Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers.

An increased loading dose of clopidogrel has been shown to provide more intense and rapid platelet inhibition (PI) than the standard 300-mg dose. However, patient variability in PI and in the timing of platelet recovery may affect efficacy during percutaneous coronary intervention and the bleeding risk of surgery. This study examined the degree of PI after a high-dose load of clopidogrel compared with standard dosing and the time course of functional recovery after the discontinuation of daily therapy.

Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS.

Aims: To assess the efficacy and safety of the achievement of the NCEP goal of LDL-C <1.8 mmol/L in elderly patients with ACS.

Methods And Results: The relationship between LDL-C at 30 days after ACS and subsequent clinical outcomes were compared among elderly patients (aged > or =70 years) vs.

Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes.

Background: Heart-type fatty acid binding protein (H-FABP) is a cytosolic protein that is released rapidly from the cardiomyocyte in response to myocardial injury. Although it has been investigated as an early marker of acute myocardial infarction, its prognostic utility in acute coronary syndromes has not been established.

Methods And Results: We measured H-FABP in 2287 patients with acute coronary syndromes from the OPUS-TIMI 16 trial.

Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy.

Objectives: The purpose of this study was to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing.

Background: Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy.

Methods: We searched PubMed and article references for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes.

Clinical trial design and patient demographics of the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study program: cardiovascular outcomes with etoricoxib versus diclofenac in patients with osteoarthritis and rheumatoid arthritis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently needed for the treatment of patients with arthritis. However, long-term use of such drugs that are cyclooxygenase-2 (COX-2) selective inhibitors has been reported to increase cardiovascular risk as compared with placebo, whereas long-term, randomized controlled trials assessing the risk of traditional NSAIDs versus placebo are lacking. The MEDAL program is designed to provide a precise estimate of the relative cardiovascular event rates with the COX-2 selective inhibitor etoricoxib in comparison to the traditional NSAID diclofenac in patients with osteoarthritis and rheumatoid arthritis.

Update on lipid-lowering therapy and LDL-cholesterol targets.

Serum cholesterol has long been recognized as an important risk factor for the development and progression of atherosclerotic vascular disease. For more than 30 years, improved outcomes with lipid lowering have been demonstrated. As a result of these data, the National Heart, Lung, and Blood Institute (NHLBI) convened the National Cholesterol Education Program-Adult Treatment Panel I (NCEP ATP I).

Angiographically evident thrombus following fibrinolytic therapy is associated with impaired myocardial perfusion in STEMI: a CLARITY-TIMI 28 substudy.

Aims: The presence of residual thrombus following fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) may predispose to greater embolization and microvascular dysfunction.

Methods And Results: We hypothesized that even in the presence of a patent epicardial artery, residual thrombus would be associated with worsened TIMI myocardial perfusion grades (TMPG), independent of epicardial flow. Data were analysed from the angiograms of 2684 patients enrolled in the CLARITY-TIMI 28 trial, with angiographically patent arteries (TIMI 2/3 flow) at a median of 88 h following fibrinolytic therapy.

Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery.

Objectives: We sought to characterize patterns of clopidogrel use before coronary artery bypass grafting (CABG) and examine the drug's impact on risks for postoperative transfusions among patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS).

Background: Adherence in community practice to American College of Cardiology/American Heart Association guidelines for clopidogrel use among NSTE ACS patients has not been previously characterized.

Methods: We evaluated 2,858 NSTE ACS patients undergoing CABG at 264 hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Initiative.

The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI 28 Study.

Objectives: This study was designed to determine the relationship between clopidogrel and early ST-segment resolution (STRes) and the interaction of the two with clinical outcomes after fibrinolysis.

Background: ST-segment resolution is an early noninvasive marker of coronary reperfusion.

Methods: The CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus placebo.

Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy.

Background: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored.

Methods: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE.

Results: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.

Association of platelet counts on presentation and clinical outcomes in ST-elevation myocardial infarction (from the TIMI Trials).

Platelet activation and aggregation play pivotal roles in the thrombotic process of acute coronary syndromes. However, data regarding platelet count and its association with clinical outcomes in the setting of ST-elevation myocardial infarction (STEMI) are limited. We hypothesized that higher platelet counts on presentation would be associated with poorer clinical outcomes.

Intensive statin therapy and the risk of hospitalization for heart failure after an acute coronary syndrome in the PROVE IT-TIMI 22 study.

Objectives: We aimed to determine whether intensive statin therapy reduces hospitalization for heart failure (HF) in high-risk patients.

Background: While the relationship between intensive statin therapy and ischemic events is well established, its relationship to the risk of HF after an acute coronary syndrome (ACS) is not well defined.

Methods: The Pravastatin or Atorvastatin Evaluation and Infection Trial-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study randomized 4,162 patients, stabilized after ACS, to either intensive statin therapy (atorvastatin 80 mg) or moderate statin therapy (pravastatin 40 mg).

Association between blood glucose and long-term mortality in patients with acute coronary syndromes in the OPUS-TIMI 16 trial.

Hyperglycemia in the context of acute coronary syndrome (ACS) is a common observation, and existing data suggest that high glucose levels are associated with increased in-hospital mortality. We assessed the relation between random glucose and long-term mortality in 9,020 patients with ACS who were enrolled in the OPUS-TIMI 16 trial. A significant relation between glucose level and 10-month mortality was observed (2.

Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors.

Rimonabant is a first selective blocker of the cannabinoid receptor type 1 (CB1) being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. In four large trials, after one year of treatment, rimonabant 20 mg led to greater weight loss and reduction in waist circumference compared with placebo. Therapy with rimonabant is also associated with favorable changes in serum lipid levels and an improvement in glycemic control in prediabetes patients and in type 2 diabetic patients.

Association of a history of systemic hypertension with mortality, thrombotic, and bleeding complications following non-ST-segment elevation acute coronary syndrome.

Chronic hypertension is a well established risk factor for the development of cardiovascular disease; however, its prognostic significance after a non-ST-segment elevation acute coronary syndrome remains to be established. Data from 15,414 patients included in six randomized Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 3B, TIMI 11A, TIMI 11B, TIMI 12, the Orbofiban in Patients With Unstable Coronary Syndromes [OPUS]-TIMI 16, and the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy [TACTICS]-TIMI 18) were analyzed. A history of hypertension was present in 10,998 (71.

A point-of-care assay to measure platelet aggregation in patients taking clopidogrel.

Clopidogrel is an important component of medical therapy for patients with acute coronary syndromes and those receiving coronary stents. Despite the use of clopidogrel, a significant number of patients experience recurrent adverse ischemic events. Inter-individual variability of platelet aggregation in response to clopidogrel may provide an explanation for some of these recurrent events, and small trials have linked clopidogrel resistance, as measured by platelet function tests, to adverse events.

Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial.

Background: It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS).

Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: impact of age (a meta-analysis of a decade of trials).

Background: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age.

Methods: We performed a meta-analysis of 11 published (1992-2001) randomized clinical trials of fibrinolysis in STEMI (sample size >or=3,000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005.

Clopidogrel to treat patients with non-ST-segment elevation acute coronary syndromes after hospital discharge.

Background: Clopidogrel added to aspirin improved outcomes after hospitalization in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, regardless of in-hospital treatment approach. The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for treating NSTE ACS thus recommend prescribing clopidogrel plus aspirin at discharge for all patients, not just for those undergoing percutaneous coronary intervention (PCI).

Methods: We studied 61 052 patients with high-risk NSTE ACS (defined as the presence of positive cardiac markers and/or ischemic ST-segment changes) from January 2002 through December 2003 at 461 US hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative.

Lipoprotein-associated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with the risk of cardiovascular (CV) events in population-based studies. The prognostic value of Lp-PLA2 in patients with acute coronary syndromes (ACS) has not been established.

Methods And Results: Plasma levels of Lp-PLA2 activity were measured at baseline (n=3648) and 30 days (n=3265) in patients randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial.

A tale of two trials: a comparison of the post-acute coronary syndrome lipid-lowering trials A to Z and PROVE IT-TIMI 22.

Background: The Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trials compared intensive and moderate statin therapy after acute coronary syndromes, with seemingly disparate results. We analyzed the design, implementation, and results of the two trials in an attempt to clarify the effects of early intensive statin therapy.

Methods And Results: Study design, end points, and definitions were compared.

Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors.

Rimonabant is the first selective blocker of the cannabinoid CB1 receptors being developed for the treatment of obesity, tobacco smoking and cardiometabolic risk factors. Following 1 year of treatment, rimonabant 20 mg/day leads to greater weight loss compared with placebo. Therapy with rimonabant is also associated with favourable changes in serum lipids and an improvement in glycaemic control in Type 2 diabetics.

The endocannabinoid system: a new approach to control cardiovascular disease.

The endocannabinoid (EC) system consists of 2 types of G-protein-coupled cannabinoid receptors--cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2)--and their natural ligands. The EC system plays a key role in the regulation of food intake and fat accumulation, as well as glucose and lipid metabolism. When overactivated, the EC system triggers dyslipidemia, thrombotic and inflammatory states, and insulin resistance.

Predicting a late positive serum troponin in initially troponin-negative patients with non-ST-elevation acute coronary syndrome: clinical predictors and validated risk score results from the TIMI IIIB and GUSTO IIA studies.

Background: Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker.

Methods: Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative.

Risk factors for stroke after acute coronary syndromes in the Orbofiban in Patients with Unstable Coronary Syndromes--Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study.

Background: Previous reports have associated acute coronary syndromes (ACSs) with cerebrovascular disease but in general have not included long-term patient follow-up or have not analyzed ischemic and hemorrhagic cerebrovascular events separately.

Methods: We analyzed stroke outcomes from the OPUS-TIMI 16 study, a multicenter, randomized, placebo-controlled trial. Patients were randomized to aspirin plus either orbofiban or placebo and followed for up to 1 year.