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Context: High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined.Objective: To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI.Design, Setting, and Patients: Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010.Interventions: High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months.Main Outcome Measures: The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days.Results: At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001).Conclusions: Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis.Trial Registration: clinicaltrials.gov Identifier: NCT00645918. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine if restenosis is increased in mild and moderate chronic kidney disease (CKD) patients after percutaneous coronary intervention (PCI). Background: Mortality is increased in CKD after PCI. Restenosis may contribute to increased late mortality. Methods: We analyzed 11,187 patients with a creatinine <1.8 mg/dl from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial, grouped by estimated creatinine clearance (CrCl) (<60, 60 to 89, >89 ml/min). The Cox proportional hazards models investigated the association between CrCl group and death, myocardial infarction, and target vessel revascularization (TVR). Generalized estimating equation regression models determined the association between CrCl group and lesion-specific restenosis. Results: At 30 days, there was no difference in myocardial infarction, death, or TVR between the CrCl groups. At nine months, mortality was higher in the lowest CrCl group (2.2%, 1.2%, 0.8%; p < 0.001), which was no longer significant after adjusting for confounding variables. Myocardial infarction and TVR were not different between the groups. In patients undergoing protocol follow-up angiography, restenosis (>/=50%) was not increased with CKD (32%, 32%, 37%; p = 0.02). Conclusions: Mortality nine months after PCI is mildly increased in mild or moderate CKD patients. However, restenosis is not and does not account for the increased mortality. [ABSTRACT FROM AUTHOR]

Context: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) recommend early invasive management for high-risk patients, given the benefits with this approach demonstrated in randomized clinical trials.Objectives: To determine the use and predictors of early invasive management strategies (cardiac catheterization <48 hours following presentation) in high-risk patients with NSTE ACS and to examine the association of early invasive management with mortality.Design, Setting, and Patients: The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative evaluated care patterns and outcomes for 17,926 high-risk NSTE ACS patients (positive cardiac markers and/or ischemic electrocardiographic changes) based on ACC/AHA guidelines recommendations at 248 US hospitals with catheterization and revascularization facilities between March 2000 and September 2002.Main Outcome Measures: Use of early invasive management within 48 hours of presentation, predictors of early invasive management, and in-hospital mortality. Results Of the 17,926 patients analyzed, 8037 (44.8%) underwent early cardiac catheterization less than 48 hours following presentation. Predictors of early invasive management included cardiology care, younger age, lack of prior or current congestive heart failure, lack of renal insufficiency, ischemic electrocardiographic changes, positive cardiac markers, white race, and male sex. Patients treated with early invasive management were more likely to be treated with medications and interventions recommended by the ACC/AHA guidelines and had a lower risk of in-hospital mortality after adjusting for differences in clinical characteristics and after comparing propensity-matched pairs (2.5% vs 3.7%, P<.001). Conclusions An early invasive management strategy is not utilized in the majority of high-risk patients with NSTE ACS. This strategy appears to be reserved for patients without significant comorbidities and those cared for by cardiologists and is associated with a lower risk of in-hospital mortality. [ABSTRACT FROM AUTHOR]

While performance of percutaneous coronary intervention (PCI) remains the domain of specialized cardiologists, patients undergoing PCI are cared for by noninvasive cardiologists, internists, and primary care physicians. Therefore, patient care is optimized when the entire patient care team understands procedural risks and complications as well as optimum patient management before, during, and after PCI. Before PCI, patients with contrast dye allergies should be identified and pretreated with steroids and an H1-blocker. Hydration should be initiated and maintained before and after the procedure to minimize the risks for contrast nephropathy. Periprocedure, patients should be monitored clinically for evidence of ischemia. In patients with significant groin, flank, abdominal, or back pain, as well as those with decrease in hematocrit or unexplained hypotension, the diagnosis of groin or retroperitoneal hematoma should be considered and promptly evaluated. Groin tenderness, pulsatile mass, or bruit should prompt evaluation for possible femoral pseudoaneurysm or arteriovenous fistulae. After the procedure, all patients treated with coronary stents should receive aspirin plus clopidogrel. Patients who develop typical anginal symptoms between the 1st and 6th to 8th months after PCI are likely to have restenosis and can be evaluated by an imaging study or repeated catheterization. [ABSTRACT FROM AUTHOR]

The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A). [ABSTRACT FROM AUTHOR]

Objective: We sought to examine if clopidogrel treatment initiated before coronary stenting improved clinical outcomes among patients receiving aspirin and a glycoprotein (GP) IIb/IIIa inhibitor.Background: Antiplatelet therapy plays a pivotal role in contemporary percutaneous coronary interventions (PCI).Methods: Outcomes among 4,809 patients randomized to tirofiban or abciximab during PCI with stent placement were compared according to whether they received 300 mg of clopidogrel before PCI (93.1%) versus immediately after the procedure.Results: The 30-day primary composite end point (death, myocardial infarction [MI], or urgent target vessel revascularization [TVR]) was lower among clopidogrel-pretreated patients (6.6% vs. 10.4%, p = 0.009), mainly because of reduction of MI (6.0% vs. 9.5%, p = 0.012). The benefit of clopidogrel pretreatment was sustained at six months (death, MI, any TVR: 14.6% vs. 19.8%, HR = 0.71, p = 0.010), and this was due mainly to lowering of death and MI (7.8% vs. 13.0%, p = 0.001). At one year, clopidogrel pretreatment was associated with a lower mortality rate (1.7% vs. 3.6%, p = 0.011). Because clopidogrel pretreatment was not randomized, multivariable and propensity analyses were performed. After adjusting for baseline heterogeneity, clopidogrel pretreatment was an independent predictor for death or MI at 30 days (HR = 0.63, p = 0.012) and at six months (HR = 0.61, p = 0.003), and survival at one year (HR = 0.53, p = 0.044). No excess in 30-day bleeding events was noted with clopidogrel pretreatment.Conclusions: Among patients undergoing coronary stent placement with aspirin and a GP IIb/IIIa inhibitor, clopidogrel pretreatment is associated with a reduction of death and MI irrespective of the type of GP IIb/IIIa inhibitor used. [ABSTRACT FROM AUTHOR]

Background: The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population.Methods: Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days.Results: The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02).Conclusions: Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.). [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate the efficacy and safety of clopidogrel in women and men.Background: Previous analyses have shown sex-based differences in response to several antiplatelet medications. Little is known about the efficacy and safety of clopidogrel in women and men.Methods: This study performed a meta-analysis of all blinded randomized clinical trials comparing clopidogrel and placebo (CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events], CREDO [Clopidogrel for the Reduction of Events During Observation], CLARITY-TIMI 28 [Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28], COMMIT [Clopidogrel and Metoprolol in Myocardial Infarction Trial], and CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance] trials), involving a total of 79,613 patients, of whom 30% were women. The relative efficacy and safety of clopidogrel at reducing cardiovascular events (cardiovascular death, myocardial infarction [MI], or stroke) in women and men was estimated using random-effects modeling.Results: Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42).Conclusions: Clopidogrel reduces the risk of cardiovascular events in both women and men. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether either of the gene variants associated with age-related macular degeneration is associated with coronary artery disease (CAD). PATIENTS AND METHODS: This study consisted of 493 patients who underwent clinically indicated coronary angiography between June 1, 1998, and January 1, 1999. The Y402H variant of the complement factor H (CFH) gene and the A69S variant of the LOC387715 gene locus were examined by restriction fragment length polymorphism. Multiple logistic regression models were used to assess the association of CFH and LOC gene variants with CAD. Covariates with well-established associations with CAD were also evaluated. RESULTS: Seventy patients (14%) were homozygous for the histidine variant (HH) of CFH, 237 (48%) were heterozygous for the histidine variant (HY), and 186 (38%) were homozygous for the tyrosine variant (YY). Three hundred eight patients (62%) were homozygous for the alanine allele of LOC387715, 170 (34%) were heterozygous for Ala and Ser alleles, and 15 (3%) were homozygous for the serine variant. The overall association of the CFH genotype with CAD was not statistically significant (P=.08). However, some evidence (P=-.046) suggested that CAD was increased for the HH genotype compared to the homozygous wild-type YY genotype (odds ratio, 1.95; 95% confidence interval, 1.01-3.76). Male sex, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and age were other variables that demonstrated significant associations with CAD. The overall effect of the LOC genotype was not statistically significant (P=-.06). Heterozygosity for the serine variant was (P=-.02) associated with the absence of CAD vs the AS genotype (odds ratio, 0.59; confidence interval, 0.38-0.91; P=-.02). CONCLUSION: The CFH genotype may have an independent association with CAD, although our evidence did not show statistical significance. Controlling for known risk factors, the age-related macular degeneration-associated HH variant appears to be associated with CAD. The LOC387715 gene may also play a role in CAD. [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.Methods: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.Results: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).Conclusions: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.). [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the safety and efficacy of percutaneous coronary intervention (PCI) for acute myocardial infarction performed at a hospital without cardiac surgical capability with PCI performed for acute myocardial infarction at a center with on-site surgery. PATIENTS AND METHODS: We included patients with acute myocardial infarction in whom PCI was performed from March 1, 2000, through May 31, 2002, at a community hospital (Immanuel St Joseph's) without on-site surgery. The procedural success, in-hospital adverse cardiac events, and 6-month follow-up were compared with those of PCI performed for acute myocardial infarction in matched controls from January 1, 2000, through February 28, 2002, at a center with cardiac surgery (Saint Marys Hospital). RESULTS: One hundred sixty patients (and 160 matched controls) underwent PCI for acute myocardial infarction. The procedural success rate was high and similar for the 2 groups (96% vs 95%; P=.79). In-hospital mortality, Q-wave myocardial infarction, and target vessel revascularization were low and similar for the 2 groups. No patient was referred for emergency coronary artery bypass graft surgery for failed PCI. Six-month survival from all-cause mortality was 96% for the Immanuel St Joseph's group and 94% for the Saint Marys Hospital group (P=.92). Subgroup analysis of patients with primary PCI for ST-segment elevation acute myocardial infarction revealed high procedural success and low and similar rates of major cardiac adverse events in the 2 groups. CONCLUSION: This study shows that PCI for acute myocardial infarction can be performed safely and effectively in a community hospital without on-site cardiac surgery. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine the rate of adverse cardiac events in patients undergoing magnetic resonance imaging (MRI) <8 weeks after coronary stent placement.Background: The risk of coronary stent thrombosis from dislodgement due to MRI early after stent placement is not well defined. Manufacturers recommend postponing MRI studies until eight weeks after coronary stent placement.Methods: We analyzed the Mayo Clinic Rochester Percutaneous Coronary Intervention Database and examined records of 111 patients who underwent MRI <8 weeks after coronary stent placement treated with aspirin and a thienopyridine. Occurrence of death, myocardial infarction (MI), and repeat revascularization within 30 days of MRI were recorded.Results: Magnetic resonance imaging (1.5 tesla) was performed within a median of 18 days (range, 0 to 54 days) after coronary stent placement. Four noncardiac deaths occurred, and three patients had repeat revascularization procedures. Stent thrombosis did not occur (95% confidence interval, 0% to 3.3%).Conclusions: Magnetic resonance imaging <8 weeks after coronary stent placement appears to be safe, and the risk of cardiac death or MI due to stent thrombosis is low. Postponing MRI does not appear to be necessary. [ABSTRACT FROM AUTHOR]