Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 22
Filter
1.
Thromb Haemost ; 112(2): 311-22, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24718367

ABSTRACT

High on-treatment platelet reactivity (HPR) has been identified as an independent risk factor for ischaemic events. The randomised, double-blind, TRIPLET trial included a pre-defined comparison of HPR in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) following a placebo/600-mg clopidogrel loading dose (LD) immediately before a subsequent prasugrel 60-mg or 30-mg LD. Platelet reactivity was assessed using the VerifyNow® P2Y12 assay (P2Y12 Reaction Units, PRU) within 24 hours (h) following the placebo/clopidogrel LD (immediately prior to prasugrel LD), and at 2, 6, 24, 72 h following prasugrel LDs. The impact of CYP2C19 predicted metaboliser phenotype (extensive metabolisers [EM] and reduced metabolisers [RM]) on HPR status was also assessed. HPR (PRU ≥240) following the clopidogrel LD (prior to the prasugrel LD) was 58.5% in the combined clopidogrel LD groups. No significant difference was noted when stratified by time between the clopidogrel and prasugrel LDs (≤6 hs vs>6 h). At 6 h following the 2nd loading dose in the combined prasugrel LD groups, HPR was 7.1%, with 0% HPR by 72 h. There was no significant effect of CYP2C19 genotype on pharmacodynamic (PD) response following either prasugrel LD treatments at any time point, regardless of whether it was preceded by a clopidogrel 600-mg LD. In conclusion, in this study, patients with ACS intended for PCI showed a high prevalence of HPR after clopidogrel 600-mg LD regardless of metaboliser status. When prasugrel LD was added, HPR decreased substantially by 6 h, and was not seen by 72 h.


Subject(s)
Acute Coronary Syndrome/therapy , Blood Platelets/drug effects , Drug Substitution , Percutaneous Coronary Intervention , Piperazines/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Thiophenes/administration & dosage , Ticlopidine/analogs & derivatives , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Aged , Blood Platelets/metabolism , Clopidogrel , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Double-Blind Method , Drug Administration Schedule , Drug Resistance , Female , Genotype , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Phenotype , Piperazines/adverse effects , Piperazines/metabolism , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/metabolism , Platelet Function Tests , Prasugrel Hydrochloride , Thiophenes/adverse effects , Thiophenes/metabolism , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Ticlopidine/metabolism , Time Factors , Treatment Outcome
2.
Int J Geriatr Psychiatry ; 16 Suppl 1: S33-61, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11748788

ABSTRACT

OBJECTIVE: Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available. METHOD: Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H(1) receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed. RESULTS AND CONCLUSION: In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic-like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders.


Subject(s)
Alzheimer Disease/drug therapy , Pirenzepine/analogs & derivatives , Pirenzepine/adverse effects , Adverse Drug Reaction Reporting Systems , Aged , Animals , Benzodiazepines , Brain/drug effects , Drug Evaluation, Preclinical , Humans , Neurologic Examination/drug effects , Olanzapine , Pirenzepine/therapeutic use , Receptors, Neurotransmitter/drug effects
3.
Circulation ; 104(8): 870-5, 2001 Aug 21.
Article in English | MEDLINE | ID: mdl-11514371

ABSTRACT

BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/administration & dosage , Coronary Disease/therapy , Immunoglobulin Fab Fragments/administration & dosage , Registries/statistics & numerical data , Thrombocytopenia/diagnosis , Vascular Patency/drug effects , Abciximab , Angioplasty, Balloon, Coronary/adverse effects , Antibodies/blood , Antibodies/pharmacology , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/immunology , Aspirin/administration & dosage , Coronary Disease/blood , Disease-Free Survival , Drug Administration Schedule , Hemorrhage/etiology , Heparin/administration & dosage , Humans , Immunoglobulin Fab Fragments/adverse effects , Immunoglobulin Fab Fragments/immunology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/immunology , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Postoperative Complications/prevention & control , Thrombocytopenia/etiology , Treatment Outcome , United States
4.
Ann Thorac Surg ; 70(2): 516-26, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10969673

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Blood Loss, Surgical , Coronary Artery Bypass , Immunoglobulin Fab Fragments/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Abciximab , Angioplasty, Balloon, Coronary , Emergency Treatment , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Risk Factors , Stents
5.
Am Heart J ; 140(3): 492-501, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10966553

ABSTRACT

BACKGROUND: We examined the ex vivo platelet aggregation profiles of patients who underwent percutaneous coronary intervention and received either abciximab, ticlopidine, or both agents. STUDY DESIGN AND METHODS: The trial was a prospective, nonrandomized, single-center, open-label study of 42 patients undergoing percutaneous coronary intervention who received the following regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 microg/kg per minute infusion); group 2, ticlopidine (250 mg twice daily for 14 consecutive days, initiated 12 to 18 hours before intervention); group 3, abciximab plus ticlopidine initiated 12 to 18 hours before procedure; and group 4, abciximab plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation measurements to adenosine diphosphate (ADP) and a thrombin receptor activating peptide (TRAP, 8 micromol/L) were obtained before ticlopidine treatment, after initiation of ticlopidine, and immediately before abciximab treatment and intervention, then at several time periods after onset of abciximab treatment. Platelet surface abciximab levels were monitored by flow cytometry. RESULTS: Neither ticlopidine regimen resulted in appreciable platelet inhibition before intervention and before administration of abciximab. In the ticlopidine-only arm, suppression of platelet aggregation to the weakest stimuli (5 micromol/L ADP; 23% +/- 7.5%) was detected within 24 hours after intervention, with maximal inhibition to both 5 and 20 micromol/L ADP observed 7 days after intervention (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine marginally suppressed TRAP-mediated platelet activation at times when maximal effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine regimen appreciably enhanced platelet inhibition during or shortly after cessation of abciximab treatment. For all 3 abciximab treatment arms, profound inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was observed 2 hours after treatment. In the abciximab-only arm, platelet aggregation responses gradually recovered, with the rate of response directly proportional to the strength of stimuli. However, in the ticlopidine plus abciximab arms, recovery of platelet aggregation at later times (7 and 14 days) reached a plateau and reflected the extent of inhibition observed in ticlopidine-treated patients. No difference in the clearance of surface-bound abciximab from circulating platelets was observed between the abciximab and abciximab plus ticlopidine arms. CONCLUSIONS: Concomitant abciximab plus ticlopidine treatment yields a platelet inhibition profile that is a composite of the effects of the 2 agents. In the early stages of treatment, inhibition of ex vivo platelet aggregation was mediated primarily by abciximab; effects were more moderate and were predominately mediated by ticlopidine.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Antibodies, Monoclonal/administration & dosage , Immunoglobulin Fab Fragments/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Ticlopidine/administration & dosage , Abciximab , Aged , Coronary Thrombosis/physiopathology , Coronary Thrombosis/prevention & control , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Platelet Function Tests , Postoperative Complications/prevention & control , Prospective Studies
6.
Drugs Aging ; 16(3): 179-87, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10803858

ABSTRACT

With increasing age of the general population, cardiovascular diseases are becoming a greater health burden. Coronary artery disease remains a major cause of morbidity and mortality worldwide. Among the various pathophysiological processes, platelets play a pre-eminent role. With the identification of the glycoprotein (GP) IIb/IIIa receptor as the final common pathway for platelet aggregation, potent antiplatelet agents have been developed. These GP IIb/IIIa antagonists have been shown to be effective in improving outcomes among patients undergoing percutaneous coronary interventions and for the treatment of acute coronary syndromes. By pooling the results of several large-scale trials, these benefits have been found to extend to the elderly population. Among 7860 patients undergoing percutaneous coronary intervention, the occurrence of death or myocardial infarction at 30 days was reduced from 10.0 to 5.9% (odds ratio 0.56; 95% confidence level, 0.37 to 0.83) with abciximab compared with placebo, in those >70 years of age. Importantly, this benefit was achieved without an increase in major bleeding complications. Similarly favourable trends were also observed among elderly patients treated with tirofiban or eptifibatide for acute coronary syndromes. As such, GP IIb/IIIa antagonists are effective in preventing ischaemic complications and can be safely administered to elderly patients.


Subject(s)
Aged/physiology , Cardiovascular Diseases/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Humans , Platelet Aggregation Inhibitors/adverse effects
7.
Circulation ; 101(10): 1122-9, 2000 Mar 14.
Article in English | MEDLINE | ID: mdl-10715258

ABSTRACT

BACKGROUND: Abciximab and ticlopidine reduce adverse cardiovascular events after percutaneous transluminal coronary angioplasty (PTCA). The goal of the current study was to determine if combined abciximab/ticlopidine therapy inhibits arterial thrombosis more effectively than either treatment alone. The effect of each therapy on platelet-leukocyte interactions was also investigated. METHODS AND RESULTS: Whole blood samples from 14 patients undergoing PTCA who received abciximab therapy, ticlopidine therapy, or both treatments were evaluated using dynamic experimental systems. Mural thrombus formation under arterial shear conditions (1500 s(-1)) was determined in a parallel plate flow chamber. Shear-induced platelet aggregation was evaluated using a cone-and-plate viscometer at a shear rate of 3000 s(-1). Of the 3 treatments, combined abciximab/ticlopidine therapy produced the most consistent reduction in shear-induced platelet aggregation and the most prolonged inhibition of mural thrombosis. Three days after PTCA, abciximab/ticlopidine treatment decreased mural thrombus formation to approximately 50% of baseline values. Abciximab treatment alone inhibited mural thrombosis for only 1 day after PTCA, whereas ticlopidine treatment alone had no significant effect. Two hours after PTCA, abciximab therapy significantly decreased the number of circulating platelet-neutrophil aggregates but significantly enhanced P-selectin-mediated leukocyte adhesion on the collagen/von Willebrand factor-platelet surface. CONCLUSIONS: Combined therapy with abciximab and ticlopidine has a prolonged inhibitory effect on mural thrombosis formation relative to either treatment alone. Further, we demonstrated an unexpected effect of abciximab in enhancing P-selectin-mediated leukocyte adhesion.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/therapeutic use , Anticoagulants/therapeutic use , Blood Platelets/drug effects , Immunoglobulin Fab Fragments/therapeutic use , Leukocytes/drug effects , Thrombosis/prevention & control , Ticlopidine/therapeutic use , Abciximab , Antibodies, Monoclonal/pharmacology , Anticoagulants/pharmacology , Blood Platelets/physiology , Drug Therapy, Combination , Humans , Immunoglobulin Fab Fragments/pharmacology , Leukocytes/physiology , Membrane Glycoproteins/physiology , P-Selectin/physiology , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Thrombosis/etiology , Ticlopidine/pharmacology
8.
Catheter Cardiovasc Interv ; 48(4): 430-4, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10559827

ABSTRACT

The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/therapeutic use , Anticoagulants/therapeutic use , Heparin/therapeutic use , Immunoglobulin Fab Fragments/therapeutic use , Myocardial Infarction/therapy , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Abciximab , Adult , Aged , Female , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Pilot Projects , Prospective Studies
10.
Am Heart J ; 138(1 Pt 2): S33-8, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10385789

ABSTRACT

Even with continued improvements in the technology of percutaneous coronary intervention (PCI), approximately 10% to 20% of patients undergoing PCI will require repeat procedures within 1 year. Furthermore, because of the chronic nature of coronary artery disease, many patients will require additional treatment with PCI well after an initial episode of care. Abciximab (ReoPro), a chimeric (murine/human) monoclonal antibody fragment (c7E3 Fab), has been shown to significantly improve periprocedural and long-term outcomes associated with PCI and to reduce the need for repeat target vessel revascularization. However, because the structure of abciximab is derived from an antibody, concern has been raised about subsequent repeat administration. To prospectively evaluate the safety and efficacy of abciximab readministration, we established the ReoPro Readministration Registry with the intent to determine the efficacy, human antichimeric antibody response and rates of thrombocytopenia, bleeding, intracranial hemorrhage, and anaphylaxis in at least 500 patients being retreated with abciximab. The study was conducted at 19 centers beginning in March 1997. This article details interim data that are based on the first 329 patients. Data to date indicate that readministration with abciximab is safe and efficacious and that the same indications for first-time use should apply to subsequent readministration.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Antibodies, Monoclonal/adverse effects , Coronary Disease/drug therapy , Immunoglobulin Fab Fragments/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Registries/statistics & numerical data , Abciximab , Antibodies/immunology , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Humans , Immunoglobulin Fab Fragments/administration & dosage , Immunoglobulin Fab Fragments/immunology , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/immunology , Prospective Studies , Recurrence , Thrombocytopenia/etiology
11.
Circulation ; 98(8): 734-41, 1998 Aug 25.
Article in English | MEDLINE | ID: mdl-9727542

ABSTRACT

BACKGROUND: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. METHODS AND RESULTS: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. CONCLUSIONS: Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.


Subject(s)
Angioplasty , Antibodies, Monoclonal/therapeutic use , Immunoglobulin Fab Fragments/therapeutic use , Myocardial Infarction/therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Abciximab , Aged , Antibodies, Monoclonal/adverse effects , Combined Modality Therapy , Double-Blind Method , Female , Humans , Immunoglobulin Fab Fragments/adverse effects , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Postoperative Hemorrhage/chemically induced , Stents , Treatment Outcome
12.
Circulation ; 94(9): 2083-9, 1996 Nov 01.
Article in English | MEDLINE | ID: mdl-8901655

ABSTRACT

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.


Subject(s)
Angina, Unstable/drug therapy , Myocardial Ischemia/chemically induced , Peptides/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Substance Withdrawal Syndrome , Adult , Aged , Aged, 80 and over , Angina, Unstable/complications , Anticoagulants/pharmacology , Aspirin/pharmacology , Bleeding Time , Dose-Response Relationship, Drug , Double-Blind Method , Electrocardiography, Ambulatory , Eptifibatide , Female , Hemorrhage/chemically induced , Heparin/pharmacology , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Ischemia/complications , Myocardial Ischemia/drug therapy , Peptides/adverse effects , Placebos , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Sex Factors
13.
J Am Coll Cardiol ; 23(5): 1216-23, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8144792

ABSTRACT

OBJECTIVES: We studied canine coronary arterial vasoreactivity after occlusion and reperfusion to examine whether reduced flow or pressure contributed to the abnormalities observed. BACKGROUND: Ischemia and reperfusion alter endothelial and myocardial function. Causative factors may include altered flow, complement activation or free radical production by endothelial or white blood cells after reoxygenation and neutrophil activation. METHODS: The coronary arteries of anesthetized, open chest dogs were subjected to 90-min occlusion +/- 2 h of reperfusion. The effect of reperfusion on arterial responses to intracoronary acetylcholine, nitroprusside and phenylephrine was studied using in vivo ultrasound. Arterial segments were also harvested, perfused ex vivo with cell-free buffer and exposed to potassium chloride, nitroprusside, acetylcholine and bradykinin. The effect of ex vivo flow cessation with or without maintained intralumen pressure was also studied. RESULTS: Results are expressed as mean value +/- SEM. In vivo arterial cross-sectional area increased during infusion with acetylcholine (10(-5) mol/liter [18.5 +/- 9%]) and nitroprusside (10(-5) mol/liter [22.5 +/- 10%]) and decreased with phenylephrine (10(-5) mol/liter [7.6 +/- 7%]). After reperfusion, acetylcholine caused 13.5 +/- 9% vasoconstriction. Nitroprusside and phenylephrine responses were unchanged. Reperfused arterial segments also showed impaired vasodilation in response to 10(-6) mol/liter of acetylcholine (10.6 +/- 5.1% vs. 47.1 +/- 4.9% in control vessels) and 10(-8) mol/liter of bradykinin (4.4 +/- 6.7% vs. 27.9 +/- 8% in control vessels). Ex vivo flow cessation impaired acetylcholine-mediated vasodilation, but this abnormality was prevented when high intralumen pressure was maintained during the no-flow period. CONCLUSIONS: Reduction in flow and intralumen pressure contribute to the impaired acetylcholine-mediated vasodilation seen after coronary occlusion. This is prevented by maintaining high intralumen pressure during the no-flow period, suggesting that hemodynamic forces may change endothelial function independent of circulating complement or blood cell elements.


Subject(s)
Coronary Vessels/physiology , Endothelium, Vascular/physiology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion , Vasodilation , Acetylcholine/pharmacology , Animals , Coronary Vessels/diagnostic imaging , Coronary Vessels/drug effects , Dogs , Female , Hemodynamics , Male , Nitroprusside/pharmacology , Pericardium/physiology , Phenylephrine/pharmacology , Ultrasonography
15.
Md Med J ; 40(6): 485-91, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1830634

ABSTRACT

The efficacy of intravenous thrombolytic agents in preserving left ventricular function and in decreasing mortality from an acute myocardial infarction was demonstrated in the 1980s. The 1990s will concentrate on adjunctive therapy to thrombolysis in the treatment of an acute myocardial infarction.


Subject(s)
Myocardial Infarction/drug therapy , Thrombolytic Therapy/standards , Clinical Trials as Topic , Cost-Benefit Analysis , Humans , Meta-Analysis as Topic , Myocardial Infarction/mortality , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/economics
16.
JAMA ; 263(20): 2766-71, 1990.
Article in English | MEDLINE | ID: mdl-2332919

ABSTRACT

We studied exercise training combined with the use of antihypertensive drugs and examined the following questions. (1) Are there additive antihypertensive benefits with exercise and drug therapy combined? (2) Does drug therapy limit exercise-induced lipid improvements? (3) Does exercise that includes weight training and walking/jogging affect the left ventricle? Fifty-two hypertensive men were randomly assigned, double-blind, to diltiazem hydrochloride, sustained release (360 mg daily), propranolol hydrochloride (240 mg daily), or placebo and exercised three times per week for 10 weeks. Baseline blood pressure (145/97 mm Hg) fell after training (131/84 mm Hg) in all groups. Exercise decreased total and low-density lipoprotein cholesterol levels in all groups. Increases in the levels of high-density lipoprotein cholesterol were similar in placebo and diltiazem groups, whereas the propranolol group changed in an opposite direction. In all groups, left ventricular mass increased with training, while diastolic function was unchanged. We conclude that (1) drug therapy provided no additive benefit to the antihypertensive effects of exercise, (2) propranolol limited improvements in high-density lipoprotein cholesterol, and (3) exercise did not adversely affect the left ventricle.


Subject(s)
Antihypertensive Agents/therapeutic use , Exercise , Hypertension/therapy , Adolescent , Adult , Analysis of Variance , Blood Pressure , Blood Pressure Determination , Diltiazem/therapeutic use , Echocardiography , Hemodynamics , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Lipoproteins/blood , Male , Middle Aged , Patient Compliance , Propranolol/therapeutic use , Ventricular Function
17.
Med Sci Sports Exerc ; 22(2): 171-7, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2355813

ABSTRACT

This was a prospective, randomized, double-blind, placebo-controlled trial to establish whether beta blockers or calcium-channel blockers limit exercise capacity and training responses in men with mild hypertension. Circuit weight and aerobic training was used to assess the effects of drugs on cardiovascular fitness and muscle strength. Fifty-two sedentary men, ages 25-59 yr, with a diastolic blood pressure of 90-105 mm Hg off drugs, without significant ST depression during maximal stress testing, received diltiazem, propranolol, or placebo. Maximal oxygen uptake (VO2max) and exercise duration during treadmill testing, as well as one-repetition maximal strength, were assessed on eight weight machines after a single-blind placebo baseline, after 2 wk of drug run-in, and after 10 wk of exercise training. Total daily doses were 240 mg for propranolol and 360 mg for diltiazem. Propranolol decreased VO2max after drug run-in (P less than 0.05). Exercise training increased VO2max (P less than 0.05) in the diltiazem and placebo groups. After training VO2max in the propranolol group increased (P less than 0.05) from run-in but not beyond baseline levels. Thus, the reduction of VO2max consequent to propranolol therapy limited the overall benefits of training. Exercise duration did not change with run-in and increased (P less than 0.05) with training by 22%, 19%, and 10% for the diltiazem, placebo, and propranolol groups, respectively. Strength after run-in was unchanged, and exercise training increased strength (P less than 0.0001) on all weight machines in all groups. The results show an advantage of diltiazem to propranolol, particularly among physically active patients engaged in aerobic exercise who require antihypertensive therapy.


Subject(s)
Diltiazem/pharmacology , Exercise/physiology , Hypertension/drug therapy , Propranolol/pharmacology , Adolescent , Adult , Blood Pressure/drug effects , Diltiazem/therapeutic use , Exercise Test , Heart Rate/drug effects , Humans , Male , Middle Aged , Oxygen/metabolism , Propranolol/therapeutic use , Pulmonary Gas Exchange/drug effects , Weight Lifting
18.
Med Sci Sports Exerc ; 21(6): 694-7, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2696857

ABSTRACT

Although several studies have evaluated the effects of endurance training on left ventricular (LV) function, few studies have looked at resistive training effects. Acute isometric exercise increases blood pressure and has little effect on LV function, causing only mild increases in ejection fraction and stroke volume index. However, acute isometric exercise does increase LV diastolic diameter to a lesser extent than dynamic exercise. Most studies of resistive training on LV function have been cross-sectional or short term (10 to 12 wk) training studies on athletes and suggest that increases in LV wall thickness and mass are dependent upon the intensity and duration of training. Most resistive training studies show no increase in left ventricular volume, as can be seen in endurance trained athletes. Despite the increase in LV mass with resistive training, indices of LV systolic and diastolic function do not change. In hypertensive and cardiac patients with normal LV function at rest, resistive training increases LV mass index without deleterious effects on LV systolic and diastolic function. However, in patients with abnormal resting LV function, resistive training can have adverse effects on LV systolic function. Overall, moderate levels of resistive training can be a useful adjunct to cardiac rehabilitation programs, with the caveat that it be used with caution in patients with abnormal LV function at rest.


Subject(s)
Heart/physiology , Physical Education and Training , Weight Lifting , Coronary Disease/prevention & control , Coronary Disease/rehabilitation , Echocardiography , Exercise , Heart/physiopathology , Heart Ventricles , Humans
19.
Am J Cardiol ; 62(17): 1202-7, 1988 Dec 01.
Article in English | MEDLINE | ID: mdl-3195481

ABSTRACT

Although conversion of atrial fibrillation (AF) to sinus rhythm can usually be accomplished by electrical or drug therapy, effective atrial systole may not be restored. To investigate the return of atrial transport function and its relation to the duration of the arrhythmia, Doppler echocardiography was performed after conversion in 18 patients with acute AF (less than or equal to 1 week duration), 14 patients with chronic AF (greater than 1 week duration) and 15 control patients. Flow velocities during rapid filling (E wave) and atrial systole (A wave) were measured in both left and right ventricles. Patients in the acute AF group had left ventricular A waves (49 +/- 4 cm/s) and A/E ratios (0.97 +/- 0.1) similar to those of the control patients (55 +/- 7 cm/s, 0.87 +/- 0.08, respectively). In contrast, patients in the chronic AF group had much smaller A waves (19 +/- 5 cm/s) and A/E ratios (0.30 +/- 0.08) than those in the other 2 groups (p less than 0.001). Five patients with chronic AF (36%) had complete left atrial paralysis (A/E = 0) despite normal sinus P waves. Measurements in the right ventricle showed similar differences among the groups. Patients with chronic AF who maintained sinus rhythm showed an increase in A/E ratio to control levels, from 0.45 +/- 0.1 to 0.93 +/- 0.1 (p = 0.003) at 48 days (average) after conversion. Thus, atrial transport function is normal after brief periods of AF, but reduced or absent when conversion is achieved after the arrhythmia has been sustained greater than 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Atrial Fibrillation/therapy , Myocardial Contraction , Acute Disease , Aged , Atrial Fibrillation/drug therapy , Blood Flow Velocity , Cardiac Output , Chronic Disease , Echocardiography , Electric Countershock , Follow-Up Studies , Heart Atria/physiopathology , Heart Rate , Humans , Middle Aged , Prospective Studies
20.
Circ Res ; 60(2): 238-45, 1987 Feb.
Article in English | MEDLINE | ID: mdl-2952364

ABSTRACT

To determine whether the relative decline in cardiac myosin isoenzyme V1 with maturation continues progressively into senescence and whether thyroxine could reverse age-associated changes in the myosin isoenzyme profile and contraction, rats 2, 8, and 24 months old were treated with thyroxine, 6.4 mg/kg, for 7 days. Myosin isoenzymes, Ca2+-myosin ATPase activities, and isometric contractile function were measured in cardiac preparations from thyroxine-treated animals and age-matched controls. Right ventricular hypertrophy did not occur with aging in controls. Thyroxine increased right ventricular weight in each age group compared to the control group. Body weight decreased by 10% in all thyroxine-treated rats. The relative right ventricular V1 isoenzyme content progressively decreased from 75 +/- 1% to 54 +/- 1% and 14 +/- 1% in controls at 2, 8, and 24 months, respectively, and was associated with a reciprocal increase in V3 myosin isoenzyme. Ca2+-myosin ATPase activity also progressively declined monotonically with age in the control rats from 854 +/- 28 nmol Pi/mg prot/min at 2 months to 529 +/- 28 nmol Pi/mg prot/min at 24 months. Thyroxine administration increased right ventricular V1 at each age to 97 +/- 2%, 73 +/- 2%, and 59 +/- 2% at 2, 8, and 24 months, respectively. A thyroxine induced increase in the Ca2+-myosin ATPase activity could be detected only in the 24-month-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adenosine Triphosphatases/metabolism , Aging/metabolism , Isoenzymes/metabolism , Myocardial Contraction/drug effects , Myocardium/enzymology , Myosins/metabolism , Thyroxine/pharmacology , Aging/drug effects , Animals , Hyperthyroidism/enzymology , Male , Rats , Rats, Inbred Strains , Thyroxine/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...