Improved adherence to practice guidelines yields better outcome in high-risk patients with acute coronary syndrome without ST elevation: findings from nationwide FINACS studies

OBJECTIVES: Treatment options for acute coronary syndrome (ACS) without ST elevation have evolved rapidly during the recent years, but the successful implementation of practice guidelines incorporating new treatments into practice has been challenging. In this study, we evaluate whether targeted educational intervention could improve adherence to treatment guidelines of ACS without ST elevation. DESIGN, SETTING AND SUBJECTS: A previous study, FINACS I, evaluated the treatment and outcome of 501 consecutive non-ST elevation ACS patients that were referred in early 2001 to nine hospitals, covering nearly half of the Finnish population. That study revealed poor adherence to ESC guidelines, so targeted educational intervention on optimal practice was arranged before the second study (FINACS II), which was performed in the same hospitals using the same protocol as FINACS I. FINACS II, undertaken in early 2003, evaluated 540 consecutive patients. Interventions. Targeted educational programmes on optimal practice. MAIN OUTCOME MEASURES: The use of evidence-based therapies in non-ST elevation ACS patients. In-hospital event-free (death, new myocardial infarction, refractory angina, readmission with unstable angina and transient cerebral ischaemia/stroke) survival, and event-free survival at 6 months. RESULTS: Baseline characteristics and risk markers were similar in both studies, and no significant changes in resources were seen. In 2003, the in-hospital use of statins, ACE-inhibitors, clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonists increased significantly, and in-hospital angiography was performed more often, especially in high-risk patients (59% vs. 45%, P < 0.05); waiting time also shortened (4.2 +/- 5.5 vs. 5.8 +/- 4.7 days, P < 0.01). Overall no significant change was seen in the frequency of death either in-hospital (2% vs. 4%, P = NS) or at 6 months (7% vs. 10%, P = NS) in FINACS II. However, the survival of high-risk patients improved both in-hospital (95% vs. 90%, P = 0.05) and at 6 months (89% vs. 78%, P = 0.05). CONCLUSION: In patients with non-ST elevation ACS-targeted educational interventions appeared to be associated with improved adherence to practical guidelines, which yielded a better outcome in high-risk ACS patients.     

Efficacy and safety of bivalirudin in patients receiving clopidogrel therapy after diagnostic angiography for percutaneous coronary intervention in acute coronary syndromes

Objectives : This study sought to investigate if the efficacy of bivalirudin monotherapy is similar to heparin plus GP IIb/IIIa inhibition in patients with acute coronary syndromes (ACS) treated with clopidogrel following diagnostic angiography. Background : Prior trials have demonstrated that peri‐procedural bivalirudin therapy confers similar efficacy as heparin plus GP IIb/IIIa inhibitors, while lowering the risk of bleeding complications in ACS patients undergoing percutaneous coronary intervnetions (PCI). However, the incidence of adverse ischemic events post‐PCI appeared to be higher in patients receiving bivalirudin without adequate pretreatment with clopidogrel. Methods : Using the 2004/2005 Cornell Angioplasty Registry, we evaluated 980 consecutive patients undergoing urgent PCI for UA/NSTEMI who were treated with either bivalirudin or UFH plus GP IIb/IIIa inhibitor. We excluded patients who were on chronic clopidogrel therapy or received clopidogrel pretreatment prior to angiography. All patients received a clopidogrel load (≥300‐mg dose) immediately before or after the PCI. Long‐term all‐cause mortality was obtained for 100% of patients, with a mean follow‐up of 24.6 ± 7.7 months. Results : Of the 980 study patients, 461 (47.0%) were treated with bivalirudin and 519 (53.0%) patients received UFH plus GP IIb/IIIa inhibitor. DES were used in 88% of PCI; 45% of patients presented with NSTEMI. The incidence of in‐hospital death (0.4% vs. 0.2%, P = 0.604), post‐procedural MI (6.9% vs. 5.4%, P = 0.351), and MACE including death, stroke, emergent CABG/PCI, and MI (7.6% vs. 5.8%, P = 0.304) were similar in patients treated with bivalirudin versus UFH plus GP IIb/IIIa inhibitors, respectively. The incidence of in‐hospital stent thrombosis was similar (0.7% vs. 0%, P = 0.104), while major (0.9% vs. 2.9%, P = 0.034) and minor bleeding (10.4% vs. 18.9%, P < 0.001) was reduced in the bivalirudin‐treated group. By two‐years of follow‐up, after propensity‐score adjusted multivariate Cox regression analysis, there was no significant difference in long‐term mortality between the two groups (HR 1.18; 95%CI 0.64–2.19, P = 0.598). Conclusions : In patients presenting with ACS and receiving clopidogrel treatment after angiography (before or within 30 min of PCI), peri‐procedural bivalirudin monotherapy suppresses acute and long‐term adverse events to a similar extent as does UFH plus GP IIb/IIIa inhibitors, while significantly lowering the risk of bleeding complications. © 2010 Wiley‐Liss, Inc.     

Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and glycoprotein IIb/IIIa content in patients with acute coronary syndrome

Interaction between aggregating activity of platelets and glycoprotein (GP) IIb/IIIa (fibrinogen receptor) content on their surface was investigated in patients with acute coronary syndrome (ACS). Eighty nine ACS patients were included into the study - 69 with and 20 without elevation of ST segment. Blood was collected within the first hour of admission to the clinic (1 day), and then at 3-5 and 8-12 days. All patients received standard antiaggregant therapy - acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel (ADP receptor antagonist). Platelet aggregation was analyzed at the first time point when patients had already taken ASA but not clopidogrel, and then (3-5 and 8- 12 days) upon combined therapy with both preparations. Aggregation was induced by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel effect, platelet aggregation was decreased by 54 and 40% upon its stimulation with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa content on platelet surface was determined by binding of 125I-labelled monoclonal antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1% demonstrating the stability of this parameter in each patient. Positive correlation between platelet aggregation and GP IIb/IIIa content was detected at the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP (n=57, p<0.001). However positive association between these parameters was not revealed at 3-5 and 8-12 days, when patients received not only ASA but clopidogrel as well (r from -0.054 to -0.237, p>0.05). These results indicates that variations of GP IIb/IIIa content affect platelet aggregating activity within first hours of ACS upon ASA treatment. However after saturation with clopidogrel this factor has no significant influence on platelet aggregation, at least on aggregation induced by ADP which receptor is the target of this antiaggregant. Under such conditions aggregation parameters are presumably influenced first of all by individual characteristics of clopidogrel pharmacokinetics.     

Increased platelet aggregation induced activity by anti-glycoprotein IIb/IIIa antibody in patients with acute coronary syndrome

Interaction of glycoprotein (GP) IIb/IIIa with fibrinogen is the final and key reaction in platelet aggregation. In order to evaluate GP IIb-IIIa functional activity in patients with acute coronary syndrome (ACS) we measured platelet aggregation induced by monoclonal antibody CRC54 which is directed against GP IIb/IIIa and is able to stimulate its binding with fibrinogen and subsequent aggregation. Patients with ACS were divided into 3 groups: (1) with Q-wave myocardial infarction (MI), (2) with non Q-wave MI and with unstable angina. Patients with stable angina (SA) and healthy donors formed 2 comparison groups. The level and rate of CRC54-induced aggregation measured both in the absence and in the presence of prostaglandin E(1) (PGE(1)), the inhibitor of platelet activation, in all groups of patients with ACS were > or =1.5 times higher than in SA patients and healthy donors. Observed differences in the parameters of CRC54-induced aggregation at least in the presence of PGE(1) could be caused only by increased GP IIb/IIIa fibrinogen binding ability in ACS patients, but not by differences in the level of platelet activation. In all groups of patients with ACS, but not in SA patients and healthy donors, strong correlation (r=-0.5-0.7) was observed between increased parameters of ADP-induced aggregation and aggregation stimulated by CRC54 in the presence of PGE(1). The data obtained indicated that increased of platelet aggregating capacity in ACS might be caused by changes of GP IIb/IIIa functional characteristics and not by enhancement of platelet sensitivity towards physiological agonists including ADP.     

Different patients,different outcomes: A case‐control study of spontaneous coronary artery dissection versus acute coronary syndrome

Introduction

There is progressive interest worldwide in spontaneous coronary artery dissection (SCAD). To identify a SCAD cohort and compare risk factors, presentation, and management outcomes compared to acute coronary syndrome (ACS) matched controls.

Methods

Retrospective analysis was performed from 2000 to 2015. Clinical data included a neuropsychiatric history, with management and clinical outcomes assessed at 12 months. Patients were matched on a 1:3 case‐control basis according to type of ACS. Twenty‐two SCAD patients were matched to 66 controls by ACS type (ST‐elevation myocardial infarction 45%, Non‐ST‐elevation myocardial infarction 41%, unstable angina 14%).

Results

The SCAD group were more likely female (77.3% vs 19.7%, P < 0.0001), of younger age (48.7 ± 10.7 years vs 61.3 ± 10.6 years, P < 0.0001) with no cases of diabetes (0% vs 33.3%, P = 0.002), compared to controls. SCAD patients had a high prevalence of anxiety, depression or previous neuropsychiatric history (52.4% SCAD vs 1.5% ACS, P < 0.0001). A conservative revascularization strategy with stenting was performed in a minority of SCAD patients (13.6% SCAD vs 83.3% ACS, P < 0.0001), with no significant difference in cumulative major adverse cardiac or cerebrovascular events (MACCE) of death, stroke, re‐admission, or repeat angiography rates between both groups (13.6% SCAD vs 27.3% ACS P = NS).

Conclusion

SCAD affects young females with a paucity of cardiovascular risk factors. The major risk factor for SCAD was a history of anxiety, depression, or neuropsychiatric illness. A conservative approach to SCAD revascularization led to similar MACCE when compared to ACS controls undergoing guideline revascularization at 12 months.     

Efficacy and safety of percutaneous coronary interventions in patients with non ST segment elevation acute coronary syndrome in catheterisation laboratory without on-site surgical back-up

BACKGROUND: Percutaneous coronary intervention (PCI) in patients with non ST segment elevation acute coronary syndrome (NSTEACS) is regarded as a procedure which carries a high risk of immediate and long-term adverse cardiac events. This may potentially limit the use of PCI in catheterisation laboratories which do not have on-site surgical back up. However, stents and GP IIb/IIIa receptor inhibitors improved safety of interventional procedures. AIM: To analyse the immediate and long-term outcome of patients with NSTEACS in whom PCI was performed in a catheterisation laboratory without on-site surgical back-up in. METHODS: In a cohort of 479 consecutive patients (160 with NSTEACS - group A, 319 with stable angina - group B) we analysed short and long-term clinical outcome of PCI performed in our catheterisation laboratory which is located several kilometres from a cardiac surgery department, with an effective transfer time <30 minutes. RESULTS: Stent implantation rate and the usage of GP IIb/IIIa blockers were higher in group A than in group B (61.3% vs 50.2%, p=0.04, and 17.5% vs 6.3%; p<0.001, respectively). The in- hospital outcome was similar in both groups (death: 0.6 vs 0.6%; myocardial infarction (MI): 2.5 vs 1.6%; and urgent reintervention (rePCI): 1.9 vs 1.3%, all differences NS). Acute PCI complications requiring urgent surgical operation occurred in 1 (0.6%) patient from group A and in 1 (0.3%) patient from group B (NS). Both patients were successfully transferred for cardiac surgery. During a long-term follow-up the incidence of death (2.0 vs 2.0%), MI (0.7 vs 0.7%), rePCI (21.8 vs 25.2%), CABG (1.4 vs 1.4%) or coronary rehospitalisation (5.4 vs 7.7%) was similar in both groups. The Kaplan-Meier survival and event-free curves were parallel. CONCLUSIONS: In the era of coronary stents and platelet GP IIb/IIIa receptor inhibitors the short and long-term outcome after PCI in patients with NESTACS and stable angina is similar. The early aggressive approach to patients with NESTACS is feasible and safe in a catheterisation laboratory without on-site cardiac surgery. Surgical back-up is still necessary for only few PCI complications.     

Association of glycoprotein IIb/IIIa inhibitors and long-term survival following administration during percutaneous coronary intervention for acute myocardial infarction

Objectives: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. Background: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. Methods: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. Results: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034–0.729; P = 0.018). Conclusions: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality.     

Effectiveness of glycoprotein IIb/IIIa inhibitor use during primary coronary angioplasty: results of propensity analysis using the New York State Percutaneous Coronary Intervention Reporting System

Patients undergoing primary angioplasty in clinical practice experience a higher risk for adverse events than those enrolled in clinical trials. Whether glycoprotein (GP) IIb/IIIa inhibitor use during primary angioplasty is both safe and effective in real life is unknown. Therefore, we examined the pattern of GP IIb/IIIa use and its effectiveness in a large population-based cohort of 7,321 patients who underwent primary angioplasty in New York State. Propensity analysis was used to account for the nonrandomized use of GP IIb/IIIa inhibitors. Overall, 78.5% of patients who underwent primary angioplasty received GP IIb/IIIa inhibitors. In-hospital mortality was significantly lower with GP IIb/IIIa use (3% vs 6.2%, p <0.0001) after adjustment for both propensity score (odds ratio 0.57, 95% confidence interval 0.44 to 0.74, p <0.0001) and the combination of propensity score and clinical characteristics (odds ratio 0.63, 95% confidence interval 0.45 to 0.88, p = 0.006). Patients with older age and higher Mayo Clinic Risk Score (MCRS) received GP IIb/IIIa inhibitors less often. However, stratified analysis of patients with low to moderate risk (MCRS <12) versus high risk (>or=12) demonstrated that GP IIb/IIIa use lowered risk of mortality both in low- to moderate-risk (1.39% vs 3.23%, p <0.0001) and high-risk patients (16.15% vs 22.41%, p = 0.03). In conclusion, adjunct GP IIb/IIIa inhibitor use during primary angioplasty is effective and associated with improved in-hospital survival rates.     

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients

OBJECTIVES: Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND: The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS: The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml. RESULTS: Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS: Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.     

Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. PURSUIT Investigators

OBJECTIVES: We aimed to evaluate the benefits of the glycoprotein (GP) IIb/IIIa antagonist, eptifibatide, after patients with acute coronary syndromes (ACS) were admitted to hospitals that approach revascularization for ACS through early transfer to tertiary referral centers. BACKGROUND: Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to the hospital for non-ST segment elevation ACS, is associated with a reduction in death or myocardial infarction (MI) before and during a percutaneous coronary intervention. METHODS: The outcomes of 429 patients from 153 sites in the Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, who were transferred during study drug infusion ("transfer patients"), were compared with those of 1,987 patients who either remained in the hospital at those sites or were transferred after study drug termination ("nontransfer patients"). RESULTS: The baseline characteristics of transfer and nontransfer patients were similar. Patients receiving eptifibatide were transferred less frequently than those receiving placebo (16% vs. 20%, p = 0.014). Transfer patients underwent more procedures and experienced a greater 30-day incidence of death or MI, as compared with nontransfer patients (21% vs. 12%, p = 0.001). Eptifibatide was associated with a reduction in death or MI through 30 days, independent of transfer status (2.5% absolute reduction), as well as for those transferred (5.5% absolute reduction). CONCLUSIONS: For patients with ACS admitted to community hospitals, eptifibatide is associated with a reduced need for transfer and improved clinical outcomes.     

Angiographic and clinical outcomes of bivalirudin versus heparin in patients with acute coronary syndrome undergoing percutaneous coronary intervention

BACKGROUND: Heparin with adjunctive glycoprotein IIb/IIIa platelet receptor (GP IIb/IIIa) inhibitors has demonstrated its effectiveness in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has recently been shown to be an effective alternative for patients undergoing elective PCI. OBJECTIVES: To assess the angiographic and clinical outcomes of adjunctive pharmacological strategies in a high-risk population presenting with ACS. METHODS: Of 891 consecutive PCI patients with ACS, 304 received bivalirudin (60.5% male, 68+/-11 years) and were compared with 283 who received heparin (58.7% male, 66+/-12 years). A 30-day major adverse cardiac event was defined as the occurrence of cardiac death, nonfatal myocardial infarction, urgent revascularization or major hemorrhage. RESULTS: Adjunctive GP IIb/IIIa inhibitors were used in 14.1% of the bivalirudin group and in 72.4% of the heparin group (P<0.010). The occurrence of Thrombolysis In Myocardial Infarction (TIMI) flow less than grade 3 was lower and the achievement of angiographic success was higher in the bivalirudin group than in the heparin group (5.2% versus 8.2%, 94.7% versus 89.7%, P=0.039 and P<0.010, respectively). There was no difference between groups in the incidence of bleeding events (bivalirudin 2.0% versus heparin 3.5%, P not significant) and in 30-day major adverse cardiac events (bivalirudin 8.3% versus heparin 5.7%, P=0.223). CONCLUSIONS: In the high-risk cohort undergoing PCI, bivalirudin with provisional GP IIb/IIIa inhibitors achieved better angiographic results. Although not powered to show a difference, and while acknowledging that a selection bias could have affected the data, the present study showed that bivalirudin may be as clinically effective and safe as heparin with adjunctive GP IIb/IIIa inhibitors.     

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events.

AIMS: To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status. METHODS AND RESULTS: Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30相似文献   

Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors

OBJECTIVES: The purpose of this study was to examine the in-hospital outcome and influence of glycoprotein (GP) IIb/IIIa antagonists on patients with acute coronary syndromes (ACS) across a range of renal function. BACKGROUND: Recent studies demonstrate increasing cardiovascular risk with progressive renal dysfunction. Previous studies investigating GP IIb/IIIa antagonist use have excluded patients with renal dysfunction. METHODS: Patients presenting with ACS between January 1999 and May 2000 were identified, and data on demographics, in-hospital management, and clinical events were collected using standardized definitions. Patients were stratified according to renal function assessed by calculated creatinine clearance (CrCl) at presentation. Primary outcome measures included in-hospital mortality and major bleeding events. RESULTS: Renal insufficiency was present in 312 of 889 patients. There were 40 in-hospital deaths. In non-dialysis-dependent patients, as CrCl worsened, there was a decline in utilization of routine diagnostics and therapeutics, an increase in in-hospital mortality (p = 0.002), and an increase in major bleeding (p = 0.03). Although the use of GP IIb/IIIa antagonists was associated with an increase in major bleeding (p < 0.001), there was a protective effect on in-hospital mortality (p = 0.04) after controlling for CrCl. CONCLUSIONS: Renal dysfunction is present in a substantial proportion of patients with ACS and is associated with increased in-hospital death. Although GP IIb/IIIa antagonist use in patients with ACS and renal insufficiency resulted in increased bleeding events, its administration was associated with a decreased risk of in-hospital mortality. These preliminary findings need to be confirmed in future randomized clinical trials.     

Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention: an expert consensus

Background Therapy with either low-molecular-weight heparin (LMWH) or glycoprotein (GP) IIb/IIIa receptor antagonists is of benefit to patients with acute coronary syndromes (ACSs). However, algorithms that define how LMWH may be used in patients, proceeding from medical management to intervention and in conjunction with GP IIb/IIIa inhibitors, are lacking. The objectives of this task force were to formulate recommendations based on all available data for the use of LMWH, both with and without GP IIb/IIIa receptor antagonists, and to provide seamless integration of care during the transition from medical to interventional management. Methods and Results An international task force of 14 cardiologists with extensive experience in clinical trials was convened in New York in February 2001 to address issues related to the use of LMWH in patients with non-ST-elevation ACS. Evidence from randomized trials, observational studies, and other reports was discussed, and consensus recommendations were formulated. Conclusions Substantial evidence exists that patients receiving LMWH for an ACS can safely undergo cardiac catheterization and percutaneous coronary intervention. Concerns regarding the transition of these patients from the medical service to the cardiac catheterization laboratory should therefore not impede the upstream use of LMWH. Furthermore, LMWH and GP IIb/IIIa receptor antagonists can be used safely in combination, with no apparent increase in the risk of major bleeding. Consensus algorithms for therapy are presented. (Am Heart J 2002;144:615-24.)     

The impact of GP IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction patients

The use of glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary interventions (PCI) in the acute phase of myocardial infarction (AMI) is still a matter of debate. The aim of the present study was to compare the outcomes of patients with acute ST-segment elevation myocardial infarction who underwent primary PCI and were concomitantly treated with GP IIb/IIIa inhibitors with those who were not treated with these drugs. Between January 1996 and November 2003, a total of 418 consecutive patients underwent PCI in the setting of ST-segment elevation AMI. At the operator's discretion, 287 patients were concomitantly treated with GP IIb/IIIa inhibitors and 115 patients were not. Angiographic success and final TIMI 3 flow in the infarct-related artery was achieved more frequently in patients treated with GP IIb/IIIa inhibitors (90% vs. 77%; p=0.001). The in-hospital composite endpoint of death, reinfarction and bleeding complications was significantly better in patients treated with GP IIb/IIIa inhibitors (4% vs. 12%; p=0.005). Furthermore, the adjusted 12-month survival rate was significantly better in these patients (RR: 2.99, CI: 1.29-6.9; p=0.01). Therefore, adjunctive therapy with GP IIbIIIa inhibitors during primary PCI is associated with improved short-term outcomes and one-year survival without an increased risk of bleeding.     

Use of bivalirudin during percutaneous coronary intervention in patients with diabetes mellitus: an analysis from the randomized evaluation in percutaneous coronary intervention linking angiomax to reduced clinical events (REPLACE)-2 trial

OBJECTIVES: The objective of this study was to confirm that the efficacy and safety of percutaneous coronary intervention (PCI) in diabetic patients are not compromised by a bivalirudin-based antithrombotic strategy. BACKGROUND: Previous studies have shown a survival benefit with use of platelet glycoprotein (GP) IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. The relative efficacy of these two strategies in diabetic patients has not been studied. METHODS: We evaluated the diabetic patients enrolled in the REPLACE-2 trial to assess the impact of these antithrombotic strategies on the short- and long-term outcome after PCI. RESULTS: The REPLACE-2 trial enrolled 1,624 diabetic patients and 4,368 non-diabetic patients. Compared with non-diabetic patients, diabetic patients had similar short-term outcome but higher mortality at 1 year (3.06% vs. 1.85%, p = 0.004). There was no difference in short-term or long-term ischemic events among the diabetic patients randomized to the two arms. Specifically, the 1-year mortality rate was non-significantly lower in the bivalirudin arm, suggesting no differential survival impact of the two strategies (2.3% vs. 3.9%). There was less minor bleeding in the bivalirudin arm in diabetic patients (12.6% vs. 24.4%, p < 0.001), whereas no difference was seen in the incidence of major bleeding (3.0% vs. 3.3%, p = 0.69). CONCLUSIONS: Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with provisional GP IIb/IIIa inhibitors in diabetic patients is associated with no differences in clinical outcomes at 30 days, a trend toward lesser mortality at 1 year, and a reduction in minor bleeding.     

Effect of tirofiban therapy on ST segment resolution and clinical outcomes in patients with ST segment elevated acute myocardial infarction undergoing primary angioplasty

BACKGROUND: In our study, we assessed the effect of glycoprotein (GP) IIb/IIIa receptor inhibition on microvascular flow after acute coronary occlusion using the early sum of ST segment resolution in electrocardiography. Platelets may play a major role in the dissociation of epicardial artery recanalization and tissue level reperfusion, referred to as the 'no-reflow phenomenon'. Therefore, GP IIb/IIIa receptor inhibition might improve myocardial reperfusion, distinct from its effects on epicardial patency. METHODS AND RESULTS: One hundred and fifteen patients (mean age 57.7 +/- 12.2 years, 96 males, 19 females) with < or = 12-hour acute ST segment elevation myocardial infarction who underwent successful primary percutaneous coronary intervention were retrospectively enrolled into the study. Patients were grouped according to whether they received tirofiban therapy or not. Clinical and electrocardiographic parameters were evaluated. The first sum of ST segment elevation amounts in millimeters was obtained immediately before angioplasty and the second 60 min after restoration of thrombolysis in myocardial infarction III flow. The difference between the two measurements was accepted as resolution of the sum of ST segment elevation and expressed as SigmaSTR. There were no significant differences between the groups regarding age, gender, cardiovascular risk factors, and laboratory parameters, duration from angina onset to the emergency unit, and from door to angioplasty. SigmaSTR was higher in patients who received tirofiban than in those who did not (7.2 +/- 2.8 and 4.2 +/- 2.6 mm, respectively; p < 0.001). There was a significant and positive correlation between GP IIb/IIIa inhibition and SigmaSTR (r = 0.336, p < 0.001), as well as between ejection fraction and SigmaSTR (r = 0.310, p < 0.001). GP IIb/IIIa inhibition was the only independent determinant of SigmaSTR in a multivariate linear regression model which contains 10 variables (p < 0.001). The incidence of in-hospital post-myocardial infarction refractory angina, reinfarction, and heart failure was significantly lower in the tirofiban group (p < 0.05, p < 0.05, and p < 0.05, respectively). Additionally, after 30 days, reinfarction and heart failure were lower in the tirofiban group (p < 0.05 and p < 0.05, respectively). CONCLUSIONS: It is well known that SigmaSTR determines microvascular perfusion. This study shows that GP IIb/IIIa inhibition with tirofiban is of value in preserving microvascular perfusion after restoring coronary thrombolysis in myocardial infarction III flow.     

Antiplatelet Strategies: Evaluating Their Current Role in the Setting of Acute Coronary Syndromes

Numerous clinical trials have established the value of antiplatelet therapies for acute coronary syndromes (ACS). Aspirin (ASA), thienopyridines (i.e., clopidogrel and ticlopidine) and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS and for the prevention of thrombotic complications of percutaneous coronary intervention (PCI). Clopidogrel is beneficial when administered before and after PCI, and is more effective when combined with either ASA or GP IIb/IIIa inhibitors in preventing post‐PCI complications, coronary subacute stent thrombosis, and thrombotic events in general. It is currently unclear whether a higher loading dose of clopidogrel (600 mg) is better than the standard loading dose (300 mg), how long therapy should continue, and which maintenance dose is optimal. The role of the GP IIb/IIIa antagonists in ACS is less clear due to conflicting data from several studies with different patient populations. Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high‐risk ACS patients scheduled to undergo PCI, who demonstrate non‐ST‐segment elevation myocardial infarction and elevated troponin levels. Copyright © 2008 Wiley Periodicals, Inc.     

Value of lead aVR in the detection of significant left main coronary artery stenosis in acute coronary syndrome

BACKGROUND: Electrocardiographic lead aVR is usually ignored in patients with chest pain. ST segment elevation in aVR may have diagnostic value in patients with acute coronary syndrome (ACS) and significant stenosis or obstruction of the left main coronary artery (LMCAS), especially when accompanied by ST segment elevation in lead V(1). AIM: To asses the value of lead aVR and V1 for the detection of LMCAS in patients with ACS. METHODS: The study group consisted of 150 patients (mean age 60.6+/-9.5 years, range 33-78 years) with ACS, including 46 with LMCAS and 104 without LMCAS. ECG recordings obtained on admission were compared between these two groups. RESULTS: In patients with LMCAS, ST segment elevation in lead aVR was two times more frequent than in remaining patients (69.6% vs 34.6% p=0.0001) whereas there were no differences in lead V(1). Sensitivity of ST elevation in aVR in detection of LMCAS was 69.6%, specificity - 65.4%, positive predictive value - 47.1%, and negative predictive value - 82.9%. In patients with LMCAS, ST segment depression was significantly more often present in ECG leads other than aVR (45.6% vs 23.1% p<0.01). Patients with LMCAS more often had hypertension (95.6% vs 77.9% p<0.05) and three-vessel disease (78.3% vs 31.8%, p<0.0001). CONCLUSIONS: The assessment of lead aVR in patients with ACS may indicate LMCAS. Additional analysis of lead V(1) does not improve diagnostic accuracy.     

Timing of glycoprotein IIb/IIIa inhibitor use and outcomes among patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (results from CRUSADE)

Although glycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with unstable angina and non-ST-segment elevation myocardial infarction who undergo percutaneous coronary intervention (PCI), the American College of Cardiology/American Heart Association guidelines do not specify optimal timing for their initiation. We compared patient characteristics and clinical outcomes in 30,830 patients with non-ST-segment elevation myocardial infarction included in the CRUSADE initiative (January 2001 to December 2004) who underwent PCI with upstream (>1 hour before PCI) or periprocedural use of GP IIb/IIIa inhibitors. GP IIb/IIIa inhibitors were administered upstream in 43% of patients versus periprocedurally in 57%. Time from arrival to PCI was longer for patients who received GP IIb/IIIa inhibitors upstream (median 25.6 hours) compared with periprocedurally (18.2 hours). Unadjusted incidence of in-hospital death or reinfarction was lower with upstream GP IIb/IIIa inhibitor use (3.8% vs 4.3%, p = 0.046), but after adjusting for patient and hospital characteristics, this difference was not statistically significant. Treatment with upstream GP IIb/IIIa inhibitors was associated with a lower incidence of unadjusted death or reinfarction in patients who underwent PCI <12 hours from hospital arrival. In conclusion, in this observational analysis, overall ischemic outcomes were similar between the 2 groups, but clinical trials are needed to solve the controversy over optional timing of GP IIb/IIIa inhibitor use.