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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Older individuals contribute heavily to the percentage of deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is highest in subjects > 65 years. Prospective intervention trials involving groups of clinically comparable subjects > or = 60 allow the following statements to be made with regard to the use of antithrombotic drugs in the elderly. Antiplatelet agents. To prevent recurrence of ischaemic stroke and MI in stable/unstable angina, MI, TIA/stroke or peripheral arterial disease, aspirin is the drug of choice. Clopidogrel is more effective than aspirin in this respect. Heparin. For the treatment of acute deep venous thrombosis (DVT) and pulmonary embolism (PE), intravenous standard heparin or subcutaneous standard heparin are effective (aPTT 1.5-2.0 times baseline values). As the risk of bleeding increases with age, low-molecular-weight heparins (LMWH) are preferable in the elderly. For the prophylaxis of VTE in general surgery in subjects at low-moderate risk, low-dose heparin or low doses of LMWH are effective. In subjects at high risk, adjusted-dose heparin plus physical devices or high-dose LMWH are recommended. The combination of heparin and aspirin is the standard treatment for unstable angina and non-Q wave MI. LMWH are as active as standard heparin in this indication. Vitamin K antagonists. For the chronic treatment of VTE, warfarin is also the treatment of choice (INR 2.0-3.0) in the elderly, though lower doses are needed due to their hypersensitivity to oral anticoagulants. For the prevention of thromboembolic stroke in patients > 75 with atrial fibrillation, warfarin is the drug of choice. Patients aged 65-75 may receive warfarin or aspirin. Thrombolytic agents. Thrombolytic agents are not recommended for treating DVT in the elderly because of their limited risk/benefit ratio and should be confined to massive PE. In the absence of contraindications, thrombolysis for MI may be considered in the elderly.
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PMID:Antithrombotic drugs for older subjects. Guidelines formulated jointly by the Italian Societies of Haemostasis and Thrombosis (SISET) and of Gerontology and Geriatrics (SIGG). 1138 24

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in term of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some endpoints, it is superior to aspirin. Due to its side effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 can not be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.
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PMID:Antithrombotic Secondary Prevention After Stroke. 1148 59

(1) Clopidogrel, an antiplatelet drug chemically similar to ticlopidine, is marketed in France for secondary prevention of thrombotic complications in patients with a history of myocardial infarction, ischaemic stroke or peripheral arterial disease. (2) Marketing authorisation was based mainly on the CAPRIE trial, a study that involved 19,815 patients. In this trial of secondary cardiovascular prevention, clopidogrel was slightly more effective than aspirin (325 mg/day) according to a statistical analysis of a combined end point (ischaemic stroke, or myocardial infarction, or death of vascular causes). The difference was more marked in the subgroup of patients with obstructive arterial disease of the lower limbs. (3) Clopidogrel was well tolerated in this trial. The only adverse effects more frequent on clopidogrel than on aspirin were rash and diarrhoea. (4) Clopidogrel showed no haematological toxicity, an adverse effect that restricts the use of ticlopidine. (5) The lack of long-term follow-up in real clinical settings prevents any meaningful estimation of the safety profile or of the risk of drug interactions.
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PMID:Clopidogrel: new preparation. An alternative to aspirin. 1150 10

As a result of medical progress each year numerous new therapies are introduced to the medical community, and each of them must prove its usefulness in two arenas. Firstly, does the new therapy improve outcomes relative to conventional therapy? If this test is passed, the second question is: are the improved outcomes worth the extra costs? Controlled clinical trials answer the first question and economic analysis, the second. The CARPIE-Study has proven, that Clopidogrel, a new antiplatelet drug, was superior in secondary prevention of cardiovascular events to aspirin. On the basis of this study we conducted a cost-effectiveness analysis from the perspective of Swiss third party payers. The following costs were included in the analysis: treatment costs of aspirin and clopidogrel, myocardial infarction, ischaemic stroke and primary non-fatal intracranial haemorrhage. For the calculation of the years of life gained the DEALE-method was applied. The net costs of treating 1000 patients, i.e. incremental drug costs less savings of treatment costs, are Fr. 1.5 Mio. The intervention with Clopidogrel lead to an additional gain of 63 life years in compared to aspirin. At additional yearly cost of Fr. 722.--per patient the analysis yield a cost-effectiveness of CHF 24,164 (nominal) Fr. 22,837 (discounted) per additional year of live saved. The results suggest that the cost-effectiveness of Clopidogrel in secondary prevention lie well within the range of other preventive cardiovascular interventions. Therefore, from an economic perspective the use of Clopidogrel in secondary prevention of major cardiovascular events in patients with atherosclerotic vascular disease is justifiable.
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PMID:[Cost effectiveness of clopidogrel in secondary cardiovascular prevention: a cost-effectiveness analysis based on the Caprie Study]. 1155 Jun 19

The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine) versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042). Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern.
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PMID:Is clopidogrel superior to aspirin in secondary prevention of vascular disease? 1171 29

Peripheral arterial disease (PAD) is a major risk marker for systemic ischaemic events. The understanding of PAD has moved from PAD as an organ-specific disease to PAD as the lower-limb localization of a multifocal disease, i.e. atherothrombosis. Blood platelet activation and aggregation is a common denominator in atherothrombotic events, and use of antiplatelet agents in patients with PAD can inhibit thrombus formation and reduce the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and vascular death. Many studies have investigated various antiplatelet regimens for preventing acute cardiovascular events in patients with a prior ischaemic event, although many of these studies had a number of limitations. The Antiplatelet Trialists' Collaboration performed a meta-analysis of 23 stroke trials and found an average odds risk reduction of 25% for a combined endpoint of stroke, MI or vascular death. The concept of atherothrombosis as a multifocal disease was challenged by the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial. This study showed an 8.7% decrease in the relative risk reduction for further atherothrombotic events with clopidogrel over aspirin (p = 0.043) for the overall population, in terms of the combined endpoint of IS, Ml or vascular death.
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PMID:Rationale for the use of platelet aggregation inhibitors in PAD patients. 1178 61

The principal pathophysiological mechanism in patients with unstable angina pectoris (UAP) and non-Q-wave myocardial infarction (NQMI) is atherothrombosis--the formation of a platelet-rich thrombus at the site of a disrupted or eroded atherosclerotic plaque. Despite standard therapy, which includes intravenous heparin or low-molecular-weight heparin and acetylsalicylic acid (ASA) during the acute phase followed by ASA on a long-term basis, the prognosis for patients remains poor. The efficacy of early and long-term treatment with clopidogrel (clopidogrel bisulphate) on top of standard therapy including ASA has recently been tested in patients with UAP and NQMI. In the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischaemic Events) Trial, more than 12,500 patients were randomized, in a double-blind manner, to receive placebo or clopidogrel, given as an initial 300-mg loading dose, followed by a 75-mg daily dose. All patients received a recommended dose of ASA (75-325 mg daily). The mean duration of treatment and follow-up was 9 months (minimum 3 months, maximum 12 months). CURE clearly showed that clopidogrel reduced the risk of a composite of cardiovascular death, stroke and MI, with a relative risk reduction of 20% (95% confidence interval, 72-90%; p < 0.001). The protective effect of clopidogrel was apparent within 2 h of initiation of therapy, and the benefit was consistent at 30 days and after long-term treatment. The benefit of clopidogrel was observed across the spectrum of high- and low-risk patients and was obtained with an acceptable risk of bleeding and no increase in intracranial haemorrhage. Based on data from CURE, the use of clopidogrel on top of standard therapy including ASA can be expected to become the new foundation therapy in patients with UAP and NQMI.
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PMID:Insights from CURE: using clopidogrel on top of standard therapy. 1180 83

Patients with a clinical manifestation of atherothrombosis such as a recent ischaemic cerebrovascular event are at high risk of subsequent events. Atherothrombosis often reflects disseminated disease; thus, further events may occur not only in the same arterial distribution but also in other vascular beds. To achieve adequate secondary prevention in these patients, long-term antiplatelet therapy with consistent benefit across the atherothrombosis spectrum is required. In the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) Trial, clopidogrel (clopidogrel bisulphate) was superior to acetylsalicylic acid (ASA) in reducing the combined risk of ischaemic stroke (IS), myocardial infarction (MI) or vascular death in patients with symptomatic atherosclerosis. Post hoc analyses demonstrated that the benefit of clopidogrel was amplified in high-risk patients, including patients with a history of previous ischaemic events, diabetic patients and patients with hypercholesterolaemia. The synergistic antiplatelet effect produced by using clopidogrel on top of ASA may be beneficial in high-risk patients. The benefit of dual antiplatelet therapy was recently examined in the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) Study, which demonstrated that long-term treatment with clopidogrel on top of standard therapy including ASA was superior to standard therapy alone in the prevention of major vascular ischaemic events in patients with unstable angina or non-Q-wave MI. The ongoing MATCH (Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke) trial will evaluate the efficacy and safety of clopidogrel plus ASA versus clopidogrel alone in patients with recent transient ischaemic attack (TIA) or IS and with at least one additional risk factor. Approximately 7,600 patients will be enroled, with treatment and follow-up for each patient lasting 18 months. The primary combined efficacy endpoint will be the first occurrence of an event in the composite of IS, MI, vascular death or rehospitalization for an acute ischaemic event during the follow-up period. MATCH will explore the potential benefit of clopidogrel in high-risk stroke/TIA patients and together with CAPRIE and CURE could provide further evidence of the long-term benefit of clopidogrel in patients with major atherothrombotic manifestations.
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PMID:From CURE to MATCH: ADP receptor antagonists as the treatment of choice for high-risk atherothrombotic patients. 1180 84

Older individuals (subjects aged >65 years) largely contribute to the percentage deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is also higher >65 years old patients. However, the risk of bleeding complications in patients on antithrombotic drugs increases with age and with clinical conditions, as cognitive/psychiatric diseases, traumas, hypertension, poor compliance with medications, common in the elderly. Thus the risk-benefit ratio of antithrombotics should be carefully evaluated in older individuals. To prevent the risk and the recurrence of ischemic stroke and MI in the older patients with stable/ unstable angina, MI, TIA/stroke or peripheral arterial disease, antiplatelet drugs are of choice. Aspirin is the most widely used antiplatelet drug. Clopidogrel is safer and more effective than aspirin in this respect. The combination of heparin and aspirin is the treatment of choice for unstable angina and non-Q wave MI, also in the elderly. Low molecular weight heparins (LMWHs) proved to be as effective as standard heparin in this indication. In the absence of contraindications, thrombolysis for treatment of acute MI may be considered in the elderly. For the treatment of acute venous thromboembolism (VTE), intravenous standard heparin, subcutaneous standard heparin or LMWHs are effective. Because of the limited risk/benefit ratio, thrombolytic agents are not recommended for treating deep vein thrombosis (DVT) in the elderly. They should be limited to young patients and to patients with massive pulmonary embolism (PE). For chronic treatment of VTE, warfarin is the treatment of choice (INR 2.0-3.0), also in the elderly. Because of hypersensitivity to oral anticoagulants, lower dosages of warfarin are needed in the old patient. As to prophylaxis of VTE in surgery, in subjects at low-moderate risk, or in medical patients, low-dose heparin or low-dose LMWHs are effective. As to prophylaxis of VTE in surgery in subjects at high risk, adjusted-dose heparin or high-dose LMWHs are recommended. Finally, as to prevention of stroke in patients older than 75 with atrial fibrillation (AF), warfarin is of choice.
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PMID:The use of antithrombotic drugs in older people. 1185 Jun 11

The standard approach to preventing acute coronary syndromes (ACSs)has been to inhibit platelet aggregation with aspirin and to inhibit blood coagulation with low molecular-weight heparin (LMWH). Even with this combination there is still a substantial short and long-term cardiovascular risk. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial [1] compared clopidogrel plus aspirin against aspirin alone in patients with ACSs. The clopidogrel regimen was a loading dose of 300 mg p.o. followed by 75 mg/day and the recommended dose of aspirin was 75 - 325 mg/day. The first primary outcome was a composite of death from cardiovascular causes, non-fatal myocardial infarction (MI) or stroke and this occurred significantly less often in the clopidogrel than the placebo group (9.3 vs. 11.4%). Although there were more clopidogrel patients with life-threatening bleeding (clopidogrel 2.2%, placebo 1.8%), this represented GI haemorrhages and bleeding at sites of arterial puncture rather than fatal bleeding. This trial suggests a role for clopidogrel in the long-term treatment of ACSs.
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PMID:Clopidogrel: a CURE in acute coronary syndromes? 1186 84


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