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Objective: To investigate outcomes in patients with ST-segment elevation myocardial infarction (STEMI) after treatment with the Stentys self-apposing stent (Stentys SAS; Stentys S.A.) for bifurcation culprit lesions., Background: The nitinol, self-expanding Stentys was initially developed as a dedicated bifurcation stent. The stent facilitates a provisional strategy by accommodating its diameter to both the proximal and distal reference diameters and offering an opportunity to "disconnect" the interconnectors, opening the stent toward the side branch., Methods: The APPOSITION (a post-market registry to assess the Stentys self-expanding coronary stent in acute myocardial infarction) III study was a prospective, multicenter, international, observational study including STEMI patients undergoing primary percutaneous coronary intervention (PCI) with the Stentys SAS. Clinical endpoints were evaluated and stratified by bifurcation vs non-bifurcation culprit lesions., Results: From 965 patients included, a total of 123 (13%) were documented as having a bifurcation lesion. Target-vessel revascularization (TVR) rates were higher in the bifurcation subgroup (16.4% vs 10.0%; P=.04). Although not statistically significant, other endpoints were numerically higher in the bifurcation subgroup: major adverse cardiac events (MACE; 12.7% vs 8.8%), myocardial infarction (MI; 3.4% vs 1.8%), and definite/probable stent thrombosis (ST; 5.8% vs 3.1%). However, when postdilation was performed, clinical endpoints were similar between bifurcation and non-bifurcation lesions: MACE (8.7% vs 8.4%), MI (1.2% vs 0.7%), and definite/probable ST (3.7% vs 2.4%)., Conclusions: The use of the Stentys SAS was safe and feasible for the treatment of bifurcation lesions in the setting of primary PCI for STEMI treatment with acceptable 1-year cardiovascular event rates, which improved when postdilation was performed.

Aims: The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in the ATOLL study., Methods: The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed., Results: The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access., Conclusions: This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality., Methods: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites., Results: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80)., Conclusion: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Primary percutaneous coronary intervention (PCI) has considerably improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) when compared with thrombolytic therapy. Prognosis after primary PCI might be further improved by decreasing stent-related complications such as stent thrombosis. The STENTYS self-apposing stent has been shown to be superior compared with balloon-expandable stents with regard to stent apposition. The current prospective randomized trial was designed to evaluate whether the superior stent apposition of the STENTYS stent results in clinical outcomes that are at least noninferior to a conventional balloon-expandable stent., Methods: The APPOSITION V is a prospective, multicenter, international, single-blinded, randomized controlled trial in STEMI patients. Randomization will be performed in a 2:1 ratio between the self-apposing nitinol bare-metal STENTYS stent and the balloon-expandable bare-metal MULTI-LINK. The primary end point is defined as target vessel failure, which is a composite of cardiac death, target vessel-related recurrent myocardial infarction, or clinically driven target vessel revascularization, at 1-year follow-up. Baseline intravascular ultrasound and optical coherence tomography (OCT) substudies will be performed in 212 and 60 subjects, respectively, and a repeat angiography at 12 to 13 months will be performed in 105 subjects, including intravascular ultrasound and OCT (in the 60 OCT patients). This study is registered on ClinicalTrials.gov with number NCT01732341., Conclusion: APPOSITION V will be the first randomized trial powered on clinical end points that directly compares the STENTYS self-apposing stent with a conventional balloon-expandable stent in patients presenting with STEMI undergoing primary PCI., (Copyright © 2014. Published by Elsevier Inc.)

The history of interventional cardiology has been marked by several technologic revolutions since the late 1970s. The first key step was the use of inflatable balloon angioplasty as an alternative to CABG surgery for coronary revascularization, followed by intracoronary delivery of bare metal stent (BMS) and drug eluting stents (DES) to drastically reduce intracoronary restenosis observed with BMS. Improved stents platforms and polymers (absorbable or biocompatible) led to a dramatic reduction in the rate of late stent thrombosis. Self-expanding stents are now available to improve stent a position especially in acute myocardial infarction. The emergence of new fully bioabsorbable stents that can be combined with antiproliferative drugs is the ongoing revolution. A new generation of stents is continuously improving and likely to become the ideal stent for coronary revascularization in the near future., (© 2014 médecine/sciences – Inserm.)

The use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) in high-risk patients with acute coronary syndromes has been associated with reductions in ischemic events but increases in bleeding complications. The role of GPIs in patients who undergo primary percutaneous coronary intervention (PCI) by the transradial approach (TRA) is not well studied. The aim of this post hoc analysis from the randomized prospective Acute Myocardial Infarction Treated With Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up (ATOLL) trial was to assess the safety and efficacy of GPIs in primary PCI performed using the TRA. A total of 910 patients were enrolled in ATOLL; 522 patients (67%) underwent PCI using the TRA. Two comparative analyses were performed. First, patients who underwent PCI using the TRA who received GPIs were compared with those who did not receive GPIs. Second, patients who underwent PCI using the TRA who received GPIs were compared with those who underwent PCI using a nonradial route and received GPIs. Composite end points of net clinical benefit, ischemic outcomes, and safety consisting of bleeding and transfusion at 1 month were analyzed. A propensity score was constructed, and weight adjustment were made for variables, including but not limited to age, weight, gender, renal function, concomitant use of other medications, Killip class, and medical history, when analyzing the end points. There was no significant difference in net clinical benefit or ischemic outcomes between either TRA patients with versus without GPIs or TRA patients with GPIs versus non-TRA patients with GPIs. Additionally, there were significantly fewer major bleeding events and blood transfusions in TRA patients with GPIs compared with non-TRA patients with GPIs. In conclusion, the addition of GPIs in the setting of primary PCI using the TRA was not associated with bleeding liability. The use of GPIs with TRA was associated with safer outcomes than using GPIs with a nontransradial approach. This study was limited in that it was a nonrandomized retrospective analysis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice., Background: Major advances in PCI techniques have considerably reduced the incidence of post-procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers., Methods: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high-volume angioplasty centers. On the basis of pre-specified clinical and PCI-linked criteria, 220 patients were selected for ambulatory PCI., Results: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4-6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non-cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non-procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10(-6))., Conclusions: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization., (Copyright © 2012 Wiley Periodicals, Inc.)

Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with ST-elevation myocardial infarction., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: In primary percutaneous coronary intervention (pPCI), conflicting data exist on the relative importance of patient presentation time (time from symptom onset (SO) to first medical contact [FMC]) and transfer time (time from FMC to sheath insertion)., Objectives: To evaluate the impact of transfer time on mortality in an unselected ST-elevation myocardial infarction (STEMI) population treated with pPCI., Methods: In a well-organized urban network, using mobile intensive care units (MICU) whenever possible, the impact of transfer time on inhospital mortality was evaluated in 703 unselected consecutive STEMI patients transferred for pPCI., Results: Our STEMI population included patients with cardiogenic shock (5.3%) and out-of-hospital cardiac arrest (3.7%). Longer transfer times were found to be associated with a stepwise increase in mortality ranging from 2.99% in the first quartile (Q1) up to 8.65% in the fourth quartile (Q4) (P=0.005). This result was noted in patients presenting early (≤2h of SO, 0.96% for Q1 vs. 9.8% for Q4, P=0.006) but not in late presenters (>2h of SO, 7.00% for Q1 vs. 7.8% for Q4, P=0.85). After adjustment for confounding variables such as the severity of patients, the relationship between mortality and transfer time was no longer apparent., Conclusions: In a well-organized urban network dedicated to pPCI, including unselected STEMI patients, transfer time does not appear to be a major contributor to mortality. The relationship of transfer time to mortality seems to be dependent on presentation time and patients' clinical severity., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objectives: The effect of ionic low osmolar contrast media (ICM) and nonionic iso-osmolar CM (NICM) on acute thrombotic complications of percutaneous coronary intervention (PCI) is subject to controversies possibly related to a potential interaction with anticoagulation regimens. We sought to compare physical and morphological properties of fibrin clots made in the presence of ioxaglate (ICM), iodixanol (NICM) versus control and to evaluate the effect of four anticoagulants used in PCI., Methods and Results: Maximum platelet aggregation (MPA%), maximum elastic modulus (EM, dyne/cm(2) ) fiber density (n/10(-5) /μm(2) ), and lysis front velocity (nm/sec) of fibrin rich clot (FRC) were measured simultaneously using peripheral blood from 12 patients undergoing elective PCI. We compared the effects of adding iodixanol or ioxaglate or saline (control) to blood with enoxaparin, unfractionated heparin, fondaparinux, and bivalirudin. Iodixanol and ioxaglate led to nonsignificant reduction in MPA compared to control (33.6% ± 16.9%, 28.2% ± 18.9%, and 40.7% ± 13.9%, respectively, P = ns). Fibrin formed with iodixanol was stiffer (42.7 ± 41.9, 18.7 ± 3.7, and 15.9 ± 9 dyne/cm(2) , P < 0.01) and displayed more fibrin fibers (1089 ± 175, 260 ± 108, and 456 ± 131 n/10(-5) /μm(2) , respectively, P < 0.01) than with ioxaglate or control. This resulted in a profound reduction in the lysis front velocity (191 ± 95, 261 ± 112, and 360 ± 153 nm/sec). None of the four anticoagulants displayed any significant interaction on the effect of contrast media., Conclusions: The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention., Design: Systematic review and meta-analysis., Data Sources: Medline and Cochrane database of systematic reviews, January 1996 to May 2011., Study Selection: Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes., Data Extraction: Sample size, characteristics, and outcomes, extracted independently and analysed., Data Synthesis: 23 trials representing 30,966 patients were identified, including 10,243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11,973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13,943 patients (45.0%) received enoxaparin and 17,023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01)., Conclusion: Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.

Background: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI)., Methods and Results: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups., Conclusions: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.

Objectives: We evaluated the incidence, types, and prognostic impact of bleeding complications in a non-selected patient population with ongoing STEMI treated with aggressive antithrombotic treatment and routine radial primary PCI., Background: Bleeding complications remain frequent and deleterious in primary PCI through femoral approach., Methods: STEMI patients (n = 671) were evaluated for bleeding complications using a web-based registry (e-PARIS). In-hospital bleeding was adjudicated using the TIMI definition., Results: In this non-selected, high risk population, 6.1% had cardiogenic shock on admission, 3.9% out-of-hospital cardiac arrest. Radial access (88%) was the default strategy as was abciximab (78%). Clopidogrel loading dose ranged from 300 to 900 mg. Pre-hospital fibrinolysis was rare (7.1%). Hemodynamic support devices (IABP, ECMO, Tandem Heart) were needed in 7.0%. In-hospital TIMI Major and TIMI Major/minor bleedings occurred in 2.5 and 5.7% of the population, respectively. In-hospital and 1-year mortality rates were 5.5 and 8.2%, respectively. Patients with in-hospital TIMI Major/minor bleeding had a higher 1-year mortality rate (31.6% vs. 3.8%, P < 0.001). The most frequent bleeding site was gastro-intestinal. Radial access was a strong predictor of survival (OR 0.33; 95%CI 0.17-0.56; P = 0.002)., Conclusions: In the setting of radial primary PCI, the rates and types of bleeding complications are somewhat different from those observed with femoral primary PCI. The gastro-intestinal tract has become the most frequent site of bleeding after radial primary PCI. The use of radial access appears independently associated with survival., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: It is unknown whether the efficacy and safety of drug-eluting stents (DES) apply in patients with chronic renal failure (CRF)., Aims: To compare DES with bare metal stents (BMS) for percutaneous coronary intervention (PCI) in CRF patients., Patients and Methods: Consecutive patients treated by PCI were allocated to four groups according to type of stent used (DES versus BMS) and creatinine clearance (CrCl). CRF was defined as CrCl less than 60 mL/minute. Cardiovascular death, major adverse cardiac events (MACE, defined as cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and definite stent thrombosis (ST) were recorded at 1 year., Results: We note that 1376 consecutive patients underwent PCI with stent within 18 months: 534 (39%) and 492 (36%) patients without CRF and 224 (16%) and 126 (9%) patients with CRF were treated with BMS and DES, respectively. In the entire cohort, patients treated with DES had a higher restenosis risk profile. BMS were predominantly (87%) used for ST-segment elevation myocardial infarction. At 1 year, 6.2% had cardiovascular death, 15.8% MACE, 7.3% TLR and 1.5% ST. Cardiovascular death and MACE occurred less frequently in DES groups. The TLR rate was not significantly different in the CRF groups (BMS 9.8% vs DES 7.1%; P=0.44). No excess of ST was observed in the DES groups and use of DES was independently associated with absence of MACE and TLR., Conclusions: In patients with CRF, DES appear to be at least as effective as BMS--despite a higher restenosis risk profile--with no excess of ST at 1 year., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI., Methods: In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00718471., Findings: 910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68-1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38-0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin., Interpretation: Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI., Funding: Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Accurate estimation of bleeding risk in patients undergoing elective percutaneous coronary intervention (PCI) is difficult and not based on widely accepted scores or characteristics. We developed and validated a simple prediction model for major bleeding using the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial, which demonstrated the superior safety of enoxaparin over unfractionated heparin (UFH) in 3528 patients undergoing elective PCI., Methods and Results: Independent predictors of non-coronary artery bypass graft (CABG)-related major bleeding events were determined using stepwise multivariate logistic regression analysis from a development dataset using bootstrap resampling. These predictors were assigned an integer coefficient (risk score) proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. Female sex, use of unfractionated heparin (vs. enoxaparin), and use of a glycoprotein IIb/IIIa inhibitor (vs. nonuse) were the strongest independent predictors of bleeding. Extensive testing found that the final model performed well with bootstrap resampling in the development set (c-statistic 0.75; 95% CI: 0.70-0.82; Hosmer-Lemeshow p = 0.29), validation set (c-statistic 0.67; Hosmer-Lemeshow p = 0.12), and subgroups of high-risk patients analysed from the validation set (c-statistic ≥ 0.67)., Conclusions: Our model for evaluating the risk of non-CABG-related major bleeding in patients undergoing elective PCI identified sex, the type of antithrombin used, and glycoprotein IIb/IIIa inhibitor use as important indicators of bleeding risk, and accurately predicted the incidence of non-CABG-related major bleeding in patients undergoing elective PCI in the STEEPLE trial., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy., Methods: In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month., Results: Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 μmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p<0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p<0.0001)., Conclusion: Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.

Objectives: This study sought to determine whether the pharmacokinetic (PK) and pharmacodynamic (PD) responses to high or standard clopidogrel loading doses (LDs) differ according to CYP2C19*2 allele., Background: CYP2C19 loss-of-function alleles are associated with reduced responsiveness to standard clopidogrel doses., Methods: Young post-myocardial infarction patients heterozygous (wild type [wt]/*2, n = 43) or homozygous (*2/*2, n = 8) for the CYP2C19*2 genetic variant were matched with patients not carrying the variant (wt/wt, n = 58). All patients were randomized to a 300- or 900-mg clopidogrel LD. The relative reduction in residual platelet aggregation (RR-RPA, %) and the area under the plasma concentration time curve of active metabolite from baseline to 6 h after loading (AUC(0-6)) were compared according to both LD and CYP2C19*2 carriage., Results: The 300-mg LD led to a gene-dose effect for RR-RPA (-65.7% ± 35.9% in wt/wt vs. -48.0% ± 38.4% in wt/*2 vs. -14.6% ± 32.4% in *2/*2; overall p value = 0.003, p = 0.03 for wt/wt versus wt/*2, p = 0.04 for wt/*2 versus *2/*2) with minor effect in *2/*2 carriers. After the 900-mg LD, the effect of the CYP2C19*2 variant on platelet inhibition was fully compensated in wt/*2 carriers but not in *2/*2 carriers (-83.6% ± 25.8% in wt/wt vs.-77.2% ± 26.9% in wt/*2 vs. -29.5% ± 26.8% in *2/*2; overall p value = 0.0003, p = 0.20 for wt/wt versus wt/*2, p < 0.001 for wt/*2 versus *2/*2). A similar pattern was observed for the active metabolite AUC(0-6) according to carriage of CYP2C19*2 for both LDs. There was a significant correlation between PK and PD responses irrespective of the LD., Conclusions: Carriers of CYP2C19*2 display significantly lower responses to clopidogrel with a gene-dose effect. Clopidogrel resistance can be overcome by increasing the dose in heterozygous carriers but not in homozygous carriers. (Clopidogrel and Response Variability Investigation Study 2 [CLOVIS-2]; NCT00822666)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The precise risk/benefit of thienopyridine pretreatment and the optimal dosage and timing of a thienopyridine loading dose (LD) for patients presenting with non-ST-segment elevation (NSTE) acute coronary syndromes are still being debated. Prasugrel, a novel thienopyridine, is an appropriate drug to address this issue as it provides predictably high and rapid inhibition of platelet aggregation., Study Design: ACCOAST is a phase 3, multicenter, parallel-group, double-blind, and event-driven study designed to compare 2 prasugrel LD schedules in patients with NSTE myocardial infarction who are scheduled for coronary angiography/percutaneous coronary intervention (PCI). Approximately 4,100 patients will be randomly assigned to an initial LD of 30 mg of prasugrel after the diagnosis followed by coronary angiography with an additional dose of 30 mg of prasugrel given at the time of PCI (pretreatment) or an LD of 60 mg of prasugrel given to patients undergoing PCI at the time of the procedure (non-pretreatment). All patients undergoing PCI will receive 5 or 10 mg of prasugrel daily. The primary objective is to test the hypothesis that prasugrel pretreatment is superior to prasugrel non-pretreatment as measured by a reduction in the composite end point of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor bailout through 7 days from randomization. Key safety end points include TIMI (Thrombolysis In Myocardial Infarction) major and minor bleeding risks., Conclusions: The ACCOAST study will provide important evidence with regard to the benefits and risks of prasugrel pretreatment compared with administration of prasugrel at the time of PCI in patients with NSTE myocardial infarction., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: CABG and PCI are effective means for revascularization of patients with multi-vessel coronary artery disease, but previous studies have not focused on treatment of patients that first undergo primary PCI., Methods: Among patients enrolled in the global registry of acute coronary events (GRACE), clinical outcomes for patients presenting with STEMI treated with primary PCI were compared according to whether residual stenoses were treated medically, surgically, or with staged PCI. Clinical characteristics and data pertaining to major adverse cardiac events during hospitalization and 6 months after discharge were collected., Results: Of the 1,705 patients included, 1,345 (79%) patients were treated medically, 303 (18%) underwent staged PCI, and 57 (3.3%) underwent CABG following primary PCI. Hospital mortality was lowest among patients treated with staged PCI (Medical = 5.7%; PCI = 0.7%; CABG = 3.5%; P < 0.001 [PCI vs. Medical]), a finding that persisted after risk adjustment (Odds Ratio PCI vs. Medical 5 0.16, [0.04-0.68]; P 5 0.01). Six month postdischarge mortality likewise was lowest in the staged PCI group (Medical = 3.1%; PCI = 0.8%; CABG = 4.0%; P = 0.04 [PCI vs. Medical]). Patients revascularized surgically were rehospitalized less frequently (Medical = 20%; PCI = 19%; CABG = 6.3%; P < 0.05) and underwent fewer unscheduled procedures (Medical 5 9.8%; PCI = 10.0%; CABG = 0.0%; P < 0.02)., Conclusions: The results of this multinational registry demonstrate that hospital mortality in patients who undergo staged percutaneous revascularization of multivessel coronary disease following primary PCI is very low. Patients undergoing CABG following primary PCI are hospitalized less frequently and undergo fewer unplanned catheter-based procedures., (© 2011 Wiley-Liss, Inc.)

Objectives: The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI)., Background: Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI., Methods: Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié-Salpêtrière registry of ischemic coronary syndromes (e-PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity-weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH., Results: Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti-Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12-0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16-0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12-0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17-0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2)., Conclusions: In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley-Liss, Inc., (Copyright © 2010 Wiley-Liss, Inc.)

Background: individual response to oral antiplatelet therapy is subject to variability, and bedside monitoring offers the opportunity of individualizing therapy for stent implantation. Time and consequence of discontinuation of thienopyridine after stenting is also an unsolved issue after drug eluting stent (DES) implantation., Study Design: the ARCTIC trial is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose adjustment in suboptimal responders as compared to a more conventional strategy without monitoring and without dose adjustment to reduce the primary end point evaluated 1 year after DES implantation. At the end of the 1-year follow-up, all patients will be randomized again to test the superiority of a strategy of pursuit of dual antiplatelet therapy beyond 1 year as compared to a strategy of interruption. ARCTIC is a multicenter, prospective, open-label study with parallel arms and a double randomization. Two thousand four hundred sixty-six patients with stable angina/ischemia or non-ST-elevation Acute Coronary Syndrome undergoing percutaneous coronary intervention (PCI) with DES implantation are being enrolled. The primary end point for the 2 tested hypotheses is the time to first occurrence of all-cause mortality, nonfatal myocardial infarction, definite/probable stent thrombosis, urgent revascularization, or nonfatal stroke. Platelet function analyses will be performed at the time of PCI and repeated 2 to 4 weeks after PCI., Conclusion: ARCTIC tests the hypothesis of personalized oral antiplatelet therapy at the time of and after DES implantation. It also examines the clinical impact of thienopyridine interruption 1 year after DES implantation.

Objectives: The FINESSE-ANGIO (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events-Angiographic) study evaluated acute treatment effects on infarct-related artery (IRA) patency and angiographic correlates of coronary microcirculatory function., Background: The FINESSE trial evaluated the effects on clinical outcomes of primary percutaneous coronary intervention (PCI) facilitated with pre-catheterization laboratory administration of abciximab with half-dose reteplase (combination-facilitated group), abciximab alone (abciximab-facilitated group), or with abciximab administered immediately before the procedure (primary PCI)., Methods: The FINESSE-ANGIO substudy compared the effects of the 3 treatment strategies on patency (TIMI [Thrombolysis In Myocardial Infarction] flow grade 2/3) of the IRA at basal coronary angiography. The secondary efficacy end points were corrected TIMI frame count, percentage of patients achieving TIMI flow grade 3, and the percentage achieving myocardial blush grade 2/3 of the IRA at post-PCI angiography. All angiographies were evaluated at a central core laboratory., Results: Of the 2,452 FINESSE patients, 637 were included in the FINESSE-ANGIO substudy. Patients in the combination-facilitated group exhibited significantly higher rates of baseline IRA patency compared with the abciximab-facilitated and the primary PCI groups (76.1% vs. 43.7% and 32.7%, respectively; p < 0.0001 for both; p = 0.025 abciximab-facilitated vs. primary PCI). There were no significant differences in the post-PCI corrected TIMI frame count (17.1 ± 15.8, 17.4 ± 17.3, and 15.8 ± 14.1) or the rates of post-PCI TIMI flow grade 3 (79.8%, 77.7%, and 76.6%), myocardial blush grade 2/3 (85.6%, 79.5%, and 86.4%), respectively., Conclusions: Pre-catheterization laboratory administration of abciximab alone and especially in combination with half-dose reteplase resulted in higher rates of IRA patency at baseline coronary angiography compared with no pre-treatment. However, post-procedural angiographic and microcirculatory variables were unaffected by facilitation therapy., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to perform a meta-analysis of randomized trials that compare new P2Y(12) inhibitors with clopidogrel to determine whether they improve clinical outcomes after percutaneous intervention (PCI)., Background: Ticlopidine/clopidogrel prevents major adverse cardiac events after PCI, but no trials have shown an effect on mortality. New P2Y(12) inhibitors are more potent and evaluated in PCI. Whether they decrease mortality after PCI compared with clopidogrel is unknown., Methods: MEDLINE and Cochrane Controlled Trials Register databases were searched from January 1980 through January 2010. Randomized, placebo-controlled trials that compared new P2Y(12) antagonists with clopidogrel in PCI were selected. Data from 8 studies were evaluated and analyses performed for all randomized patients, PCI patients (any PCI), and PCI for ST-segment elevation myocardial infarction (STEMI) patients. All-cause mortality was the primary efficacy end point. Thrombolysis In Myocardial Infarction major bleeding was the primary safety end point., Results: A total of 48,599 patients were included with 94% of patients with acute coronary syndrome and 84% of patients undergoing PCI. New P2Y(12) inhibitors significantly decreased death (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.75 to 0.92, p < 0.001 for the whole cohort; OR: 0.85, 95% CI: 0.75 to 0.96, p = 0.008 for any PCI; and OR: 0.78, 95% CI: 0.66 to 0.92, p = 0.003 for PCI for STEMI). In PCI patients, new P2Y(12) inhibitors also significantly decreased major adverse cardiac events by 18% (p < 0.001) and stent thrombosis by 40% (p < 0.001). Although there was an increase in Thrombolysis In Myocardial Infarction major bleeding for any PCI (OR: 1.23, 95% CI: 1.04 to 1.46, p = 0.01), no difference was observed in PCI for STEMI (OR: 0.98, 95% CI: 0.85 to 1.13, p = 0.76), with similar outcomes in primary PCI for STEMI. Results were confirmed in sensitivity analyses that removed the largest study., Conclusions: New P2Y(12) inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for STEMI patients., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Content: Clopidogrel, one of the most commonly prescribed medications, is a prodrug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes., Objective: To define the risk of major adverse cardiovascular outcomes among carriers of 1 (≈ 26% prevalence in whites) and carriers of 2 (≈ 2% prevalence in whites) reduced-function CYP2C19 genetic variants in patients treated with clopidogrel., Data Sources and Study Selection: A literature search was conducted (January 2000-August 2010) in MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE. Genetic studies were included in which clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and in which clinical outcomes were ascertained., Data Extraction: Investigators from 9 studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and 95% confidence intervals (CIs) for specific cardiovascular outcomes by genotype., Results: Among 9685 patients (91.3% who underwent percutaneous coronary intervention and 54.5% who had an acute coronary syndrome), 863 experienced the composite end point of cardiovascular death, myocardial infarction, or stroke; and 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles. A significantly increased risk of the composite end point was evident in both carriers of 1 (HR, 1.55; 95% CI, 1.11-2.17; P = .01) and 2 (HR, 1.76; 95% CI, 1.24-2.50; P = .002) reduced-function CYP2C19 alleles, as compared with noncarriers. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of 1 (HR, 2.67; 95% CI, 1.69-4.22; P < .0001) and 2 (HR, 3.97; 95% CI, 1.75-9.02; P = .001) CYP2C19 reduced-function alleles, as compared with noncarriers., Conclusion: Among patients treated with clopidogrel for percutaneous coronary intervention, carriage of even 1 reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis.

Background: Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI., Methods: The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. 25,086 individuals with acute coronary syndromes and intended early PCI were randomly assigned to double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300-325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done with a 24 h computerised central automated voice response system. The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes. This prespecified analysis is of the 17,263 individuals who underwent PCI. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Analyses were by intention to treat, adjusted for propensity to undergo PCI. This trial is registered with ClinicalTrials.gov, number NCT00335452., Findings: 8560 patients were assigned to double-dose and 8703 to standard-dose clopidogrel (8558 and 8702 completed 30-day follow-up, respectively), and 8624 to high-dose and 8639 to low-dose aspirin (8622 and 8638 completed 30-day follow-up, respectively). Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome (330 events [3·9%] vs 392 events [4·5%]; adjusted hazard ratio 0·86, 95% CI 0·74-0·99, p=0·039) and definite stent thrombosis (58 [0·7%] vs 111 [1·3%]; 0·54 [0·39-0·74], p=0·0001). High-dose and low-dose aspirin did not differ for the primary outcome (356 [4·1%] vs 366 [4·2%]; 0·98, 0·84-1·13, p=0·76). Major bleeding was more common with double-dose than with standard-dose clopidogrel (139 [1·6%] vs 99 [1·1%]; 1·41, 1·09-1·83, p=0·009) and did not differ between high-dose and low-dose aspirin (128 [1·5%] vs 110 [1·3%]; 1·18, 0·92-1·53, p=0·20)., Interpretation: In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the standard dose. Efficacy and safety did not differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI., Funding: Sanofi-Aventis and Bristol-Myers Squibb., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: The CONNECT study compared clinician adherence to guideline-recommended secondary prevention therapies prescribed at discharge for patients hospitalized for acute coronary syndrome (ACS) in those managed initially with percutaneous coronary intervention (PCI; revascularized) and those who did not undergo revascularization., Methods: Patients aged greater than or equal to 18 years, hospitalized for a documented ST-segment elevation or non-ST-segment elevation ACS, were enrolled consecutively over 1 month at 238 sites in France., Results: Compared with revascularized patients (n=870), non-revascularized patients (n=706) were significantly older, and a greater proportion were women, had high-blood pressure, type-2 diabetes or a history of atherothrombotic or cardiac disease, but a smaller proportion had a history of coronary angioplasty. On discharge, non-revascularized patients were prescribed beta-blockers, aspirin, statins, angiotensin-converting enzyme inhibitors or adenosine diphosphate receptor antagonists less frequently than revascularized patients. An adherence score greater than or equal to 80% (at least four of the five recommended agents prescribed at discharge) was found in 96.7% of revascularized patients and 74.4% of non-revascularized patients (P<0.001)., Conclusions: Despite a similar or even higher level of cardiovascular risk, non-revascularized ACS patients were prescribed guideline-recommended secondary prevention therapy less frequently than revascularized patients., (2010 Elsevier Masson SAS. All rights reserved.)

Aims: Controversy exists regarding the early use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial provides a unique opportunity to examine early vs. late or non-use of GPIs in a large STEMI cohort treated with PCI., Methods and Results: In the APEX-AMI trial, 3969 of 5707 patients received one of three GPIs at the operator's discretion (abciximab, eptifibatide, tirofiban). Of GPI-treated patients, the median time from symptom onset to GPI administration was 180 min (25th, 75th percentile: 130, 258); 1125 received the agent prior to arriving in the catheterization laboratory [pre-sheath; GPI to sheath insertion: 37 min (16, 66)], whereas 2844 patients were treated after arrival in the catheterization laboratory [in-lab; sheath insertion to GPI: 16 min (10, 27)]. The pre-sheath use of GPIs was associated with a significantly lower hazard of 90-day mortality [adjusted hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.48-0.95, P = 0.025] and of 90-day composite of death/CHF/shock (adjusted HR 0.81, 95% CI 0.65-1.00, P = 0.054). In-hospital severe and moderate bleeding was not related to the use of GPIs., Conclusion: This retrospective analysis from a large patient cohort with acute STEMI undergoing PCI suggests that pharmacological pre-treatment of PCI with GPIs, particularly abciximab, was associated with significantly lower occurrence of 90-day clinical outcomes and supports the pre-procedural administration of GPIs in this clinical setting.

Aims: To examine the extent of delay from initial hospital presentation to fibrinolytic therapy or primary percutaneous coronary intervention (PCI), characteristics associated with prolonged delay, and changes in delay patterns over time in patients with ST-segment elevation myocardial infarction (STEMI)., Methods and Results: We analysed data from 5170 patients with STEMI enrolled in the Global Registry of Acute Coronary Events from 2003 to 2007. The median elapsed time from first hospital presentation to initiation of fibrinolysis was 30 min (interquartile range 18-60) and to primary PCI was 86 min (interquartile range 53-135). Over the years under study, there were no significant changes in delay times to treatment with either strategy. Geographic region was the strongest predictor of delay to initiation of fibrinolysis >30 min. Patient's transfer status and geographic location were strongly associated with delay to primary PCI. Patients treated in Europe were least likely to experience delay to fibrinolysis or primary PCI., Conclusion: These data suggest no improvements in delay times from hospital presentation to initiation of fibrinolysis or primary PCI during our study period. Geographic location and patient transfer were the strongest predictors of prolonged delay time, suggesting that improvements in modifiable healthcare system factors can shorten delay to reperfusion therapy even further.

Background: Percutaneous coronary intervention (PCI) with bare-metal stenting (BMS) has been reported to be associated with high rates of target-lesion revascularization (TLR) in heart transplant recipients. We aimed to assess the outcome of successful PCI with BMS or drug-eluting stenting (DES) in such patients., Methods: Ninety-four consecutive heart transplant recipients with successful PCI of de novo lesions with BMS (n = 53) or DES (n = 60) were prospectively followed-up for 3.7 +/- 2.5 years after PCI. An angiographic lesion-based analysis at 12-month follow-up and a long-term, patient-based survival analysis were performed., Results: The lesion-based analysis within 12 months after PCI showed a reduction of TLR rates with the use of DES (6.6% vs 26.4%, p < 0.01). DES were associated with better preservation of left ventricular function at this time-point. The patient-based, long-term analysis showed sustained local benefit of DES (hazard ratio 4.5 [1.4 to 14.5] for BMS vs DES), but no effect on mortality, remote-site PCI and total revascularization rates. Anti-hypertensive (hazard ratio 0.2 [0.1 to 0.5]) and aspirin (hazard ratio 0.3 [0.1 to 0.8]) therapy, and left ventricular ejection fraction (0.96 [0.94 to 0.98] per percent) were the only correlates of long-term mortality., Conclusions: Compared with BMS, DES are associated with a sustained reduction in rates of TLR and could safely be used in heart transplant recipients with coronary artery disease. Despite excellent local effects, DES use failed to reduce mortality. Anti-hypertensive and anti-platelet therapy, and left ventricular function preservation, may be considered as aims of treatment to improve long-term survival in such patients.

Aims: To determine whether changes in practice, over time, are associated with altered rates of major bleeding in acute coronary syndromes (ACS)., Methods and Results: Patients from the Global Registry of Acute Coronary Events were enrolled between 2000 and 2007. The main outcome measures were frequency of major bleeding, including haemorrhagic stroke, over time, after adjustment for patient characteristics, and impact of major bleeding on death and myocardial infarction. Of the 50 947 patients, 2.3% sustained a major bleed; almost half of these presented with ST-elevation ACS (44%, 513). Despite changes in antithrombotic therapy (increasing use of low molecular weight heparin, P < 0.0001), thienopyridines (P < 0.0001), and percutaneous coronary interventions (P < 0.0001), frequency of major bleeding for all ACS patients decreased (2.6 to 1.8%; P < 0.0001). Most decline was seen in ST-elevation ACS (2.9 to 2.1%, P = 0.02). The overall decline remained after adjustment for patient characteristics and treatments (P = 0.002, hazard ratio 0.94 per year, 95% confidence interval 0.91-0.98). Hospital characteristics were an independent predictor of bleeding (P < 0.0001). Patients who experienced major bleeding were at increased risk of death within 30 days from admission, even after adjustment for baseline variables., Conclusion: Despite increasing use of more intensive therapies, there was a decline in the rate of major bleeding associated with changes in clinical practice. However, individual hospital characteristics remain an important determinant of the frequency of major bleeding.

Objectives: The aim of this study was to assess the risk-benefit of enoxaparin (Sanofi-Aventis, Paris, France) in primary percutaneous coronary intervention (PCI)., Background: Randomized studies have demonstrated the superiority of enoxaparin over unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytics., Methods: In the FINESSE (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events) trial--a double-blind, placebo-controlled study-2,452 patients with STEMI were randomized to primary PCI or facilitated PCI with abciximab alone or with half-dose reteplase. In this prospective FINESSE substudy, centers pre-specified use of either enoxaparin (0.5 mg/kg intravenous [IV], 0.3 mg/kg subcutaneous [SC]) or UFH (40 U/kg IV, 3,000 U maximum) with PCI. A logistic-regression model and a propensity multivariate model, both adjusted for baseline variables, were used to evaluate primary safety and secondary efficacy end points for enoxaparin versus UFH., Results: Enoxaparin was administered to 759 patients and UFH to 1,693 patients. Nonintracranial Thrombolysis In Myocardial Infarction (TIMI) major/minor bleeding was not significantly different, but lower nonintracranial TIMI major bleeding was found with enoxaparin (2.6% vs. UFH 4.4%, logistic-regression adjusted odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.31 to 0.99, p = 0.045), whereas intracranial hemorrhage was similar (0.27% vs. 0.24%, adjusted OR: 1.03; 95% CI: 0.11 to 9.68, p = 0.980). Lower death, myocardial infarction, urgent revascularization, or refractory ischemia through 30 days was also associated with enoxaparin (5.3%) versus UFH (8.0%, adjusted OR: 0.47, 95% CI: 0.31 to 0.72, p = 0.0005) as was all-cause mortality through 90 days (3.8% vs. 5.6%, respectively, adjusted OR: 0.59, 95% CI: 0.35 to 0.99, p = 0.046). End points evaluating the net clinical benefit also significantly favored enoxaparin over UFH., Conclusions: Enoxaparin seems to be associated with a lower risk of cardiovascular outcomes compared with UFH in patients with STEMI undergoing primary PCI. Confirmation of these findings in a randomized study is warranted. (A Study of Abciximab and Reteplase When Administered Prior to Catheterization After a Myocardial Infarction [Finesse]; NCT00046228)., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Major bleeding significantly impacts outcomes in patients undergoing percutaneous coronary intervention (PCI). No uniform definitions exist for major and minor bleeding. Hematomas > or =5 cm at the femoral puncture site are considered major bleeding events in some trials and minor in others. Limited information is available on the incidence and clinical relevance of hematomas > or =5 cm in PCI patients., Methods: Data from the STEEPLE trial in patients undergoing elective PCI were used to assess the impact of hematomas > or =5 cm on ischemic outcomes (mortality, nonfatal myocardial infarction, or urgent target vessel revascularization) up to day 30 and all-cause 1-year mortality. Hematoma data were available for 3,342 of 3,528 patients in STEEPLE. Patients with (n = 103) and without (n = 3,239) hematomas > or =5 cm were evenly distributed across treatment groups., Results: No differences were observed in 30-day ischemic outcomes between patients with and without hematomas (5.8% vs 5.9%, respectively; P = .96). No transfusions were observed in patients with hematomas as compared with patients without hematomas (0% and 0.4%, respectively; P = .52). A greater reduction in hemoglobin was observed (pre- vs post-PCI) in patients with hematomas as compared with patients without hematomas (-0.84 vs -0.35 g/L, P < or = .001). No significant difference in all-cause 1-year mortality was observed between patients with and without hematomas (0.0% vs 1.7%, P = .98)., Conclusions: After PCI, hematomas > or =5 cm had no effect on 30-day ischemic events or 1-year mortality. Although there is no agreed classification for large hematomas, the lack of a relationship between hematomas > or =5 cm and clinical outcome after PCI justifies the classification of these hematomas as minor bleeds in STEEPLE., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition., Methods: We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours., Results: We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14)., Conclusions: Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.), (2009 Massachusetts Medical Society)

Background: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI)., Methods: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI, followed by 600 mg of clopidogrel. The primary end point was a composite of death, myocardial infarction, or ischemia-driven revascularization at 48 hours. Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point., Results: The primary end point occurred in 185 of 2654 patients receiving cangrelor (7.0%) and in 210 of 2641 patients receiving placebo (8.0%) (odds ratio in the cangrelor group, 0.87; 95% confidence interval [CI], 0.71 to 1.07; P=0.17) (modified intention-to-treat population adjusted for missing data). In the cangrelor group, as compared with the placebo group, two prespecified secondary end points were significantly reduced at 48 hours: the rate of stent thrombosis, from 0.6% to 0.2% (odds ratio, 0.31; 95% CI, 0.11 to 0.85; P=0.02), and the rate of death from any cause, from 0.7% to 0.2% (odds ratio, 0.33; 95% CI, 0.13 to 0.83; P=0.02). There was no significant difference in the rate of blood transfusion (1.0% in the cangrelor group and 0.6% in the placebo group, P=0.13), though major bleeding on one scale was increased in the cangrelor group, from 3.5% to 5.5% (P<0.001), because of more groin hematomas., Conclusions: The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point. The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group, with no significant increase in the rate of transfusion. Further study of intravenous ADP blockade with cangrelor may be warranted. (ClinicalTrials.gov number, NCT00385138.), (2009 Massachusetts Medical Society)

Objectives: Our purpose was to evaluate long-term mortality and identify factors associated with 1-year mortality in patients who underwent elective percutaneous coronary intervention (PCI)., Background: While long-term outcomes in PCI patients have been reported previously, limited data are currently available regarding the comparative long-term outcomes in PCI patients who receive enoxaparin versus intravenous unfractionated heparin (UFH)., Methods: We conducted a follow-up analysis of clinical outcomes at 1 year in patients enrolled in the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation) trial of 3,528 patients undergoing elective PCI. Patients were randomized to receive either intravenous 0.50-mg/kg or 0.75-mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure., Results: Mortality rates were 1.4%, 2.0%, and 1.5% from 1 month to 1 year, and 2.3%, 2.2%, and 1.9% from randomization to 1 year, after index PCI in patients receiving 0.50 mg/kg enoxaparin, 0.75 mg/kg enoxaparin, and UFH, respectively. Multivariate analysis identified nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio: 3.5, 95% confidence interval: 1.7 to 7.3; p < 0.001), and major bleeding within 48 h (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.5; p = 0.04) as the strongest independent risk factors for 1-year mortality., Conclusions: The 1-year mortality rates were low and comparable between patients receiving enoxaparin and UFH during elective PCI. Periprocedural ischemic or bleeding events were the strongest independent predictors of 1-year mortality. (The STEEPLE Trial; NCT00077844).

Objectives: The aim of this report was to evaluate 12-month outcomes of facilitated percutaneous coronary intervention (PCI) in the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial., Background: Treatment delays remain common for patients with primary PCI leading to studies evaluating possible benefit of "facilitated" PCI. In the FINESSE trial, no reduction in the 90-day primary ischemic end point and an increase in bleeding were observed with both facilitated approaches, although modest favorable trends were seen for some patient subgroups., Methods: A total of 2,452 patients with ST-segment elevation myocardial infarction (MI) and anticipated 1 to 4 h delay until catheterization were randomized to reduced-dose reteplase + abciximab, abciximab alone, or placebo, followed by expedited primary PCI. Placebo-treated patients received abciximab in the cath lab. One-year mortality was a pre-specified secondary end point., Results: One-year mortalities in the 3 groups noted in the preceding text were 6.3%, 7.4%, and 7.0%, respectively (p = NS), representing 1.1%, 1.9%, and 2.5% increments since the 90-day outcome (p = 0.053 for combination treatment vs. primary PCI). A favorable trend with combination treatment was seen for patients with anterior MI (p = 0.09), but no other specified groups benefited or tended to benefit. Independent baseline correlates of 1-year mortality were systolic blood pressure <100 mm Hg, prior MI, age, Killip class >1, anterior MI, body mass index < or =25 kg/m(2), heart rate >100 beats/min, and no statin use., Conclusions: These results suggest that widespread utilization of the facilitated approaches tested cannot be justified, but that high-risk patient groups such as patients with anterior MI may deserve further study. (The FINESSE trial; NCT00046228).

Background: Concern about procedure-related bleeding is a major reason for premature discontinuation of dual oral antiplatelet therapy (APT); treatment cessation is detrimental in patients with coronary artery disease (CAD), especially after drug-eluting stent (DES) placement. The nationwide REGINA survey was designed to evaluate how the interruption of dual APT is managed in the 'real world'., Methods: Physicians (2700/4581) were randomly selected to participate in a computer-assisted telephone interview. Knowledge about DES and APT was appraised by multiple-choice questions. Strategies for temporary interruption of dual APT before an invasive or surgical procedure were evaluated using 21 scenarios, including high-risk (30 days after DES) and low-risk (18 months after DES) periods., Results: Out of 2700 practitioners, 2515 completed the interview. Rates of correct answers to basic knowledge questions ranged from 0% (dentists) to 52% (cardiologists). Unjustified total interruption of dual APT was much more frequent than expected (22.0% vs. 11.8%). A strategy of total interruption was less frequently chosen in the period of high ischemic risk compared to the low-risk period (13.7% vs. 31.1%, p<0.0001). Dual APT interruption in patients who require additional invasive cardiac or surgical procedures depended on type of physician consulted (more frequent in specialists than general practitioners or dentists), and on the physician's age and practice type (rural/private vs. urban/hospital). Correct answers were more frequently given in situations bearing a major risk, either ischemic or bleeding risk, than in those with no risk (49.2% vs. 30.2%, p<0.0001). Low-molecular-weight heparin was the substitution therapy in over two-thirds of scenarios and was associated with longer periods of APT interruption., Interpretation: Adequate management of APT in patients with intracoronary stents who undergo potentially haemorrhagic invasive procedures depends mainly on the type of physician involved and their practice rather than on a carefully weighted assessment of ischemic/bleeding risk. Our findings suggest a lack of scientific evidence, insufficient knowledge of guidelines, and poor communication between physicians managing these patients.

Objectives: We hypothesized that patients most likely to benefit would be those at high risk with a shorter duration of acute ischemia and who required transfer for percutaneous coronary intervention (PCI)., Background: The FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) study failed to demonstrate an improvement in the 90-day composite clinical end point of early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or abciximab alone., Methods: We performed a retrospective analysis of 2,452 patients in this double-blind, placebo-controlled study. Patients were stratified by Thrombolysis In Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI), presentation to a spoke (no PCI available) or hub site, and symptom-to-randomization time. Outcomes included the primary composite end point of death, ventricular fibrillation after 48 h, cardiogenic shock, and congestive heart failure through day 90 as well as 1-year mortality., Results: Mortality for all patients at 1 year was directly related to TIMI risk score (23 of 1,223 = 1.9% in patients with score <3 and 145 of 1,229 = 11.8% with score > or =3, p < 0.001). Patients with TIMI risk score > or =3 and presentation to a spoke site with a symptom-to-randomization time < or =4 h had significantly better 1-year survival if treated with combination-facilitated PCI (hazard ratio [HR]: 0.351, p = 0.01) as well as 90-day composite outcome (HR: 0.45, p = 0.009). A trend for improved survival was also observed in patients with TIMI score > or =3 and spoke site alone (HR: 0.549, p = 0.06)., Conclusions: Facilitation of PCI with a combination of abciximab and half-dose reteplase improved survival at 1 year in high-risk patients presenting to a spoke hospital with symptom-to-randomization time < or =4 h. Further prospective study of facilitated PCI in this subgroup of patients is warranted.

Background: Late discontinuation of clopidogrel after an acute coronary syndrome or stent placement may be associated with a clinical rebound effect., Aims: To describe the characteristics and evolution of patients non-compliant to study drug in the prospective, randomized, double-blind CHARISMA trial., Methods: Of 15,603 patients aged 45 or older years with established atherothrombotic disease (coronary artery disease, stroke, peripheral arterial disease) or multiple cardiovascular risk factors, 2999 permanently interrupted (withdrawers) study drug (clopidogrel or placebo) during follow-up. The primary endpoint was first occurrence since randomization of myocardial infarction, stroke or cardiovascular death., Results: Withdrawers displayed a higher risk profile and rates of death/myocardial infarction/stroke (13.5% versus 5.6%; hazard ratio [HR]: 3.18; 95% confidence interval [CI]: 3.05-3.32; p<0.001) and severe bleeding (4.9% versus 0.7%; odds ratio [OR]: 7.42; 95% CI: 5.67-9.70; p<0.001) versus non-withdrawers. Death/myocardial infarction/stroke occurred after an average of 228 days (95% CI: 197-258) and was less frequent in patients assigned to clopidogrel versus placebo (9.7% versus 11.9%; HR: 0.80; 95% CI: 0.64-1.00; p=0.051); the rate of severe bleeding was the same (4.0% versus 4.3%; OR: 0.92; 95% CI: 0.65-1.32; p=0.66). Among withdrawers, initial clopidogrel treatment was an independent correlate of survival (HR: 0.74, 95% CI: 0.59-0.93; p=0.011), but not severe bleeding (OR: 0.94; 95% CI: 0.65-1.35; p=0.74). Kaplan-Meier curves for the primary endpoint suggested no rebound effect or disease reactivation after discontinuation of clopidogrel compared with placebo., Conclusions: Patients who stopped medication had increased rates of ischaemic and bleeding events and mortality. Patients initially on clopidogrel had fewer ischaemic events than those on placebo; discontinuation was not associated with any clinically detectable rebound effect.

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Objective: To evaluate the impact of sheath management on bleeding rates., Background: The procedural characteristics and anticoagulant regimen determine the frequency of postoperative bleeding complications following percutaneous coronary intervention (PCI)., Methods: This subanalysis of the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial evaluated the relative impact of enoxaparin or unfractionated heparin (UFH) on the rate of non-coronary artery bypass graft-related major and minor bleeding, according to sheath management procedures in 3,528 patients undergoing elective PCI with a femoral approach., Results: Sheaths were removed at a median time of 54 min with enoxaparin 0.5 mg/kg, compared with 3 hr 14 min with enoxaparin 0.75 mg/kg and 2 hr 24 min with UFH. Early sheath removal (within 30 min from the end of PCI) was associated with reduced bleeding in patients receiving 0.5 or 0.75 mg/kg enoxaparin compared with UFH (enoxaparin 0.5 mg/kg: 4.9% vs. 10.8%; P < 0.001; enoxaparin 0.75 mg/kg: 5.0% vs. 10.8%; P < 0.001). Compared with UFH, major and minor bleeding was halved when enoxaparin (0.5 mg/kg and 0.75 mg/kg) was used in combination with a closure device (4.4% and 5.3% vs. 10.5% with UFH) or smaller (<7 Fr) sheath sizes (4.9% and 6.0% vs. 9.3%)., Conclusion: This analysis shows that early sheath removal can be performed safely following elective PCI in patients receiving enoxaparin. Enoxaparin use was associated with less major and minor bleeding compared with UFH, when either a closure device or a smaller sheath size was used., (Copyright 2009 Wiley-Liss, Inc.)

Background: The STEEPLE trial assessed outcomes of patients undergoing elective percutaneous coronary intervention randomized to receive a bolus of intravenous enoxaparin (0.5 or 0.75 mg/kg, n = 2,298) or activated clotting time-adjusted unfractionated heparin (UFH, n = 1,230), stratified according to planned glycoprotein IIb/IIIa inhibitor use., Methods: In this subanalysis, we assessed outcomes in patients with renal impairment (creatinine clearance < or =60 mL/min, n = 659)., Results: Major bleeding occurred more often in patients with renal impairment compared with those without (2.7% vs 1.5%, P = .04). Enoxaparin was associated with less major bleeding than UFH with normal renal function (0.9% for enoxaparin 0.5 mg/kg or 1.0% for enoxaparin 0.75 mg/kg vs 2.6%, respectively; both P = .01 vs UFH), with a trend toward less major bleeding with impaired renal function (2.6% or 1.8% vs 3.8%, P = .18 for enoxaparin 0.5 mg/kg and P = .47 for 0.75 mg/kg vs UFH). Minor bleeding rates were similar irrespective of renal function or anticoagulation regimen. The incidence of death, nonfatal myocardial infarction, or urgent target-vessel revascularization was similar between patients with and without renal impairment (5.7% vs 6.5%, P = .45). In patients with renal impairment, event rates were 6.2% or 5.3% with enoxaparin vs 5.6% with UFH (P = nonsignificant). Target anticoagulation levels were achieved 4 to 5 times more often with enoxaparin compared with UFH in patients with normal and impaired renal function (both P < .0001)., Conclusions: A single bolus of enoxaparin was associated with similar ischemic events and a trend for less major bleeding compared with UFH in patients with renal impairment undergoing percutaneous coronary intervention. Enoxaparin can be administered safely without dose adjustment in these patients.

Objectives: We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day., Background: Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel., Methods: One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day., Results: After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group., Conclusions: In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).

Background: Limited information is available about clinical outcomes following routine percutaneous coronary intervention (PCI) in the current era. This study aimed to identify predictors of adverse clinical or angiographic complications following PCI in patients from many different countries., Methods: RIVIERA is a multinational, prospective, observational study in patients undergoing elective or primary PCI. Consecutive patients (n=7962) were enrolled in 144 hospitals from 23 countries in four different continents. Primary outcome was death or myocardial infarction (MI). The mean age of the patients was 59 years and 77% were men; 92% of patients underwent elective and 8% primary PCI., Results: The rate of in-hospital outcomes was low: death 0.3%, MI 1%, any bleeding 3.4%. Angiographic complications occurred in 8.7% of patients, mainly coronary dissection (3.7%) and no reflow (2%). After multivariable analysis, the strongest independent predictors of death or MI were clinical presentation with non-ST-segment elevation acute coronary syndrome or ST-segment elevation myocardial infarction and administration of a glycoprotein (GP) IIb/IIIa inhibitor. Radial access, thienopyridine pretreatment and anticoagulation with enoxaparin were associated with a lower risk of death or MI. Female gender, PCI of coronary artery bypass graft, administration of a GP IIb/IIIa inhibitor and combined use of enoxaparin and unfractionated heparin were significantly associated with more bleeding. Radial access was the only variable associated with less bleeding., Conclusions: Routine PCI appears to be a relatively safe revascularization procedure. Many of the variables identified as predictors of adverse cardiac outcomes confirm results obtained in recent randomized PCI trials and are modifiable, suggesting that further improvements can be made.