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 risk factors, epidemiology, diagnosis, and treatment of peripheral arterial disease are reviewed. Peripheral arterial disease is characterized by a gradual reduction in blood flow to one or more limbs secondary to atherosclerosis. Risk factors include smoking, diabetes mellitus, hyperlipidemia, and hypertension. The most common clinical manifestation is intermittent claudication. The prevalence of intermittent claudication in people over the age of 50 is 2-7% for men and 1-2% for women. The ankle:brachial pressure index (ABPI) is a useful measure of disease severity; an ABPI of 0.5-0.9 is common in intermittent claudication. The goals of therapy are to relieve or reduce ischemic symptoms, alleviate disability, improve in functional capacity, prevent progression that may result in gangrene and limb loss, and prevent cardiovascular and cerebrovascular events. Treatment includes risk-factor modification, drug therapy (primarily with antiplatelet agents), and revascularization procedures. Aspirin has been shown to be effective in reducing the associated risk of myocardial infarction and stroke. Ticlopidine appears to be a reasonable alternative for patients who are hypersensitive to aspirin. Clopidogrel has been shown to be more effective than aspirin in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease. There is controversy over the appropriate treatment for acute arterial occlusions. Risk-factor modification and antiplatelet drugs are the mainstays of therapy for patients with intermittent claudication, the most common manifestation of peripheral arterial disease.
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PMID:Management of peripheral arterial disease. 978 99

The concept of a purinergic signalling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief historical review and update of purinoceptor subtypes, this article focuses on the diverse physiological roles of adenosine triphosphate, adenosine diphosphate, uridine triphosphate and adenosine. These molecules mediate short-term (acute) signalling functions in neurotransmission, secretion and vasodilation, and long-term (chronic) signalling functions in development, regeneration, proliferation and cell death. Plasticity of purinoceptor expression in pathological conditions is frequently observed, including an increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction, and in sympathetic cotransmitter control of blood vessels in hypertensive rats. The antithrombotic action of clopidogrel (Plavix), a P2Y12 receptor antagonist, has been shown to be particularly promising in the prevention of recurrent strokes and heart attacks in recent clinical trials (CAPRIE and CURE). The role of P2X3 receptors in nociception and a new hypothesis concerning purinergic mechanosensory transduction in visceral pain will be considered, as will the therapeutic potential of purinergic agonists or antagonists for the treatment of supraventricular tachycardia, cancer, dry eye, bladder hyperactivity, erectile dysfunction, osteoporosis, diabetes, gut motility and vascular disorders.
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PMID:Potential therapeutic targets in the rapidly expanding field of purinergic signalling. 1187 39

Treatment of acute coronary syndrome is under rapid progress. Nevertheless, the early complication rate remains high. Standard antithrombotic treatment is Aspirin 100 mg/d. Patients with elevated risk should be treated with Aspirin and Clopidogrel if primary invasive strategy ist not intended. Independent of the cholesterol level, statins should be given in the early phase of acute coronary syndrome. Dose adaptation is recommended after three months corresponding to the national guidelines. Mainly in diabetes mellitus, additional treatment with an ACE inhibitor lowers the overall cardiovascular risk also in patients without arterial hypertension or congestive heart failure. Six months after the acute event, risk stratification should be adapted.
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PMID:[Secondary prevention after acute coronary syndrome--role of modern drug therapy]. 1188 56

Accelerated atherosclerosis and the increased risk of thrombotic vascular events in diabetes may result from dyslipidemia, endothelial dysfunction, platelet hyperreactivity, an impaired fibrinolytic balance, and abnormal blood flow. There is also a correlation between hyperglycemia and cardiovascular (CV) events. The importance of platelets in the atherothrombotic process has led to investigation of using antiplatelet agents to reduce CV risk. A meta-analysis conducted by the Antiplatelet Trialists' Collaboration demonstrated that aspirin reduced the risk of ischemic vascular events as a secondary prevention strategy in numerous high-risk groups, including patients with diabetes. Based on results from placebo-controlled randomized trials, the American Diabetes Association recommends low-dose enteric-coated aspirin as a primary prevention strategy for people with diabetes at high risk for CV events. Clopidogrel is recommended if aspirin allergy is present. There is occasionally a need for an alternative to aspirin or for additive antiplatelet therapy. Aspirin in low doses inhibits thromboxane production by platelets but has little to no effect on other sites of platelet reactivity. Agents such as ticlopidine and clopidogrel inhibit ADP-induced platelet activation, whereas the platelet glycoprotein (Gp) IIb/IIIa complex receptor antagonists block activity at the fibrinogen binding site on the platelet. These agents appear to be useful in acute coronary syndromes (ACSs) in diabetic and nondiabetic patients. A combination of clopidogrel plus aspirin was more effective than placebo plus standard therapy (including aspirin) in reducing a composite CV outcome in patients with unstable angina and non-ST segment elevation myocardial infarction. In a meta-analysis of six trials in diabetic patients with ACSs, intravenous GpIIb-IIIa inhibitors reduced 30-day mortality when compared with control subjects. Results from controlled prospective clinical trials justify the use of enteric-coated low-dose aspirin (81-325 mg) as a primary or secondary prevention strategy in adult diabetic individuals (aged >30 years) at high risk for CV events. Recent studies support the use of clopidogrel in addition to standard therapy, as well as the use of GpIIb-IIIa inhibitors in ACS patients.
Diabetes Care 2003 Jul
PMID:The platelet in diabetes: focus on prevention of ischemic events. 1283 32

Elderly patients with unstable angina pectoris/non-ST-segment elevation myocardial infarction should be hospitalized. Precipitating factors should be identified and corrected. Electrocardiogram monitoring is important. Aspirin should be given as soon as possible and continued indefinitely. Clopidogrel should given for up to 9 months in patients in whom an early noninterventional approach is planned or in whom a percutaneous coronary intervention (PCI) is planned. Clopidogrel should be withheld for 5-7 days in patients in whom elective coronary artery bypass graft surgery (CABGS) is planned. A platelet glycoprotein IIb/IIIa inhibitor should also be given in addition to aspirin, clopidogrel, and heparin in patients in whom cardiac catheterization and PCI are planned. Patients whose symptoms are not fully relieved with three 0.4-mg sublingual nitroglycerin tablets or spray taken 5 minutes apart and the initiation of an intravenous beta blocker should be treated with continuous intravenous nitroglycerin. Beta blockers and angiotensin-converting enzyme (ACE) inhibitors should be given and continued indefinitely. The benefit of long-acting nondihydropyridine calcium channel blockers is limited to symptom control. Intra-aortic balloon pump counterpulsation should be used for severe ischemia that is continuing or occurs frequently despite intensive medical therapy or for hemodynamic instability. Statins should be used if the serum low-density lipoprotein (LDL) cholesterol is >or=100 mg/dl and continued indefinitely. Enoxaparin is preferable to intravenous unfractionated heparin in the absence of renal failure and unless CABGS is planned within 24 hours. Thrombolysis is not beneficial. High-risk patients should have an early invasive strategy with CABGS or PCI performed depending on the coronary artery anatomy, left ventricular function, presence or absence of diabetes, and findings on noninvasive testing. Following hospital discharge, patients should have intensive risk factor modification with cessation of smoking, maintenance of blood pressure below 135/85 mmHg, indefinite use of statins if needed to maintain the serum LDL cholesterol <100 mg/dl, intensive control of diabetes, maintenance of optimal weight, and daily exercise. Patients should be treated indefinitely with aspirin, beta blockers, and ACE inhibitors and with clopidogrel for up to 9 months. Nitrates should be given for ischemic symptoms. Hormonal therapy should not be given to postmenopausal women.
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PMID:Treatment of unstable angina pectoris/non-ST-segment elevation myocardial infarction in elderly patients. 1457 Aug 61

Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with atherosclerotic vascular disease was more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death. In the setting of coronary stenting, a double regimen including aspirin and ticlopidine or clopidogrel has proved more effective in the prevention of in-stent thrombosis than aspirin alone. Chronic oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa has been largely disappointing.
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PMID:Role of antiplatelet drugs in the prevention of cardiovascular events. 1459 62

Risk factors for stroke should be evaluated in patients who have had a transient ischemic attack. Blood pressure, lipid levels, and diabetes mellitus should be controlled. When applicable, smoking cessation and weight loss also are important. Angiotensin-converting enzyme inhibitor therapy may help prevent stroke. Aspirin is the treatment of choice for stroke prevention in patients who do not require anticoagulation. Clopidogrel is an alternative therapy in patients who do not tolerate aspirin. Atrial fibrillation, a known cardioembolic source (confirmed thrombus), or a highly suspected cardioembolic source (e.g., recent large myocardial infarction, dilated cardiomyopathy, mechanical valve, rheumatic mitral valve stenosis) are indications for anticoagulation.
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PMID:Transient ischemic attacks: Part II. Treatment. 1610 Aug 52

Clopidogrel has been evaluated in clinical trials that included cardiovascular patients with different risk levels for a cardiovascular event. We reviewed the results of the Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events (CAPRIE) and Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trials, with special emphasis on comparing the outcomes in high-risk patients with those of the total populations in the trials. The results in the high-risk subgroups and total populations were compared by recording total event rates, absolute risk reduction, relative risk reduction, and number needed to treat. In the CAPRIE trial, the efficacy of clopidogrel was compared with acetylsalicylic acid (ASA) in the following subgroups: total population, previous coronary bypass surgery, history of more than 1 ischemic event, multiple vascular beds involvement, diabetes, and hypercholesterolemia. In the CURE trial, the combination of clopidogrel and ASA was compared with ASA alone. The results in the CURE study were compared in patients who did and did not have a coronary intervention procedure, in patients with different levels of risk based on the Thrombolysis in Myocardial Infarction score and in patients with and without a history of a revascularization procedure. High-risk subgroups of patients participating in the CAPRIE and CURE studies were more responsive to the beneficial effects of clopidogrel compared with the study population as a whole. High-risk groups in the CAPRIE and CURE studies would be expected to derive enhanced benefit from treatment with clopidogrel over that achieved by ASA.
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PMID:Comparative benefits of clopidogrel and aspirin in high-risk patient populations: lessons from the CAPRIE and CURE studies. 1595 13

Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.
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PMID:Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke. 1573 10

Ischaemic stroke and other atherothrombotic events substantially increase the medico-economic burden because of their high treatment costs and long-lasting disabilities with need for chronic care. Studies have shown that the cost of stroke represents approximately 3 - 5% of the annual health budget. Antiplatelet agents play a major role in secondary stroke prevention. Acetylsalicylic acid (ASA), ASA combined with extended-release dipyridamole (ER-Dip), and clopidogrel are all acceptable choices for first-line treatment in the secondary prevention of stroke. The newer antiplatelets, however, are more expensive than ASA, and their cost-effectiveness is not easily estimated. ASA has to be given to 33 stroke patients to prevent one future stroke, myocardial infarction (MI) or vascular death compared with placebo. Adding ER-Dip to ASA increases the benefit for the patients. A total of 33 stroke patients had to be treated with this combination, instead of ASA, to prevent one stroke. However, the combination of ASA plus ER-Dip does not prevent MI, vascular death or the combined end point of either stroke or death. Clopidogrel is more effective than ASA in preventing a combined end point of ischaemic stroke, MI, or vascular death, but it has not been shown to be superior to ASA in preventing recurrent stroke in transient ischaemic attack or stroke patients. Several subgroups, such as stroke patients with additional peripheral artery disease, patients with prior coronary artery bypass, patients with insulin-dependent diabetes, and patients with recurrent vascular events, were identified, in whom the benefit of clopidogrel is amplified. Taking economical aspects into account, the fixed combination of ASA and ER-Dip can be recommended for secondary stroke prevention as a first-line alternative to ASA in patients without major comorbidity. In patients with higher comorbidity, clopidogrel may be more effective for the individual patient compared with ASA, and might also be cost-effective. Furthermore, in patients with ASA intolerance clopidogrel is a useful, but expensive, alternative.
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PMID:Efficacy and costs of secondary prevention with antiplatelets after ischaemic stroke. 1579 27


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