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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherothrombotic disease is a growing health problem, and is increasingly more costly to manage. Clopidogrel is an advanced, specific adenosine diphosphate receptor antagonist, which has been shown to be a highly potent antiplatelet agent. Data from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) study have demonstrated the significantly superior clinical benefit of clopidogrel over aspirin for secondary prevention of atherothrombotic disease, with a relative risk reduction in myocardial infarction, stroke or vascular death of 8.7% (95% confidence interval 0.3, 16.5; P = 0.043). Moreover, clopidogrel demonstrated an amplified clinical benefit versus aspirin in patients at high risk of atherothrombotic events, such as those with a previous history of symptomatic atherothrombotic disease or with major risk factors such as diabetes mellitus or hypercholesterolaemia. On the basis of commonly accepted threshold criteria (Euros 20000 per life-year gained; LYG), clopidogrel in comparison with aspirin is cost-effective for the secondary prevention of atherothrombotic disease (cost per LYG ranging from Euros 19462 to Euros 3256). Economic analyses have demonstrated consistent cost-effectiveness results with clopidogrel in different countries. Moreover, in high-risk patient subgroups the cost-effectiveness of clopidogrel in comparison with aspirin was evenbetter (cost per LYG ranging from Euros 5900 to Euros 6310). Compared with other treatment strategies used for the prevention of ischaemic or atherothrombotic events, the cost-effectiveness of clopidogrel in comparison with aspirin based on CAPRIE is favourable, with most analyses in the intermediate range of cost-effectiveness. The available data thus support the use of clopidogrel as a clinically efficient and cost-effective option for secondary prevention of atherothrombotic disease, particularly in high-risk patients.
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PMID:The value of clopidogrel versus aspirin in reducing atherothrombotic events: the CAPRIE study. 1587 9

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.
Diabetes 2005 Aug
PMID:Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. 1604 11

The prevention of diabetic retinopathy requires drugs that leverage the benefits of glycemic control without adding the burden of side effects. Aspirin at dosages of 1-1.5 g/day has prevented manifestations of diabetic retinal microangiopathy in a clinical trial as well as in studies with dogs. Because lower and safer doses of aspirin could be used if its beneficial effects on retinopathy were due to antithrombotic effects, we compared the effects of a selective antiplatelet drug (clopidogrel) to those of aspirin in streptozotocin-induced diabetic rats. Clopidogrel did not prevent neuronal apoptosis, glial reactivity, capillary cell apoptosis, or acellular capillaries in the retina of diabetic rats. Aspirin, at doses yielding serum levels (<0.6 mmol/l) well below the anti-inflammatory range for humans, prevented apoptosis of capillary cells and the development of acellular capillaries but did not prevent neuroglial abnormalities. The aldose reductase inhibitor sorbinil, used as the benchmark for the effect of the other drugs, prevented all abnormalities. The diabetic rat retina showed increased expression of the transcription factor CCAAT/enhancer-binding protein-beta, one of the known targets of low-intermediate concentrations of aspirin. Thus we found a spectrum of drug efficacy on the prevention of experimental diabetic retinopathy, ranging from the absent effect of a selective antiplatelet drug to the prevention of all abnormalities by an aldose reductase inhibitor. Aspirin at low-intermediate concentrations selectively prevented microangiopathy. The minimal effective dose of aspirin should now be sought.
Diabetes 2005 Dec
PMID:Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects. 1630 57

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

To assess gender-based differences in presentation and outcome after non-ST-elevation myocardial infarction (NSTEMI) in clinical practice, this study examined data from the Acute Coronary Syndrome registry, which enrolled 16,817 patients from 2000 through the end of 2002, 6,358 of them with NSTEMIs (34.1% women). Women with NSTEMIs were 7.5 years older, had a history of myocardial infarction and percutaneous coronary intervention or coronary artery bypass graft less often, and were less likely to have smoked. They more often had a history of systemic hypertension and diabetes mellitus, but this difference was due to their older age. Reperfusion therapy was performed less often in women, which still was significant after adjustment for baseline variables (odds ratio 0.71, 95% confidence interval 0.63 to 0.80). Clopidogrel was given less often in women (43.4% vs 56%). After adjustment for age, gender differences in medical therapy with statins, aspirin, and beta blockers were not significant. Hospital mortality was 1.7 times greater in women. This difference was not significant after adjustment for age (odds ratio 1.07, 95% confidence interval 0.84 to 1.35). Women had greater crude long-term mortality, but after age adjustment, this difference was no longer significant (odds ratio 0.92, 95% confidence interval 0.76 to 1.11). In conclusion, women with NSTEMIs were older than men and thus more often had concomitant diseases but less often had a history of myocardial infarction or coronary artery bypass grafts. They less often received acute percutaneous coronary intervention and less often were treated with clopidogrel. However, there was no difference in age-adjusted mortality in women.
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PMID:Gender differences in acute non-ST-segment elevation myocardial infarction. 1682 85

The optimal duration of treatment with clopidogrel after percutaneous coronary intervention (PCI) with stent placement remains controversial. The Randomized Argentine Clopidogrel Stent (RACS) trial was a prospective, randomized, nonblinded study of 1,004 patients undergoing PCI who were randomized after successful bare metal stent placement to 30 versus 180 days of clopidogrel; all patients also received aspirin. Patients were eligible regardless of whether they had presented with ST-elevation myocardial infarction (MI), acute coronary syndrome, or stable angina. The primary end point was a composite of death, MI, and stroke at 180 days. Baseline clinical characteristics showed no differences between groups in terms of age, gender, history, risk factors, or incidence of diabetes; 72% presented with an acute coronary syndrome and 15% had MI as the indication for PCI. At hospital discharge and 30 days, when the 2 groups received the same treatment, there were no significant differences between groups in frequency of death, MI, or stroke. However, from 30 days to 6 months, patients assigned to 6 months of clopidogrel reached the primary end point of death, MI, and stroke less frequently (4.99% vs 1.74%, p = 0.010, relative risk decrease 65%). No significant between-group differences were found in frequency of total bleeding (0.64% vs 1.52%, p = 0.34) for the control and study groups. In conclusion, after successful placement of a bare metal stent in a coronary artery, patients treated with 6 months of clopidogrel showed a trend toward fewer adverse events compared with those treated for 30 days.
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PMID:Long-term versus short-term clopidogrel therapy in patients undergoing coronary stenting (from the Randomized Argentine Clopidogrel Stent [RACS] trial). 1726 96

Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis. Major cardiovascular events cause about 80% of the total mortality in diabetic patients. Diabetes also induces peculiar microangiopathic changes leading to diabetic nephropathy conducive to end-stage renal failure, and to diabetic retinopathy that may progress to vision loss and blindness. In terms of major cardiovascular events, coronary heart disease and ischaemic stroke are the main causes of morbidity and mortality in diabetic patients. Peripheral arterial disease frequently occurs, and is more likely to be conducive to critical limb ischaemia and amputation than in the absence of diabetes. Although there are a number of differences in the pathogenesis and clinical features of diabetic macroangiopathy and microangiopathy, these two entities often coexist and induce mutually worsening effects. Endothelial injury, dysfunction and damage are common starting points for both conditions. Causes of endothelial injury can be distinguished into those 'common' to nondiabetic atherothrombosis, such as hypertension, dyslipidaemia, smoking, hypercoagulability and platelet activation; and those more specific and in some cases 'unique' to diabetes and directly related to the metabolic derangement of the disease, such as (i) desulfation of glycosaminoglycans (GAGs) of the vascular matrix; (ii) formation of advanced glycation end-products (AGE) and their endothelial receptors (RAGE); (iii) oxidative and reductive stress; (iv) decline in nitric oxide production; (v) activation of the renin-angiotensin aldosterone system (RAAS); and (vi) endothelial inflammation caused by glucose, insulin, insulin precursors and AGE/RAGE. Prevention of major cardiovascular events with the antithrombotic agent aspirin (acetylsalicylic acid) is widely recommended, but reportedly underutilised in patients with diabetes. However, some data suggest that aspirin may be less effective than expected in preventing cardiovascular events and especially mortality in patients with diabetes, as well as in slowing progression of retinopathy. In contrast, a recent study found picotamide, a direct thromboxane inhibitor, to be superior to aspirin in diabetic patients. Clopidogrel was either equivalent or less active in diabetic versus nondiabetic patients, depending upon different clinical settings.Recent studies have shown that some GAG compounds are able to reduce micro- and macroalbuminuria in diabetic nephropathy, and hard exudates in diabetic retinopathy, but it is as yet unknown whether these agents also influence the natural history of microvascular complications of diabetes. Lifestyle changes and physical exercise are also essential in preventing cardiovascular events in diabetic patients. Available data on the control of the metabolic state and the main risk factors show that careful adjustment of blood sugar and glycated haemoglobin is more effective in counteracting microvascular damage than in preventing major cardiovascular events. The latter objective requires a more comprehensive approach to the whole constellation of risk factors both specific for diabetes and common to atherothrombosis. This approach includes lifestyle modifications, such as dietary changes and smoking cessation and the use of HMG-CoA reductase inhibitors (statins), which are able to correct the lipid status and to prevent major cardiovascular events independently of the baseline lipidaemic or cardiovascular status. Tight control of hypertension is essential to reduce not only major cardiovascular events but also microvascular complications. Among antihypertensive measures, blockade of the RAAS by means of ACE inhibitors or angiotensin II receptor antagonists recently emerged as a potentially polyvalent approach, not only for treating hypertension and reducing cardiovascular events, but also to prevent or reduce albuminuria, counteract diabetic nephropathy and lower the occurrence of new type 2 diabetes in individuals at risk.
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PMID:Approaches to prevention of cardiovascular complications and events in diabetes mellitus. 1748 45

Recurrent ischemic stroke and transient ischemic attack are common problems in primary care, with stroke survivors averaging 10 outpatient visits per year. Risk factors such as hypertension, diabetes, and hypercholesterolemia should be evaluated during each office visit. Attention should be given to lifestyle modification including management of obesity, smoking cessation, reduction in alcohol consumption, and promotion of physical activity. The choice of an antiplatelet agent (e.g., aspirin, ticlopidine, clopidogrel, dipyridamole) or the anticoagulant warfarin is based on the safety, tolerability, effectiveness, and price of each agent. Aspirin is a common first choice for prevention of recurrent stroke, but the combination of dipyridamole and aspirin should be considered for many patients because of its superior effectiveness in two clinical trials. Clopidogrel is recommended for patients with aspirin intolerance or allergy, or for those who cannot tolerate dipyridamole. Warfarin and the combination of aspirin and clopidogrel should not be used in the prevention of ischemic stroke. Carotid endarterectomy is appropriate for select patients; carotid stenting was recently shown to be less effective and less safe than endarterectomy.
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PMID:Prevention of recurrent ischemic stroke. 1770 38

We investigated the incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 patients with diabetes mellitus and in 552 patients without diabetes mellitus (68% men and 32% women, mean age 66 +/- 14 y) who underwent percutaneous coronary intervention with stenting. Symptomatic chest pain was present in 95% of diabetics and in 95% of nondiabetics. Unstable symptoms were present in 67% of diabetics and in 68% of nondiabetics. Aspirin was used in 99% of diabetics and nondiabetics. Clopidogrel was used in 98% of diabetics and nondiabetics. Beta blockers were used in 85% of diabetics and nondiabetics. Lipid-lowering drugs were used in 96% of diabetics and in 95% of nondiabetics. In-hospital mortality occurred in 2 of 216 diabetics (0.9%) and in 2 of 552 nondiabetics (0.4%), P not significant. In-hospital mortality or nonfatal myocardial infarction or nonfatal stroke occurred in 3 of 216 diabetics (1.4%) and in 6 of 552 nondiabetics (1.1%), P not significant.
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PMID:Incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 diabetics and 552 nondiabetics undergoing percutaneous coronary intervention with stenting. 1789 Sep 30

The results obtained in the CAPRIE study in 1996 led to the introduction of the clopidogrel as a new antiplatelet drug in the secondary prevention of acute myocardial infarct (AMI), ischemic stroke (IS) and symptomatic peripheral artery disease (PAD). Clopidogrel showed a similar efficacy and safety than acetylsalicylic acid (ASA). More recently, the combined use of clopidogrel with ASA has evidenced a better protection than ASA alone in some patients: patients with past history of AMI, angina pectoris, intermittent claudication or PAD, IS or TIA, coronary bypass, and diabetes mellitus, patients on treatment with statins, and patients with symptomatic carotid stenosis >/=50%. We review the reported evidence on the efficacy of clopidogrel in the secondary prevention of ischemic stroke.
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PMID:Clopidogrel in secondary ischemic stroke prevention. 1853 62


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