Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. The secondary triple composite endpoint (death, MI, urgent repeat revascularization) occurred in 7.6% of patients in the bivalirudin group compared with 7.1% of patients in the UFH plus GP IIb/IIIa inhibitor group. Both endpoints met formal statistical criteria for noninferiority to UFH plus GP IIb/IIIa inhibitor. By imputed comparison from historic GP IIb/IIIa trials between bivalirudin versus UFH alone, REPLACE-2 demonstrated that bivalirudin was superior to UFH alone with respect to the quadruple and triple composite endpoints. Furthermore, bivalirudin plus provisional GP IIb/IIIa blockade was associated with a significant reduction in in-hospital bleeding (2.4% vs. 4.1%; p < 0.001). At 6 months' follow-up, there was no significant difference in rates of death, MI, or revascularization between the two groups. Furthermore, there was no evidence that the early, nonsignificant 0.5% excess non-Q-wave MI in the bivalirudin group translated into later mortality. There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.
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PMID:Bivalirudin in PCI: an overview of the REPLACE-2 trial. 1528 55

Diabetes mellitus is an increasingly prevalent condition in the modern era. Coronary artery disease is the major cause of mortality in this population. Despite advances in the therapeutic modalities available for management of coronary artery disease, diabetic patients tend to have worse short and long term outcomes. Acute coronary syndrome in this patient population should be managed aggressively with antithrombotic and antiplatelet agents, as well as early mechanical reperfusion strategies. Diabetic patients presenting with acute coronary syndrome benefit from intensive glycemic control in the first 48 hours. Percutaneous coronary angioplasty using drug-eluting stents with concomitant glycoprotein IIb/IIIa inhibitors should be considered early in diabetic patients with single vessel and multivessel disease. Long-term preventive measures include aspirin, clopidogrel, statins and angiotensin- converting enzyme inhibitors.
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PMID:Management of acute coronary syndrome in diabetes mellitus. 1534 Jul 40

Advances in percutaneous coronary revascularization have meant that, increasingly, patients with multivessel diseases are initially treated with the methods of interventional cardiology. Ongoing studies involving new stent coatings and optimized anti-thrombotic therapies could help to lower future restenosis rates and improve the success rate of stenting. Thrombocyte glycoprotein IIb/IIIa receptor blockers have already been shown to reduce the rate of acute PTCA complications in high-risk patients and could have a sustained impact on the long-term prognoses for PTCA patients. However, for diabetic patients with coronary multivessel diseases, coronary artery bypass grafting using arterial grafts as the initial revascularization method must be given preference over other therapy methods. Consequently, this group of patients is bound to grow in importance in cardiac surgery. The advances made in percutaneous coronary revascularization and in coronary surgery call for further prospective, controlled, randomized clinical studies in order to establish the best possible treatment strategy for patients with diabetes. It should be noted, however, that the therapeutic effect of myocardial revascularization is generally limited to individual coronary-arterial segments, whereas the pathological process of atherosclerosis is rather diffuse. The surgical strategy should therefore be seen as part of an overall strategy which encompasses other forms of treatment (e.g. intensive efforts to improve control of blood glucose level, blood pressure, and cholesterol level) in order to arrest the general progression of the disease and to reduce the risk of myocardial infarction and death.
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PMID:Diabetes mellitus in coronary artery surgery: therapeutic strategies in the light of recent studies. 1557 76

Coronary disease accounts for the majority of deaths among patients with diabetes and the thrombotic milieu accelerated by diabetes results in unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as part of an early invasive approach is preferred. However substantial numbers of patients present to rural or non-teaching hospitals without immediate access to a catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2 production and platelet activation together present an extensive thrombotic challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors when used without PCI. Heterogeneity of platelet aggregometric analysis may have identified GP IIb/IIIa doses used in clinical trials that may not fully overcome the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to demonstrate a difference in mortality when used without PCI. The PURSUIT trial provided evidence that eptifibatide decreases death or non-fatal myocardial infarction (MI) in the main group and in the diabetic subgroup. Reductions in this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia at 48 h or 7 days in the main cohort but not specifically in patients with diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising the question of whether these agents should be used at all without PCI. Variability in experimental methodology of platelet aggregometry and selection of anticoagulant used during dose finding studies may have generated doses that are insufficient to overcome the thrombotic burden. A new marker of active inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors in patients with diabetes experiencing UA/NSTEMI.
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PMID:Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction. What have we learned in the last 10 years? 1558 37

It has been previously demonstrated that diabetics are less sensitive to heparin compared to non-diabetics. We hypothesized that an initial heparin dose of 80 IU per kilogram administered to diabetics rather than 70 IU per kilogram might yield a more optimal initial ACT of 300 to 350 seconds when glycoprotein IIb/IIIa receptor antagonists are not used. We prospectively studied 130 elective PCI patients without diabetes treated with 70 IU per kilogram of unfractionated heparin and 81 elective PCI patients with diabetes treated with 80 IU per kilogram, and compared the initially achieved ACT. The mean heparin dose given per kg was greater (by intention) in diabetics versus non-diabetics. Despite that, there was no significant difference in the initially achieved ACT in diabetics and non-diabetics.
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PMID:New heparin dosing regimen for diabetics undergoing percutaneous coronary intervention. 1587 3

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.
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PMID:Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events). 1618 16

Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 micromol/L) and collagen (6 microg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 micromol/L) and thrombin receptor-activating peptide (50 micromol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.
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PMID:Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention. 1637 81

There is an increase in arterial thrombotic events in the elderly. Elderly patients are more likely to have associated diseases, such as diabetes, hypertension and hypercholesterolemia, and when age is confounded by these other predisposing factors, the risk of an arterial ischemic event increases disproportionately. Antithrombotic therapy for geriatric patients is underused, even when one adjusts for potential drug contraindications. This article focuses on the action of the currently available antiplatelet agents--aspirin, clopidogrel, and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists, and assesses their effects in different disease states, with special attention to data that examine the geriatric population.
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PMID:Antiplatelet agents and arterial thrombosis. 1637 67

Patients with diabetes who undergo percutaneous coronary intervention (PCI) are at high risk for thrombotic complications following the procedure. We sought to compare the anti-thrombotic effect of bivalirudin to that of eptifibatide plus unfractionated heparin in diabetic patients undergoing elective PCI. Thirty diabetic patients were randomized to receive during PCI either bivalirudin (bivalirudin group, n=15) or eptifibatide plus heparin (eptifibatide group, n=15) at standard dosing regimens. The drugs were continued for 20 minutes (bivalirudin) or 18 hours (eptifibatide) after PCI. Blood thrombogenicity was assessed using the Badimon ex vivo perfusion chamber. Each patient underwent two perfusion studies - at baseline (on aspirin and clopidogrel) and 15-20 minutes following PCI. Perfusion studies were performed at rheologic conditions of low and high shear rates (LSR, HSR). Porcine aortic tunica media served as the thrombogenic substrate. Aortic specimens were stained for total platelet-thrombus and fibrin deposition. Thrombus area was measured using computerized planimetry. There were no differences in clinical characteristics or baseline thrombus area between the two groups. Total platelet-thrombus area was reduced significantly in both groups, but the degree of reduction was lower in the bivalirudin group compared with the eptifibatide group (HSR: 69.5% vs. 89.3% reduction, respectively, P=0.04; LSR: 50.6% vs. 73.2%, P=0.03). Fibrin deposition was reduced in both groups by 47-49%. In conclusion, both bivalirudin and the combination of eptifibatide plus heparin, given to diabetic patients during PCI, achieved marked reductions in total thrombus formation and fibrin deposition. However, glycoprotein IIb/IIIa inhibition by eptifibatide caused a more pronounced reduction in thrombus formation.
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PMID:Anti-thrombotic effect of bivalirudin compared with eptifibatide and unfractionated heparin in diabetic patients: an ex vivo human study. 1652 71

Patients with diabetes mellitus are often not recognized in clinical routine, but also not well characterized in clinical trials. As a diagnostic approach it is recommended to test fasting glucose and glycosylated hemoglobin (HbA1c) in every patient with coronary artery disease (CAD). HbA1c, in addition, provides important prognostic information. Patients with diabetes mellitus do have an enhanced cardiovascular risk in all stages and during all kind of interventions of CAD. However, diabetes is not equal to diabetes; risk modifying factors such as HbA1c, concomitant diseases and medication have to be considered. Absolute benefit of pharmacological therapies is also enhanced in patients with diabetes compared to non-diabetics. However, statins or anti-hypertensive treatment seem to be even more effective in reducing cardiovascular events than pure control of glucose levels alone. During percutaneous interventions (PCI) glycoprotein IIb/IIIa-inhibitors reduce mortality in diabetics, an effect which may be partially also achieved by Clopidogrel. Glitazones reduce restenosis rates; however, clinical end point studies are still ongoing. After PCI, restenosis may be a predictor of mortality in patients with diabetes. Whether drug eluting stents, besides effectively reducing restenosis, may also reduce hard clinical events in patients with diabetes remains to be demonstrated. Current available studies comparing PCI with bypass are limited due to not considered factors (stenosis morphology), randomization bias, and faster progress of technology compared to study termination. During an acute coronary syndrome/myocardial infarction, hyperglycemia is an adverse prognostic marker. However, so far studies using glucose-insulin-potassium (GIK) infusion have not been convincingly demonstrate to be beneficial.
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PMID:[Diabetes mellitus and coronary artery disease--a high risk combination]. 1659 43


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