Platelet Glycoprotein IIb/IIIa Receptor Inhibition in Non-ST-Elevation Acute Coronary Syndromes

BACKGROUND: Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. METHODS AND RESULTS: We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. CONCLUSIONS: There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention

Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: Results in 16,521 patients

Objectives. We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. Background. Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately quantified, partly because of small sample sizes and methodologic limitations in previous studies. Methods. We examined the clinical and angiographic outcomes of 16,521 patients with an acute inferior myocardial infarction who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) study. Patients were classified into those without precordial ST segment depression (n = 6,422 [38.9%]), those with ST segment depression in leads V1 to V3 only (n = 5,850 [35.4%]), those with ST segment depression in leads V4 to V6 only (n = 876 [5.3%]) and those with ST segment depression in both leads V1 to V3 and leads V4 to V6 (n = 3,373 [20.4%]) on initial electrocardiography. Outcome measures included postinfarction complications (second- or third-degree heart block, congestive heart failure or shock) and 30-day and 1-year mortality. Results. Patients with precordial ST segment depression had larger infarctions, more postinfarction complications and a higher mortality rate than those without precordial ST segment depression (4.7% vs. 3.2% at 30 days; 5.0% vs. 3.4% at 1 year; both p < 0.001), regardless of whether ST segment depression was noted in leads V1 to V6 or in leads V4 to V6. The magnitude of precordial ST segment depression (sum of leads V1 to V6) added significant independent prognostic information after adjustment for clinical risk factors; the risk of 30-day mortality increased by 36% for every 0.5 mV of precordial ST segment depression. Conclusions. Assessment of the magnitude of precordial ST segment depression is useful for acute risk stratification in patients with an inferior myocardial infarction

Characteristics, treatment and outcome of patients with non-ST-elevation acute coronary syndromes and multivessel coronary artery disease: observations from PURSUIT (Platelet Glycoprotein IIb/IIIa in unstable angina: receptor suppression using integreling therapy)

BACKGROUND: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). METHODS: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving >/=1 coronary stents were separated from those in whom no stents were used. RESULTS: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. CONCLUSIONS: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients

Risk Factors for In-hospital Nonhemorrhagic Stroke in Patients With Acute Myocardial Infarction Treated With Thrombolysis: Results from GUSTO-I

BACKGROUND: Nonhemorrhagic stroke occurs in 0.1% to 1.3% of patients with acute myocardial infarction who are treated with thrombolysis, with substantial associated mortality and morbidity. Little is known about the risk factors for its occurrence. METHODS AND RESULTS: We studied the 247 patients with nonhemorrhagic stroke who were randomly assigned to one of four thrombolytic regimens within 6 hours of symptom onset in the GUSTO-I trial. We assessed the univariable and multivariable baseline risk factors for nonhemorrhagic stroke and created a scoring nomogram from the baseline multivariable modeling. We used time-dependent Cox modeling to determine multivariable in-hospital predictors of nonhemorrhagic stroke. Baseline and in-hospital predictors were then combined to determine the overall predictors of nonhemorrhagic stroke. Of the 247 patients, 42 (17%) died and another 98 (40%) were disabled by 30-day follow-up. Older age was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by higher heart rate, history of stroke or transient ischemic attack, diabetes, previous angina, and history of hypertension. These factors remained statistically significant predictors in the combined model, along with worse Killip class, coronary angiography, bypass surgery, and atrial fibrillation/flutter. CONCLUSIONS: Nonhemorrhagic stroke is a serious event in patients with acute myocardial infarction who are treated with thrombolytic, antithrombin, and antiplatelet therapy. We developed a simple nomogram that can predict the risk of nonhemorrhagic stroke on the basis of baseline clinical characteristics. Prophylactic anticoagulation may be an important treatment strategy for patients with high probability for nonhemorrhagic stroke, but further study is needed

Individual risk assessment for intracranial haemorrhage during thrombolytic therapy

Thrombolytic therapy improves outcome in patients with myocardial infarction but is associated with an increased risk of intracranial haemorrhage. For some patients, this risk may outweigh the potential benefits of thrombolytic treatment. Using data from other studies, we developed a model for the assessment of an individual's risk of intracranial haemorrhage during thrombolysis. Data were available from 150 patients with documented intracranial haemorrhage and 294 matched controls. 49 patients with intracranial haemorrhage and 122 controls had been treated with streptokinase, whereas 88 cases and 148 controls had received alteplase. By multivariate analysis, four factors were identified as independent predictors of intracranial haemorrhage; age over 65 years (odds ratio 2·2 [95% Cl 1·4–3·5]), body weight below 70 kg (2·1 [1·3–3·2]), hypertension on hospital admission (2·0 [1·2–3·2]), and administration of alteplase (1·6 [1·0–2·5]). If the overall incidence of intracranial haemorrhage is assumed to be 0·75%, patients without risk factors who receive streptokinase have a 0·26% probability of intracranial haemorrhage. The risk is 0·96%, 1·32%, and 2·17% in patients with one, two, or three risk factors, respectively. We present a model for individual risk assessment that can be used easily in clinical practice

Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes

BACKGROUND: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients. METHODS AND RESULTS: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment. CONCLUSIONS: Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction

BACKGROUND. Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of pati