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Biomedical subjects

R C Becker

Publications and source records attributed to R C Becker.

At least 55 records · Page 3Linked to original sources

Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI Investigators. Thrombolysis in Myocardial Infarction.

OBJECTIVES: Women and men enrolled in the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial of unstable angina and non-Q wave myocardial infarction (MI) were evaluated to determine gender differences in characteristics and outcome. BACKGROUND: Coronary heart disease is the leading cause of death for women and men. However, the characteristics and outcome of women compared with men with unstable angina and non-Q wave MI have not been extensively studied. METHODS: The characteristics, outcomes and proportion of 497 women and 976 men with unstable angina and non-Q wave MI at the time of enrollment were compared. When these proportions were noted to be significantly different, we compared them with the 7,731-patient TIMI IIIB Registry, which represents the non-trial, screened population with these syndromes at these centers. RESULTS: For both coronary syndromes, women were older, were less frequently white, had a higher incidence of diabetes and hypertension and were receiving more cardiac medications. The 42-day rate of death and MI in TIMI IIIB was similar for women and men (7.4% vs. 7.5%). Coronary angiography revealed less severe coronary artery disease for women than for men, with absence of critical obstructions in 25% versus 16% and mean ejection fractions 62 +/- 12% versus 57 +/- 13% for women versus men (p < 0.01). Medical management failed in women as often as in men, and rates of cardiac catheterization and percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery were similar for women and men in the conservative strategy arm as well as in the invasive strategy arm. Women in the TIMI IIIB trial had proportionately more unstable angina than did men. The proportion of unstable angina and non-Q wave MI for women was similar in the trial and Registry. However, proportionately more men in the trial had non-Q wave MI than men in the Registry. CONCLUSIONS: 1) Women with each acute coronary syndrome are older than men and have more comorbidity. 2) The outcome with unstable angina and non-Q wave MI is related to severity of illness and not gender. 3) Mortality associated with revascularization for unstable angina and non-Q wave MI was similar for women and men. 4) The proportion of women and men enrolled with each acute coronary syndrome is different. These rates reflect both the prevalence of disease and selection bias owing to trial eligibility criteria and other identified factors.

Age Factors↗

Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. TIMI-5 Investigators. Thrombolysis in Myocardial Infarction.

Thrombin activity is increased in the setting of acute myocardial infarction (AMI) and has been shown to increase further after the administration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of early reocclusion after initially successful thrombolysis. To investigate potential mechanisms of thrombin formation in vivo, to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator (rt-PA), and to investigate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (B beta 1-42) in patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-5 study. This trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour with clinical outcomes revealed that increased FPA and TAT levels were associated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant markers were associated with hemorrhagic events. Late (12 to 24 hours) increases in F1.2, TAT, and B beta 1-42 may be predictive of recurrent ischemia. These results suggest that selected markers of procoagulant and fibrinogenolytic activity may be useful in predicting clinical outcomes in patients treated with thrombolytic therapy for AMI.

Antithrombin III↗

Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction (TIMI IIIB Trial)

Inflammation may play an important role in acute coronary syndromes. We studied the prognostic value of fibrinogen, an acute-phase protein directly involved in thrombotic process, measured serially in 1,473 patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis in Myocardial Infarction IIIB trial. Overall, no association was found between baseline (pretreatment) fibrinogen and in-hospital (< or = 10 days) myocardial infarction (p=0.70) and death (p=0.64); however, patients with spontaneous ischemia (p=0.004) and the combined unsatisfactory outcome of death, myocardial infarction, and spontaneous ischemia (p=0.003) had higher fibrinogen concentrations than those without these events. This association was confined to patients with unstable angina. A baseline fibrinogen concentration > or = 300 mg/dl was associated with a modest trend toward an increased risk of death, myocardial infarction, or spontaneous ischemia (odds ratio 1.61, 95% confidence interval 1.02 to 2.52; p=0.04). Elevation of fibrinogen, a readily measurable acute-phase protein, at the time of hospital admission is associated with coronary ischemic events and a poor clinical outcome in patients with unstable angina.

Angina, Unstable↗

Calcium channel antagonists in the modern era of coronary thrombolysis: benefit or detriment?

Calcium channel antagonists are among the world's most widely prescribed class of drugs and are used most often in patients with hypertension and coronary artery disease. However, in the recent past serious questions have been raised concerning their potentially detrimental effects. One area of considerable clinical importance that deserves close inspection is the role of calcium channel antagonists following coronary reperfusion. Specifically, is there benefit or detriment?

Blood Platelets↗

A composite view of cardiac rupture in the United States National Registry of Myocardial Infarction.

OBJECTIVES: This study was done to determine the incidence, timing and prevalence as a cause of death from cardiac rupture in patients with acute myocardial infarction. BACKGROUND: Several clinical trials and overview analyses have suggested that the survival benefit conferred by thrombolytic therapy may be offset by a paradoxic increase in early deaths from cardiac rupture. METHODS: Demographic, procedural and outcome data from patients with acute myocardial infarction were collected at 1,073 United States hospitals collaborating in the United States National Registry of Myocardial Infarction. RESULTS: Among the 350,755 patients enrolled, 122,243 received thrombolytic therapy. In-hospital mortality for the overall patient population, those not treated with thrombolytics (n = 228,512) and those given thrombolytics were 10.4%, 12.9% and 5.9%, respectively (p<0.001). Cardiogenic shock was the most common cause of death in each patient group. Although the incidence of cardiac rupture was low (<1.0%), it was responsible for 7.3%, 6.1% and 12.1%, respectively, of in-hospital deaths (p<0.001). Death from rupture occurred earlier in patients given thrombolytic therapy, with a clustering of events within 24 h of drug administration. Despite the early risk, death rates were comparatively low in thrombolytic-treated patients on each of the first 30 days. By multivariable analysis, thrombolytics, prior myocardial infarction, advancing age, female gender and intravenous beta-blocker use were independently associated with cardiac rupture. CONCLUSIONS: This large registry experience, including over 350,000 patients with myocardial infarction, suggests that thrombolytic therapy accelerates cardiac rupture, typically to within 24 to 48 h of treatment. The possibility that rupture represents an early hemorrhagic complication of thrombolytic therapy should be investigated.

Age Factors↗

Relation between systemic anticoagulation as determined by activated partial thromboplastin time and heparin measurements and in-hospital clinical events in unstable angina and non-Q wave myocardiaL infarction. Thrombolysis in Myocardial Ischemia III B Investigators.

Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction and antithrombotic therapy is a mainstay in the early management of these patients, the relation between measures of systemic anticoagulation and clinical events has not been defined clearly. In the Thrombolysis in Myocardial Ischemia III trial, 1473 patients with ischemic chest pain at rest evaluated within 24 hours of symptom onset were randomized to (1) tissue plasminogen activator (TPA) or placebo and (2) an early invasive or an early conservative strategy. All patients received a full complement of anti-ischemic medication, aspirin, and continuous intravenous heparin titrated to an activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times control for 72 to 96 hours. The median aPTT in all study groups exceeded the minimum threshold (45 seconds) by 24 hours and remained within the designated range during the protocol-directed heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p=not significant). Median 12-hour heparin concentrations were >0.2 U/ml in all groups; however, values <0.2 U/ml were common thereafter, particularly in TPA-treated patients. Time-dependent covariate analyses failed to identify statistically significant differences in either aPTT or heparin levels between patients with in-hospital clinical events (spontaneous ischemia, myocardial infarction, or death) and those without events (p=0.27). Furthermore, early clinical events occurred in a similar percentage of patients with optimal anticoagulation (all aPTTs >60 seconds, all heparin levels>0.2 U/ml), and those with aPTTs or heparin levels below these thresholds. Aggressive (high-intensity) anticoagulation with heparin to achieve aPTTs >2.0 times control does not appear to offer additional clinical benefit to lower levels (1.5 to 2.0 times control) among patients with unstable angina and non-Q wave myocardial infarction receiving intravenous heparin and oral aspirin. Therefore, the optimal level of anticoagulation in this common clinical setting is between 45 and 60 seconds when heparin is included in the treatment strategy. Direct plasma heparin measurement does not offer an advantage to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antischemic therapy and optimal anticoagulation (as it is currently defined) with heparin supports ongoing efforts to develop more effective antithrombotic agents.

Aged↗

Antithrombotic therapy. An abbreviated reference for clinicians.

Antithrombotic therapy is a mainstay in the treatment of patients with thromboembolic diseases of the arterial and venous circulatory systems. Continued work and investigation has provided much-needed information directly applicable to meeting high standards of patient care. The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy has been instrumental in developing guidelines. This article is a synopsis of the proposed guidelines, including recent updates and information that will likely influence future recommendations.

Clinical Trials as Topic↗

Cardiac rupture associated with thrombolytic therapy: impact of time to treatment in the Late Assessment of Thrombolytic Efficacy (LATE) study.

OBJECTIVES: This prospective ancillary study was conducted to determine the association between the time from symptom onset to treatment and cardiac rupture in patients with acute myocardial infarction. BACKGROUND: There is strong evidence that the time window for thrombolytic therapy should be extended to at least 12 h; however, many clinicians are concerned that late treatment may cause an excessive occurrence of death from cardiac rupture. Because up to 30% of patients with acute myocardial infarction arrive in the hospital > 6 h from symptom onset, resolving this issue is of paramount clinical importance. METHODS: A total of 5,711 patients with acute myocardial infarction were randomized to receive intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg over 3 h) or matching placebo, within 6 and 24 h from symptom onset. Both groups received immediate oral aspirin, and a majority of patients received intravenous heparin during the initial 48 h. RESULTS: By 35 days, 177 patients had died, with the cause of death specified as cardiac rupture (53 patients), electromechanical dissociation (42 patients) or asystole (82 patients). An additional 370 patients had died of other causes. In patients treated within 12 h, the proportion of rupture deaths in the group given rt-PA was higher than that observed in those who received placebo, but the difference was not statistically significant. In patients treated after 12 h, there was no evidence of an increased incidence of rupture with rt-PA, and the proportion of deaths due to rupture in this group was lower than that in patients given placebo. However, there was evidence of a difference between rt-PA and placebo with respect to the time that rupture became clinically manifest (treatment by time to death interaction, p = 0.03). CONCLUSIONS: This study provides unequivocal evidence that late treatment (6 to 24 h after symptom onset) with rt-PA is not associated with an increased risk of cardiac rupture. However, for reasons that are unclear, coronary thrombolysis appears to accelerate rupture events, typically to within 24 h of treatment.

Aged↗

Primary prevention of coronary heart disease in women.

Despite the fact that coronary heart (CHD) disease is the leading cause of death among postmenopausal women, research on primary prevention of CHD in women has been relatively sparse. Prevalence of CHD risk factors such as cigarette smoking and hypertension remain high among US women. Moreover, common factors unique to women including pregnancy, oophorectomy, menopause, and use of steroid hormones, appear to have an impact on CHD risk that is often poorly understood. While postmenopausal hormone therapy is increasingly recommended for the prevention of CHD, the potential impact of nonpharmacologic measures such as changes in diet, exercise, and cigarette smoking have been relatively unexplored.

Coronary Disease↗

Coronary thrombolysis in the treatment of women with acute myocardial infarction.

Coronary thrombolysis is a mainstay in the treatment of acute myocardial infarction occurring in men and women. Despite a higher in-hospital mortality that cannot be explained completely by age and comorbid illnesses, women clearly benefit. The relatively high rate of hemorrhagic complications requires further thought and investigation.

Female↗

Exploring the medical need for alternate site testing. A clinician's perspective.

The ability of the clinician to make rapid and precise decisions is the cornerstone of cost-effective patient care. Alternate site testing can provide rapid information to clinicians in emergency departments and critical care units. This can increase cost-effectiveness of treatment by shortening the length of hospital stays and reducing unnecessary treatment. Currently available alternate site coagulation methods allow for much more rapid achievement of effective and safe levels of anticoagulation. Potential alternate site methods of measurement of cardiac enzymes could reduce admissions to critical care units for chest pain and improve assessment of coronary artery reperfusion.

Anticoagulants↗

Comparison of clinical outcomes for women and men after acute myocardial infarction. The Thrombolysis in Myocardial Infarction Investigators.

OBJECTIVES: To assess differences in morbidity and mortality between men and women with acute myocardial infarction treated with thrombolytic therapy and the relation of differences to baseline patient characteristics and clinical features. DESIGN: Secondary analysis of observational findings among women and men enrolled in a clinical trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction Phase II trial. MEASUREMENTS: Recurrent infarctions and deaths were assessed. MAIN RESULTS: The 6-week mortality rate was greater for women than for men (9% compared with 4%; adjusted relative risk, 1.54; P = 0.01). Death or reinfarction occurred in 15.9% of women and 9.5% of men (adjusted relative risk, 1.33; P = 0.02). Among patients enrolled for treatment with 100 mg of recombinant tissue plasminogen activator and assigned to a conservative strategy of watchful waiting with appropriate backup, the 6-week incidence of death was 7.5% for women and 3.8% for men (P = 0.01). The 6-week incidences of death or reinfarction were 14.2% and 8.9% (P = 0.01) among women and men, respectively. CONCLUSIONS: Among patients in the Thrombolysis in Myocardial Infarction Phase II Trial, who all were diagnosed with myocardial infarction and were eligible to receive thrombolytic therapy, women had higher rates of mortality and morbidity than did men. Older age at the time of myocardial infarction and a history of diabetes accounted for much but probably not all of this difference.

Age Factors↗

Thrombolytic retreatment with tissue plasminogen activator for threatened reinfarction and thrombotic coronary reocclusion.

Following successful coronary arterial thrombolysis, thrombogenic substrate persists, increasing the risk of recurrent thrombosis, reocclusion, and reinfarction. The preferred treatment in this setting has not been established. Although many patients receive mechanical revascularization, it is conceivable that repeat thrombolysis, primarily with tissue plasminogen activator, represents the most readily available and effective alternative.

Angioplasty, Balloon, Coronary↗