"Hot" unstable angina--is it worse than subacute unstable angina? Results from the GUARANTEE Registry.

BACKGROUND AND METHODS: Because time to presentation to the hospital affects time to treatment and is known to be important in acute myocardial infarction, we evaluated this variable in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI admitted to 35 hospitals in 6 geographic regions of the United States, we compared patients with acute (onset of pain <12 hours before admission) and subacute (onset >12 hours) unstable angina. RESULTS: Patients with "hot" (acute) unstable angina presented more often to the emergency department and were subsequently admitted more often to an intensive care unit. Hospital administration of medications did not differ between the two groups, with the exception of heparin, which was paradoxically used more often in subacute patients (p<0.001). All cardiac invasive procedures were undertaken less often in the acute patients (catheterization, 41.4% vs. 58.7%, p=0.001; percutaneous coronary intervention, 11.3% vs. 21.1%, p=0.001; coronary artery bypass grafting, 5.6% vs. 12.0%, p=0.001). A greater percentage of acute patients were found to have no significant coronary artery disease at cardiac catheterization (20.1% vs. 15.0%, p=0.006). Mortality did not differ between the two groups; however, the composite endpoint of death and MI favored the acute patients (1.3% vs. 2.2%, p=0.032). CONCLUSIONS: Contrary to our initial hypothesis, "hot" UA patients tended to be at lower risk than patients with subacute presentation, highlighting the fact that patients with UA/NSTEMI remain at high risk even after the initial 12-hour period.

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing.

BACKGROUND: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS: Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS: The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

Clinical benefit of glycoprotein IIb/IIIa blockade with Abciximab is independent of gender: pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of 7E3 for the Prevention of Ischemic Complications. Evaluation in Percutaneous Transluminal Coronary Angioplasty to Improve Long-Term Outcome with Abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stent.

OBJECTIVES: We sought to determine the efficacy and safety of platelet glycoprotein IIb/IIIa receptor (GP IIb/IIIa) blockade with abciximab in women undergoing percutaneous coronary intervention. BACKGROUND: Although gender differences in response to platelet glycoprotein IIb/IIIa receptor blockade have been described, there have been no large clinical studies to assess these differences. METHODS: Outcomes were determined using meta-analysis technique. RESULTS: In the pooled analysis, the primary end point of death, myocardial infarction (MI) or urgent revascularization within 30 days was reduced from 11.3% to 5.8% (p<0.001) in men and from 12.7% to 6.5% (p<0.001) in women treated with abciximab. At six months, death, MI or urgent revascularization was reduced from 14.1% to 8.3% (p<0.001) in men and 16.0% to 9.9% (p<0.001) in women receiving abciximab. At one year, mortality was reduced from 2.7% to 1.9% (p = 0.06) in men and 4.0% to 2.5% (p = 0.03) in women treated with abciximab. Major bleeding events occurred in 2.9% versus 3.0% (p = 0.96) of women and 2.7% versus 1.3% (p = 0.003) of men treated with placebo versus abciximab, respectively. Minor bleeding events occurred in 4.7% versus 6.7% (p = 0.01) of women and 2.3% versus 2.2% (p = 0.94) of men treated with placebo versus abciximab, respectively. CONCLUSIONS: This pooled analysis demonstrated no gender difference in protection from major adverse outcomes with GP IIb/IIIa inhibition with abciximab. Although women had higher rates of both major and minor bleeding events with abciximab compared with men, major bleeding in women was similar with and without abciximab. There was a small increased risk of minor bleeding with abciximab in women.

Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of platelet IIb/IIIa inhibitor for stenting trial) diabetic substudy.

BACKGROUND: Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. METHODS AND RESULTS: We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty-abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients (P=0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty-abciximab, and 6.2% for the stent-abciximab group (P=0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab (P=0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P=0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P=0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1. 2% for stent-abciximab patients (P=0.11). CONCLUSIONS: The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.

Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.

Racial differences in the management of unstable angina: results from the multicenter GUARANTEE registry.

BACKGROUND: Prior studies, usually conducted with the use of insurance databases, have shown differences in the use of cardiac procedures between black patients and white patients hospitalized with various types of coronary artery disease. However, few data are available in prospectively collected cohorts of patients with unstable angina or on the use of appropriate medications or interventions. METHODS AND RESULTS: We evaluated 2948 consecutive patients with unstable angina admitted to 35 hospitals across the United States in 1996, comparing nonwhite and white patients. Seventy-seven percent of patients were white, 14% were black, 4% were Hispanic, 1% were Asian, and 3% were other or unknown race. Differences were seen in coronary risk profile, with a higher incidence of hypertension and diabetes mellitus in nonwhites. Cardiac catheterization was performed less often in nonwhites compared with whites (36% vs 53%, P =.001). Even in patients meeting the criteria for appropriate catheterization in the Agency for Health Care Policy Research unstable angina guidelines, fewer nonwhites underwent catheterization (44% vs 61%, P =.001), but among these, fewer nonwhites had significant coronary stenosis (72% vs 90%, P =.001). However, among patients catheterized who had indications for revascularization, angioplasty and coronary artery bypass grafting were performed equally often in nonwhites and whites. CONCLUSIONS: Current guidelines would recommend more aggressive use of cardiac catheterization for nonwhite patients. However, our findings suggest that racial differences may need to be included in the diagnostic and interventional algorithms.

Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.

BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.

Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.

Percutaneous cardiopulmonary bypass support: a new approach to high-risk angioplasty.

Percutaneous cardiopulmonary bypass is a new technique for supporting systemic blood flow during high-risk coronary angioplasty procedures. This mechanical alternative, unlike traditional methods, is not limited by dependency on adequate left ventricular stroke volume. Percutaneous cardiopulmonary bypass support offers new and demanding challenges in the care of this high-risk group of patients.

Characterization of the covalent mercury (II)-NADPH complex.

Mercury (II) forms a covalent, 1:1 complex with NADPH which is indicated by the disappearance of the chromophore at 340 nm. With the use of NMNH as an analogue, the spectral changes were attributed to the reaction of Hg(II) with the nicotinamide ring. This reaction is reversed by the addition of sulfhydryl groups or other metal-chelating agents. The structure of the Hg(II) . NADPH complex was determined with 1H and 13C NMR spectroscopy and homonuclear decoupling and was shown to have Hg covalently attached to C-5 of the nicotinamide ring. From these results, we propose that Hg(II) reacts with the double bond between C-5 and C-6 to form a mercuronium ion which is opened by the nucleophilic attack of water on C-6. Two conformations of the Hg(II) . NADPH complex were detected, corresponding to the formation of the mercuronium ion on either the a or b side of the nicotinamide ring. Fluorescence quenching studies with the Hg(II) . NADPH complex and the flavoenzyme mercuric reductase showed that the complex could effectively bind (Kd = 2.3 microM), but could not reduce the enzyme.

Sexual behaviour of male rats injected with the anti-oestrogen MER-25 during infancy.

Newborn male rats were injected SC with 50, 100 or 200 micrograms MER-25 or 0.05 ml oil daily for the first 10 days of life. As adults, they were tested for male sexual behaviour both before and after castration and replacement with testosterone propionate, and for female sexual behaviour after injections of oestradiol benzoate followed by progesterone. Injections of 100 and 200 micrograms MER-25/day during infancy caused significantly fewer rats to ejaculate than 0.05 ml oil/day in both series of tests for male sexual behaviour. The reduced occurrence of ejaculation could not be related to defective penile development as there was no significant difference in penis weights or the numbers of penile spines between the MER-25 and oil-injected rats. All doses of MER-25 caused significantly more lordosis behaviour after oestrogen and progesterone than did injections of oil. These results provide further evidence that neonatal testicular androgens must be converted to oestrogen in the brain in order to organise male sexual behaviour patterns, including the neural substrate for ejaculation, as well as to suppress female sexual behaviour.