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Biomedical subjects

Peter Berger

Publications and source records attributed to Peter Berger.

At least 19 recordsLinked to original sources
PubMed2007

Thrombus predicts ischemic complications during percutaneous coronary intervention in saphenous vein grafts: results from TARGET (do Tirofiban and ReoPro give similar efficacy trial?).

BACKGROUND: Saphenous vein graft (SVG) percutaneous coronary intervention (PCI) carries a high risk of ischemic complications. However, there are scant recent data to identify which SVG lesions carry particularly high risk in recent years. We studied demographic and angiographic factors associated with ischemic complications after SVG PCI without distal protection in the TARGET (do tirofiban and reopro give similar efficacy trial?) study. METHODS: TARGET was a multicenter double-dummy, double-blinded study randomizing 4,809 PCI patients to tirofiban or abciximab. Of these, 254 patients underwent PCI involving an SVG lesion. The primary endpoint of this analysis was major adverse cardiac events (MACEs) at 30 days, including death, nonfatal myocardial infarction (MI), and urgent target vessel revascularization. RESULTS: No demographic characteristic was associated with 30-day MACE. Lesion length > 20 mm (odds ratio [OR] = 2.7, P = 0.03), thrombus (OR = 3.9, P = 0.003), eccentricity (P = 0.001), thrombolysis in myocardial infarction flow < 3 post-procedure (OR = 5.6, P = 0.037), and >1 target lesion (OR = 2.5, P = 0.035) were univariate variables associated with 30-day MACE. Multivariate analysis associated only thrombus (OR = 3.8, P = 0.015) with 30-day MACE. No difference in outcomes was noted between patients receiving abciximab and tirofiban. SVG patients had lesser angiographic success (95.6% vs. 98%, P = 0.04) and increased 30-day Q-wave MI (2.5% vs. 0.9%, P = 0.039) compared with non-SVG patients, but a similar incidence of death (0% vs. 0.4%), non-Q-MI (5.9% vs. 4.5%), and target vessel revascularization (0.5% vs. 1%). CONCLUSION: In the era of routine stenting and GpIIb/IIIa inhibitors, thrombus is the angiographic characteristic most closely associated with adverse outcomes of SVG PCI.

Abciximab↗
PubMed2006

Association between plasma adiponectin levels and unstable coronary syndromes.

AIMS: Obesity is a risk factor for an acute coronary syndrome (ACS). The association between elevated body mass index (BMI) and ACS is independent of most traditional risk factors, suggesting a possible contribution of other body fat-related mediators. This study evaluated the association between adiponectin and ACS. METHODS AND RESULTS: Four hundred and ninety-nine patients undergoing coronary angiography were divided into a subgroup without (n = 331) and with ACS (n = 168). In multiple regression analysis, higher adiponectin levels were independently associated with a lower risk of ACS [odds ratio (OR) = 0.61; 95% CIs: 0.46-0.81; P < 0.001]. In contrast, a higher BMI, a history of myocardial infarction, C-reactive protein, and angiographic coronary artery disease severity were all associated with a higher risk. The greatest increase in risk for ACS was seen at adiponectin levels < or = 5.5 microg/mL. CONCLUSION: Higher plasma adiponectin levels are independently associated with a lower risk of ACS.

Acute Coronary Syndrome↗
PubMed2006

Glycosylation patterns of human chorionic gonadotropin revealed by liquid chromatography-mass spectrometry and bioinformatics.

Due to their extensive structural heterogeneity, the elucidation of glycosylation patterns in glycoproteins such as the subunits of human chorionic gonadotropin (hCG), hCG-alpha, and hCG-beta, remains one of the most challenging problems in the proteomic analysis of post-translational modifications. In consequence, glycosylation is usually studied after decomposition of the intact proteins to the proteolytic peptide level. However, by this approach all information about the combination of the different glycopeptides in the intact protein is lost. In this study we have, therefore, attempted to combine the results of glycan identification after tryptic digestion with molecular mass measurements on the native starting material of the new first WHO Reference Reagents (RR) for hCG-alpha (99/720) and hCG-beta (99/650). Despite the extremely high number of possible combinations of the glycans identified in the tryptic peptides by HPLC-MS (>1000 for hCG-alpha and >10 000 for hCG-beta), the mass spectra of intact hCG-alpha and hCG-beta revealed only a limited number of glycoforms present in hCG preparations from pools of pregnancy urines. Peak annotations for hCG-alpha were performed with the help of a bioinformatic algorithm that generated a database containing all possible modifications of the proteins, including modifications possibly introduced during sample preparation such as oxidation or truncation, for subsequent searches for combinations fitting the mass difference between the polypeptide backbone and the measured molecular masses. Fourteen different glycoforms of hCG-alpha, containing biantennary, partly sialylized hybrid-type glycans, including methionine-oxidized and N-terminally truncated forms, were identified. Mass spectra of high quality were also obtained for hCG-beta, however, a database search mass accuracy of +/-5 Da was insufficient to unambiguously assign the possible combinations of post-translational modifications. In summary, mass spectrometric fingerprints of intact molecules were shown to be highly useful for the characterization of glycosylation patterns of different hCG preparations such as the new first WHO RR for immunoassays and could be the first step in establishing biophysical reference methods for hCG and related molecules.

Chorionic Gonadotropin↗
PubMed2006

Impact of treatment delays on outcomes of primary percutaneous coronary intervention for acute myocardial infarction: analysis from the CADILLAC trial.

BACKGROUND: The impact of treatment delays on outcomes after primary percutaneous coronary intervention for acute myocardial infarction is controversial. METHODS: The CADILLAC trial randomized 2082 patients with acute myocardial infarction to stenting versus percutaneous transluminal coronary angioplasty, each with or without abciximab. RESULTS: Earlier reperfusion (<3 vs 3-6 vs >6 hours) was associated with lower 1-year mortality (2.6% vs 4.3% vs 4.8%, P = .046 for <3 vs > or = 3 hours), more frequent grade 2 to 3 myocardial blush (55% vs 53% vs 44%, P = .003), more frequent complete ST-segment resolution (64% vs 68% vs 47%, P = .006), and greater improvement in left ventricular function. Early reperfusion (<3 vs 3-6 vs > or = 3 hours) was associated with lower mortality in high-risk patients (3.8% vs 6.9% vs 7.0%, P = .051 for <3 vs > or = 3 hours) but not in low-risk patients (1.4% vs 0.6% vs 1.0%, P = .63). Door-to-balloon times were independently correlated with mortality in patients presenting early after the onset of symptoms (< or = 2 hours, hazard ratio 1.24, P = .013) but not late (>2 hours, heart rate 0.88, P = .33). CONCLUSIONS: Early reperfusion results in superior clinical outcomes, enhanced microvascular reperfusion, and better recovery of left ventricular function. Incremental treatment delays impact mortality more in high-risk versus low-risk patients and more in patients presenting early versus late after the onset of symptoms. These data emphasize the importance of minimizing treatment delays and have implications regarding patient triage for primary percutaneous coronary intervention.

Aged↗
PubMed2006

[Schizophrenia and psychosis on the internet].

OBJECTIVE: The internet is an increasingly important source of information for patients concerning their illness. This has to be borne in mind concerning its growing influence on communications between patients and clinicians. The aim of this study is to assess the quality of German-language information on schizophrenia on the internet. METHOD: Two searches of the terms schizophrenia and psychosis were conducted, using the Google search engine set to produce only German hits. The quality of the first hundred resulting sites was assessed according to a range of criteria, including diagnosis and therapy, links and interactive offers. RESULTS: Evidence-based medical information was provided by more than half of the sites resulting from the search term schizophrenia and by less than one third of psychosis hits. Information and discussion on the relationship between drugs and psychosis appeared almost exclusively under the term psychosis. CONCLUSIONS: It is suggested that mental health care professionals can use knowledge on what sort of information their patients are confronted with on the internet in order to assist them in profiting from this source of information.

Germany↗
PubMed2005

Interferon-gamma induces neuroendocrine-like differentiation of human prostate basal-epithelial cells.

BACKGROUND: Prostatic neuroendocrine (NE) cells are intraglandular hybrid epithelial-neural-endocrine cells that express and secrete numerous hormones and neuropeptides, which presumably regulate growth, differentiation, and secretory activity of the prostatic epithelium. This specialized cell type appears to differentiate from a common basal/precursor/stem cell that also gives rise to the secretory epithelium. In order to elucidate mechanisms of NE-differentiation the effects of type 1 (alpha, beta) and type 2 (gamma) interferons (IFNs) on human prostate basal cells (PrECs) were evaluated. METHODS AND RESULTS: Application of alpha/beta IFN increased the expression of the cell-cycle inhibitor p21(CIP1) and inhibited DNA synthesis, while only IFN-gamma led to increased apoptosis, cell-cycle inhibitor p27(KIP1) upregulation, and differentiation of PrECs into NE-like cells. In vitro differentiated NE-like cells expressed the glycolytic enzyme neuron-specific enolase (NSE) and chromogranin A (CgA), known markers of NE-cells in vivo in the prostate. These NE-like cells also changed cytokeratin (CK) expression patterns by upregulating CK 8/18, predominantly found in terminally-differentiated secretory luminal/NE epithelial cells. CONCLUSIONS: IFN-gamma produced locally in the prostate by basal cells and, under proinflammatory conditions, by infiltrating lymphocytes could support NE cell differentiation and play a role in NE differentiation processes of tumor cells in hormone-refractory prostate cancer.

Antineoplastic Agents↗
PubMed2005

Insufficient protection for healthy elderly adults by tetanus and TBE vaccines.

Little information is available on post-vaccination antibody concentrations and the duration of protection in persons of more than 20 years of age. We, therefore, measured antibodies specific for tetanus (TT) or tick-borne encephalitis (TBE) virus in 734 adults (age 18-93 years, 382 females and 352 males) and evaluated these data in connection with the time point of the last vaccination against tetanus or TBE and age. This analysis revealed that the time of the last vaccination as well as age had highly significant effects on tetanus and TBE titers (p < 0.001). Our results show a strong decline in post-vaccination antibody concentrations with age, which sets in at the age of 40 in the case of tetanus, and is observed right throughout adult life in the case of TBE. Persons over 60 years of age frequently do not have protective antibody concentrations. We conclude that immunological responsiveness to vaccination decreases throughout adult life, and that conventional vaccination strategies designed for children and young adults cannot be uncritically applied in the elderly.

Adolescent↗
PubMed2005

The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution fixes the conformation of the C-terminal peptide.

Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross-reactivity while refocusing the immune response to the hCG(beta)-specific C-terminal peptide (CTP). To investigate the molecular basis for this change in epitope usage, we immunized mice with a plasmid encoding a truncated hCG(beta)-R68E chain lacking the CTP. The animals produced LH-cross-reactive antibodies, suggesting that the refocused immunogenicity of R68E is a consequence of epitope masking by a novel disposition of the CTP in the mutant rather than a structural change in the cross-reactive epitope region. This explanation was strongly supported by surface plasmon resonance analysis using a panel of anti-hCG(beta)-specific and anti-hCG(beta)/LH cross-reactive monoclonal antibodies (mAbs). Whereas the binding of the LH cross-reactive mAbs to hCG(beta)-R68E was eliminated, mAbs reacting with hCG(beta)-specific epitopes bound to hCG(beta) and hCG(beta)-R68E with identical affinities. In a separate series of experiments, we observed that LH cross-reactive epitopes were silent after immunization with a plasmid encoding a membrane form of hCG(beta)-R68E, as previously observed with the soluble mutant protein itself. In contrast, the plasmid encoding the soluble secreted form of hCG(beta)-R68E evoked LH cross-reactive antibodies, albeit of relatively low titer, suggesting that the handling and processing of the proteins produced by the two constructs differed.

Amino Acid Substitution↗
PubMed2005

Benign prostatic hyperplasia: age-related tissue-remodeling.

Aging and androgens are the two established risk factors for the development of benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE), which can lead to lower urinary tract symptoms (LUTS) in elderly men. BPH, consisting of a nodular overgrowth of the epithelium and fibromuscular tissue within transition zone and periurethral areas, is first detectable around the fourth decade of life and affects nearly all men by the ninth decade. The pathogenesis of BPH is still largely unresolved, but multiple partially overlapping and complementary theories have been proposed, all of which seem to be operative at least to some extent. In addition to nerve-, endocrine- and immune system, local para- and luminocrine pleiotrope mechanisms/factors are implicated in the prostatic tissue-remodeling process. Prostate tissue-remodeling in the transition zone is characterized by: (i) hypertrophic basal cells, (ii) altered secretions of luminal cells leading to calcification, clogged ducts and inflammation, (iii) lymphocytic infiltration with production of proinflammatory cytokines, (iv) increased radical oxygen species (ROS) production that damages epithelial and stromal cells, (v) increased basic fibroblast (bFGF) and transforming growth factor beta (TGF-beta 1) production leading to stromal proliferation, transdifferentiation and extracellular matrix production, (vi) altered autonomous innervation that decreases relaxation and leads to a high adrenergic tonus, (vii) and altered neuroendocine cell function and release of neuroendocrine peptides (NEP). This review summarizes the multifactorial nature of prostate tissue remodeling in elderly men with symptomatic BPH with a particular focus on changes of cell-cell interactions and cell functions in the human aging prostate.

Adult↗
PubMed2005

Effect of bare metal stenting on angiographic and clinical outcomes in diabetic and nondiabetic patients undergoing percutaneous coronary intervention of nonacute occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA).

The outcome after PTCA and coronary stenting of nonacute total coronary occlusions in the diabetic population is unknown. The main objective of the present report was to compare the angiographic and 1-year clinical outcomes in the diabetic and nondiabetic patients who were enrolled in the Total Occlusion Study of Canada (TOSCA), a prospective randomized controlled multicenter trial of primary stenting versus PTCA alone in nonacute native coronary artery occlusions. Of the 410 patients enrolled, 68 (16.5%) were diabetics. At 6-month follow-up, stenting resulted in significant improvement in angiographic outcome compared to PTCA alone in both diabetic and nondiabetic populations. Angiographic restenosis was significantly reduced by stenting in the nondiabetic population (69.3% vs. 55.2%; P = 0.009). A reduction in restenosis of a similar magnitude was observed with stenting in the diabetic population (71.1% vs. 59.3%; P = NS). At 1-year clinical follow-up, composite adverse cardiac event rates were similar for both strategies regardless of diabetic status. Target vessel revascularization was reduced by stenting compared to PTCA in diabetics (20% vs. 31.6%) and nondiabetics (21.5% vs. 30%). A significant reduction for any vessel revascularization following stenting compared to PTCA was observed in the nondiabetic population (28.5% vs. 38.8%; P = 0.05) but not in the diabetic subgroup (36.7% vs. 42%; P = NS). In conclusion, stenting appeared to be superior to PTCA alone, resulting in similar magnitude of reduction in angiographic restenosis and target vessel revascularization rates in diabetics and nondiabetics. Restenosis rates in all groups remain high. This analysis forms an important background for future studies that are needed to examine the effect of stenting with drug-eluting stents in diabetics as well as nondiabetics with nonacute coronary occlusions.

Angioplasty, Balloon↗
PubMed2005

Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation.

The development of age-related proliferative disorders of the prostate gland is supported by transdifferentiation and cellular senescence processes in the stroma. Both processes are involved in remodeling of stromal tissue, as observed in benign prostatic hyperplasia (BPH), and in "reactive stroma" adjacent to prostate cancer (PCa). It has been assumed that TGF-beta1 plays a key role in the aging prostate by inducing premature senescence and favoring myofibroblast differentiation. Therefore, we evaluated the stromal cell phenotypes of human primary adult prostatic fibroblasts (n=3) and the molecular and cellular mechanisms of growth arrest after treatment with TGF-beta1 and of in vitro cellular senescence. Microarray analysis, quantitative PCR, immunofluorescence and western blot revealed that cellular senescence and transdifferentiation of fibroblasts have distinct underlying mechanisms, pathways and gene and protein expression profiles in human PrSCs. In clear contrast to senescent cells, TGF-beta1-treated cells morphologically transdifferentiated into myofibroblasts with dense cytoskeletal fibers and increased expression of smooth muscle cell alpha-actin, calponin and tenascin. TGF-beta1 induced neither expression of senescence-associated markers nor genes involved in terminal growth arrest, such as senescence-associated beta-galactosidase and cyclin-dependent kinase (cdk) inhibitors p16(Ink4A) and p21(Cip1) but increased p15(Ink4B) protein expression. Differentiation inhibitor (Id-1) protein level down-regulation was observed under both conditions. Genes specifically up-regulated by transdifferentiation but not by cellular senescence of PrSCs were metalloproteinase 1 tissue inhibitor (Timp1), transgelin (Tagln), gamma 2 actin (Actg2), plasminogen activator inhibitor 1 (Serpinel), insulin-like growth factor binding protein 3 (Igfbp3), parathyroid hormone-like hormone (Pthlp), Tgfb-1, four and a half LIM domains 2 (Fhl-2), hydrogen peroxide-inducible clone 5 (Hic5) and cartilage oligomeric matrix protein (Comp). Other genes, such as Cdc28 protein kinase 1 (Cks1b), v-myb myeloblastosis viral oncogene homolog (MybL2), pyruvate kinase, muscle 2 (Pkm2) and Forkhead box M1 (FoxM1), were down-regulated only upon TGF-beta1 treatment but not by cellular senescence. Pyruvate dehydrogenase kinase 3 (Pdk3) and connective tissue growth factor (Ctgf) were up-regulated and hyaluronan synthase 3 (Has3) down-regulated under both conditions. Moreover, GageC1, a prostate/testis-specific protein overexpressed in symptomatic BPH and PCa was induced in transdifferentiated stromal cells. Genes such as GageC1 could be promising targets for therapeutic inhibitors of stromal tissue remodeling and progression of BPH and PCa.

Cell Differentiation↗
PubMed2005

Prolactins are natural inhibitors of angiogenesis in the retina.

PURPOSE: Disruption of the normally antiangiogenic environment of the retina leads to aberrant angiogenesis, the major cause of vision loss throughout the world. Prolactin (PRL), the hormone originally associated with milk production, can be proteolytically processed to 16K-PRL, a 16 kDa N-terminal PRL fragment with potent antiangiogenic and vasoconstrictive actions. This study was conducted to determine whether 16K-PRL is found naturally in the retina and plays a role in angiogenesis and vasodilation. METHODS: Expression of PRL mRNA in rat retina was determined by RT-PCR and in situ hybridization. Western blot was used to examine the expression of PRL and derived fragments in retinal homogenates. The role of PRL and 16K-PRL in the retina was studied by intravitreal injection of either antibodies against PRL or small interfering RNAs (siRNA), to suppress expression of retinal PRL mRNA. RESULTS: Rat retina expressed PRL mRNA in the outer nuclear, outer plexiform, inner nuclear, and ganglion cell layers. Both full-length PRL and N-terminal 16K-PRL were detected in retinal homogenates by polyclonal and monoclonal antibodies. The intravitreal injection of antibodies able to neutralize the actions of 16K-PRL increased the number of retinal blood vessels and capillary area by threefold. Furthermore, siRNA-mediated inhibition of PRL mRNA increased retinal neovascularization threefold and resulted in a significant increase in vasodilation. CONCLUSIONS: These results demonstrate that PRL is synthesized and cleaved to antiangiogenic 16K-PRL by retinal tissue and that these molecules play a key role in preventing angiogenesis in the healthy retina.

Angiogenesis Inhibitors↗
PubMed2004

Plasma leptin and prognosis in patients with established coronary atherosclerosis.

OBJECTIVES: This study was designed to evaluate the relationship between plasma leptin and prognosis in patients with angiographically confirmed coronary atherosclerosis. BACKGROUND: Experimental studies suggest that leptin, an adipose tissue-derived hormone, exerts important cardiovascular effects. METHODS: Study subjects were recruited prospectively from a cohort of patients undergoing clinically indicated coronary angiography (n = 382). The median duration of follow-up was four years. Follow-up information was available for 361 patients. RESULTS: The combined end point of cardiac death, myocardial infarction (MI), cerebrovascular accident, or re-vascularization occurred in 44 subjects. In the simple Cox model, leptin had a significant (p < 0.001) non-linear/cubic univariate relationship with the combined end point. Other variables associated with prognosis in the univariate analysis were body mass index (BMI), prior MI, insulin resistance, C-reactive protein (CRP), fibrinogen, and number of coronary vessels with >50% stenosis. A positive relationship between leptin and prognosis was also seen when leptin levels were split by quintiles, with a hazard ratio of 6.46 for the highest quintile. The only two variables significantly associated with the combined end point in the multivariate Cox model were leptin (p = 0.004) and number of coronary vessels with >50% stenosis (p < 0.001). A similar relationship between leptin and prognosis was observed when leptin was adjusted for BMI. CONCLUSIONS: In patients with angiographically confirmed coronary atherosclerosis, leptin is a novel predictor of future cardiovascular events independent of other risk factors, including lipid status and CRP.

Aged↗
PubMed2004

Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin.

BACKGROUND: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group to investigate means of improving the comparability of immunoassays for human chorionic gonadotropin (hCG), which was selected as a prototype glycoprotein analyte. The Working Group identified development of unambiguous nomenclature and production of new highly purified International Reference Reagents calibrated in substance concentrations as its primary objectives. METHODS: Preparations of intact hCG, nicked hCG, hCG beta-subunit, nicked hCG beta-subunit, hCG alpha-subunit, and hCG beta-core fragment were purified from a crude urinary hCG preparation, ampouled, lyophilized, and assigned values in substance concentrations (mol/L). Value assignment and accelerated degradation studies were carried out in accordance with WHO protocols for International Reference Reagents. RESULTS: The ampouled standards were assigned final values based on the recovery of immunoreactive material after reconstitution. The degradation studies showed that the standards were highly stable. CONCLUSIONS: The nomenclature of hCG-related molecules and immunoassays has been adopted by the IFCC, and the standards prepared and characterized by the Working Group have been formally adopted by the WHO as the First International Reference Reagents for six hCG-related molecules. These developments will enable better understanding of what assays for hCG measure and should ultimately help to improve the clinical application of these assays.

Chorionic Gonadotropin↗
PubMed2004

Personality disorder and social anxiety predict delayed response in drug and behavioral treatment of panic disorder.

BACKGROUND: The aim of this study was to analyze the impact of pretreatment characteristics and personality disorders on the onset of response in the treatment of panic disorder. METHODS: The data of 73 out-patients with panic disorder who had completed at least 6 weeks of a randomized trial of 24 weeks of either paroxetine only or paroxetine combined with cognitive group-therapy were analyzed in a Cox proportional hazards model. RESULTS: The likelihood of having responded to treatment (defined by a CGI rating of improvement) was more than twice as high for patients without a personality disorder or social phobia than for Patients with a personality disorder or social phobia. CONCLUSIONS: We suggest that patients with these characteristics do benefit from prolonged treatment, and they may profit from an additional treatment focused on social anxiety.

Adult↗
PubMed2004

Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This chapter about antithrombotic therapy during percutaneous coronary intervention (PCI) is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients undergoing PCI, we recommend pretreatment with aspirin, 75 to 325 mg (Grade 1A). For long-term treatment after PCI, we recommend aspirin, 75 to 162 mg/d (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend lower-dose aspirin, 75 to 100 mg/d (Grade 1C+). For patients who undergo stent placement, we recommend the combination of aspirin and a thienopyridine derivative (ticlopidine or clopidogrel) over systemic anticoagulation therapy (Grade 1A). We recommend clopidogrel over ticlopidine (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, we recommend use of a glycoprotein (GP) IIb-IIIa antagonist (abciximab or eptifibatide) [Grade 1A]. In patients undergoing PCI for ST-segment elevation MI, we recommend abciximab over eptifibatide (Grade 1B). In patients undergoing PCI, we recommend against the use of tirofiban as an alternative to abciximab (Grade 1A). In patients after uncomplicated PCI, we recommend against routine postprocedural infusion of heparin (Grade 1A). For patients undergoing PCI who are not treated with a GP IIb-IIIa antagonist, we recommend bivalirudin over heparin during PCI (Grade 1A). In PCI patients who are at low risk for complications, we recommend bivalirudin as an alternative to heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In PCI patients who are at high risk for bleeding, we recommend that bivalirudin over heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In patients who undergo PCI with no other indication for systemic anticoagulation therapy, we recommend against routine use of vitamin K antagonists after PCI (Grade 1A).

Abciximab↗
PubMed2003

Bivalirudin provides increasing benefit with decreasing renal function: a meta-analysis of randomized trials.

Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.

Adult↗