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.

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.

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.

Sexual behaviour of neonatally castrated rats injected during infancy with oestrogen and dihydrotestosterone.

Male rats were castrated on the day of birth (day 1) and injected with either testosterone, dihydrotestosterone, a synthetic oestrogen (RU 2858 + dihydrotestosterone, or oil from days 1 to 5. The aromatizable androgen, testosterone, and RU 2858 suppressed both cyclic gonadotrophin secretion, indicated by the absence of corpora lutea from implanted ovarian grafts, and the behavioural response to oestradiol benzoate + progesterone injections in adulthood. The 5alpha-reduced androgen, dihydrotestosterone alone did not affect gonadotrophin secretion or female receptive behaviour, but like testosterone, it increased penis development in response to testosterone propionate, and this was positively correlated with copulatory efficiency, i.e. the ratio of intromission to mount frequencies. Nevertheless, ejaculation only occurred among animals that had received testosterone or RU 2858 + dihydrotestosterone. The results support the concept that during the preinatal period, neural conversion of androgens to oestrogens is important both for the suppression of female gonadotrophin secretion and behaviour patterns as well as for the organization of male behaviour patterns. The 5alpha-reduction of unsaturated C19-steriods to dihydrotestosterone in peripheral tissues is also required to complete the development of the male genital tract.

PIP: Experiments were carried out to compare the masculine sexual behavior of male rats castrated on the day of birth (Day 1) and injected with testosterone (an aromatizable androgen), dihydrotestosterone (a nonaromatizable androgen), or an estrogen. Litters of Sprague-Dawlet rats were castrated under cryoanesthesia on Day 1 and assigned to 1 of 5 treatment groups: Group 1 received 50 mcg testosterone, Group 2 received 50 mcg dihydrotestosterone, Group 3 received RU 2858, Group 4 received 50 mcg dihydrotestosterone plus 1 mcg RU 2858, and Group 5 was given .05 ml oil. During Week 5 an ovary from a prepubertal female rat was transplanted under the left kidney capsule of each rat. Each rat was given 20 mcg estradiol benzoate per kg followed by .5 mg progesterone. Sexual receptivity was assessed. The aromatizable androgen, testosterone, and RU 2858 suppressed both cyclic gonadotropin secretion and the behavioral response to estradiol benzoate plus progesterone injections. Gonadotropin secretion or female receptive behavior was unaffected by dihydrotestosterone, but it increased penis development in response to testosterone propionate which was positively correlated with copulatory efficiency. Ejaculation only occurred in those animals that had recived testosterone or RU 2858 plus dihydrotestosteorne. During the perinatal period natural conversion of androgens to estrogens is needed for the suppression of gonadotropin secretion and behavior and for the development of male behavior patterns.

Effects of oestradiol-17beta, oestradiol benzoate and the synthetic oestrogen RU 2858 on sexual differentiation in the neonatal female rat.

Groups of neonatal female rats were treated for the first 5 days of life with oestradiol-17beta, oestradiol benzoate or a synthetic oestrogen, 11beta-methoxy-17-ethynyl-1,3,5(10)-oestratriene-3,17beta-diol (RU 2858), in daily doses ranging from 0-5 to 1000 ng. Oestradiol-17beta had no effect on adult ovarian cyclicity or sexual receptivity after ovariectomy and oestrogen+ progesterone treatment. Ovarian cyclicity was prevented by 100 ng or more oestradiol benzoate/day, and by all doses of RU 2858. Only rats receiving 50 ng oestradiol benzoate/day or 0-5 ng RU 2858/day showed normal receptivity. The defeminizing action of RU 2858 was at least 100 times greater than that of oestradiol benzoate; it is suggested that this greater potency is due to the low affinity of RU 2858 for the oestradiol-binding protein in the plasma of neonatal rats. These results indicate that defeminization of the neonatal rat brain can be induced by physiological amounts of oestrogen, and are discussed with reference to the action of testosterone.

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.

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.

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.