all available clinical trials comparing intracoronary versus intravenous abciximab administration. At short-term analysis, incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.56; 95% CI 0.35-0.89; p=0.015). Interestingly, subgroup analysis showed that most benefit was coming from those studies with a main baseline LVEF<50% (OR=0.33 95% CI 0.18-0.59). Similarly, long-term incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.47; 95% CI 0.31-0.71; p<0.001), with most benefit coming from those studies enrolling patients with a main baseline EF<50% (OR=0.38 95% CI 0.23-0.63 p<0.001). In addition, long-term incidence of death was also lower in the IC group than in the IV group (OR=0.42; 95% CI 0.20-0.86; p=0.009). Our meta-analysis provides evidence of a net clinical benefit for intracoronary versus intravenous abciximab administration, with the highest benefit observed in high-risk ACS patients, such as those with reduced baseline LVEF.

Short-term effects of aspirin and clopidogrel on mean platelet volume among patients with acute coronary syndromes. A single-center prospective study

Mean platelet volume (MPV) has been correlated with platelet reactivity, thus its changes might be used to monitor the effects of antiplatelet therapy. However, no data have been reported on platelet remodelling after antiplatelet therapy. The aim of the current study was to investigate the short-term effects of oral antiplatelet therapy on MPV. Our population is represented by 62 consecutive patients with acute coronary syndrome (ACS), who did not receive GpIIb-IIIa inhibitors. We measured MPV before starting dual antiplatelet therapy, at day 1, day 2, and day 3-5 from starting adjunctive antiplatelet therapy. We additionally analyzed the relationship between platelet aggregation and MPV at admission by Multiplate in patients who were on chronic aspirin therapy. We observed a significant paradoxical increase in MPV, with a reduction in platelet count. We observed at all time intervals a significant inverse relationship between MPV and platelet count (T0: r = -0.44, P < 0.0001; T1: r = -0.36, P = 0.006; T2: r = -0.3, P = 0.026; T3-5: r = -0.29, P = 0.046). No relationship was observed between MPV and the extent of platelet aggregation inhibition by aspirin. This study showed a paradoxical increase in MPV after starting antiplatelet therapy. In addition, we did not observe any relationship between baseline MPV and the extent of platelet aggregation inhibition by aspirin. Thus, larger MPV does not imply higher platelet reactivity and may not be considered to monitor platelet reactivity and the efficacy of antiplatelet therapies.

English

We are reporting the case of a 64-year-old woman with acute inferior ST elevation myocardial infarction with right ventricular infarction. She underwent primary angiography which revealed total occlusion of distal right coronary artery (RCA) by thrombus. Three runs of aspiration were performed and the thrombus was aspirated from RCA without additional ballooning or stenting. Postaspiration angiography revealed normal TIMI-3 flow down with the resolution of the thrombus and a residual noncritical trombus was seen also. She was started on glycoprotein (GP) IIb-IIIa inhibitor tirofiban for 48 h. A new angiography performed on the 4th post-intervention day and TIMI-3 flow down was seen in RCA with complete disappearance of the residual thrombus. &nbsp; Key words:&nbsp;Intracoronary thrombus, acute myocardial infarction, thrombus aspiration.

Abstract 19450: Manual Thrombus Aspiration is not Associated with Reduction in Infarct Size Assessed by Delayed Enhancement MDCT

Objective: We sought to assess whether manual thrombus aspiration could reduce infarct size in patients with acute ST-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Background: The efficacy of manual thrombus aspiration during primary PCI for acute MI remains controversial. Methods: Between April 2009 and Mar 2011, 86 consecutive patients presenting with first acute STEMI (Killip≤II) within 12 hours after the symptom onset were randomized to manual thrombus aspiration (group I, N=44) or conventional PCI without thrombus aspiration (group II, N=42). The use of glycoprotein IIb/IIIa inhibitor (GPI) was left to the discretion of the operator. All patients received aspirin 300 mg and clopidogrel 600 mg before PCI and underwent delayed enhancement (DE) multi-detector computed tomography (MDCT) immediately after PCI without injection of an additional contrast media for assessment of infarct size, determined as the total volume of myocardium showing DE. DE MDCT was repeated at 2 months after PCI. The primary endpoint was infarct size reduction at 2 months. Results: Baseline clinical characteristics and angiographic findings were similar between the 2 groups. There were no differences between group I and II in symptom-to-door time, door-to-balloon time, PCI-to-MDCT time, Pre-PCI TIMI 0/1, post-PCI TIMI 3, or the use of GPI. Markers of myocardial reperfusion showed better outcome in group I but without statistical difference: ST-resolution rate &gt;70% (74% vs. 65%), myocardial blush grade 3 (88% vs. 68%), and corrected TIMI frame count &lt;28 (31% vs. 24%). Initial infarct size determined by DE MDCT and left ventricular ejection fraction (LVEF) by 2-dimensional echocardiography were similar between group I and II (17±18 mL vs. 22±23 mL and 58±11% vs. 55±10%, respectively). At 2 months, there was no difference in infarct size and left ventricular ejection fraction between the groups: 14±10 mL vs. 17±12 mL and 62±12% vs. 60±2%, respectively. No adverse cardiac events occurred in either group during the 2-month clinical follow-up. Conclusion: Manual thrombus aspiration was not associated with reduction in infarct size in patients with acute ST-elevation MI undergoing primary percutaneous coronary intervention.

Acute Coronary Syndrome in Patients with Diabetes Mellitus: Perspectives of an Interventional Cardiologist

Diabetes mellitus (DM) is well known to be a coronary artery disease risk equivalent but the cellular mechanism is not completely understood. Recently, virtual histology intravascular ultrasound has demonstrated that patients with DM tend to have a higher occurrence of vulnerable plaques as compared with patients without DM. Insulin-sensitizing agents, such as metformin, have been shown to have limited cardioprotective effects, whereas thiazolidinediones, such as rosiglitazone, have been reported to have possible deleterious effects on cardiovascular mortality in a meta-analysis; however, limited data exist. In contrast, pioglitazone has been reported to have a significant benefit in patients with type 2 DM with acute coronary syndrome (ACS). Animal and human studies have demonstrated the myocardial protective effects of incretins and hold promise in reducing the incidence of major adverse cardiac events in patients with DM. Moreover, in addition to aspirin, the early use of potent antiplatelet agents, such as prasugrel and intravenous glycoprotein IIb-IIIa inhibitors, in patients with DM presenting with ACS is crucial for reducing cardiovascular events in most patients. Thus, patients with DM deserve special attention in global risk factor reduction and development of newer therapeutic agents to improve glycemic control while minimizing or reducing cardiovascular events. This article focuses on ACS in patients with DM, the pathophysiology of "vulnerable blood" in patients with DM, and newer treatment strategies to improve outcomes in this high-risk patient population.

Bivalirudin Versus Heparin Plus a Glycoprotein IIb/IIIa Inhibitor in Patients With Non–ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment

The optimal antithrombotic therapy for patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention is not well defined. We investigated the efficacy and safety of bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. This study included 3798 clopidogrel-pretreated patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, who were randomly assigned to receive bivalirudin (n=1928) or heparin (unfractionated heparin or enoxaparin; n=1870) plus a GPI in the setting of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trials. Major end points were a composite of death, recurrent myocardial infarction or urgent target vessel revascularization (efficacy end point), major bleeding (safety end point), and the composite of death, recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding (net adverse clinical events [NACE]) at 30 days. The incidence of the efficacy end point was 10.6% (n=205) in the bivalirudin group versus 10.2% (n=191) in the heparin plus a GPI group (OR, 1.04; 95% CI, 0.85-1.27; P=0.69). The incidence of safety end point was 3.4% (n=66) in the bivalirudin group versus 6.3% (n=117) in the heparin plus a GPI group (OR, 0.54 [0.40-0.72]; P<0.001). NACE occurred in 258 patients (13.4%) in the bivalirudin group versus 275 patients (14.7%) in the heparin plus a GPI group (OR, 0.90 [0.76-1.06]; P=0.21). NACE rates were not significantly different between bivalirudin and heparin plus a GPI in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment. Although no significant difference in efficacy was seen in terms of suppression of adverse ischemic events, bivalirudin was superior to heparin plus a GPI in terms of reducing bleeding events. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158 and NCT00373451.

Early and late clinical outcome in elderly patients after revascularization with Primary Percutaneous Coronary Intervention presenting with acute ST-elevation myocardial infarction: Results from Qassim Primary Angioplasty Services (QAPAS) registry

We sought to investigate the procedural success rates, in hospital and 2 years clinical outcomes of Primary Percutaneous Coronary Intervention in patients older than 75 years presenting with acute myocardial infarction. Total of 50 patients, 75 years or older were enrolled in the retrospective data analysis. Primary end-points were procedural success, in hospital, short-term (1 month) and long-term (2 years) all cause mortality. Secondary end-points were recurrent MI, stroke, new revascularization. Mean age was 80.5 ± 5.75 years (range 75–96), 82% males, 18% females, 28 (56%) patients presented with anterior wall MI, 19 (38%) with inferior wall MI and 2 (4%) had posterior wall MI. All underwent PPCI achieving a door to balloon time of 140 ± 50 min (range 52–227 min) and CAG revealed SVD 16.5%, 2VD 29%, 3VD 54% and involvement of left main in 14.5% of cases. A total of 68 stents were deployed, mean stent length of 33.29 mm using DES in 42 patients (85.5%) and BMS in 2 patients (4%). Thirty (60%) patients received Glycoprotein IIbIIIa inhibitors. Successful recanalization of IRA was achieved in 90% of patients with 82% achieving TIMI III flow while no reflow occurred in 2 patients. Procedure related coronary artery dissection occurred in 2 patients. Mechanical complications like severe MR and severe LV dysfunction were observed in 4% and 16% of the cases, respectively. One patient had a massive fatal haemoptysis. In-hospital mortality was 18%. One-month and 2 years mortality were 2.5% (n = 1) and 11% (n = 4), respectively. Older age, Gp IIb IIIa use and higher Killip Class were associated with higher overall mortality. The incidence of recurrent MI and repeat revascularization was 4% and 7%, respectively. Our data reveal that in elderly patients primary PCI is a feasible revascularization strategy and such patients have a high in-hospital mortality and complication rates.