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Biomedical subjects

C L Sudlow

Publications and source records attributed to C L Sudlow.

7 recordsLinked to original sources
PubMed2000

Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients.

BACKGROUND: The most widely studied and prescribed antiplatelet agent for the prevention of stroke and other serious vascular events among high vascular risk patients is aspirin. Aspirin inhibits platelet activation by inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of a serious vascular event by about a quarter. The thienopyridines (ticlopidine and clopidogrel) inhibit platelet activation by a different mechanism to aspirin (blocking the ADP receptor on platelets), and so may be more effective than aspirin. OBJECTIVES: The objective of this review was to determine the effectiveness and safety of thienopyridine derivatives (ticlopidine and clopidogrel) versus aspirin for the prevention of serious vascular events (stroke, myocardial infarction (MI) or vascular death) in patients at high risk of such events, and specifically in patients with a previous TIA or ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (most recent search: March 1999) and the Antithrombotic Trialists' database, and also contacted Sanofi pharmaceutical company. SELECTION CRITERIA: All unconfounded, double blind, randomised trials directly comparing ticlopidine or clopidogrel with aspirin in high vascular risk patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Additional data were sought from the principal investigators of the largest trial. MAIN RESULTS: Four trials involving a total of 22,656 high vascular risk patients were included. The trials were of high quality and comparable. Aspirin was compared with ticlopidine in three trials (3471 patients) and with clopidogrel in one trial (19,185 patients). Allocation to a thienopyridine was associated with a modest, yet statistically significant, reduction in the odds of a serious vascular event (12. 0% vs 13.0%; OR: 0.91, 95% CI: 0.84 to 0.98; 2p = 0.01), corresponding to the avoidance of 11 (95% CI: 2 to 19) serious vascular events per 1000 patients treated for about two years. There was also a reduction in stroke (5.7% vs 6.4%; OR: 0.88, 95% CI: 0.79 to 0.98; 7 [95% CI: 1 to 13] strokes avoided per 1000 patients treated for two years). Compared with aspirin, thienopyridines produced a significant reduction in the odds of gastrointestinal haemorrhage and other upper gastrointestinal upset, but a significant increase in the odds of skin rash and of diarrhoea. However, the increased odds of skin rash and diarrhoea were greater for ticlopidine than for clopidogrel. Allocation to ticlopidine, but not clopidogrel, was associated with a significant increase in the odds of neutropenia (2.3% vs 0.8%; OR: 2.7, 95% CI: 1.5 to 4.8). In the subset of patients with TIA/ischaemic stroke, the results were similar to those for all patients combined. However, since these patients are at particularly high risk of stroke, allocation to a thienopyridine was associated with a larger absolute reduction in stroke (10.4% vs 12.0%; OR: 0.86, 95% CI: 0.75 to 0.97; 16 [95% CI: 3 to 28] strokes avoided per 1000 patients treated for two years). REVIEWER'S CONCLUSIONS: The available randomised evidence shows that the thienopyridine derivatives are modestly but significantly more effective than aspirin in preventing serious vascular events in patients at high risk (and specifically in TIA/ischaemic stroke patients), but there is uncertainty about the size of the additional benefit. The thienopyridines are also associated with less gastrointestinal haemorrhage and other upper gastrointestinal upset than aspirin, but an excess of skin rash and diarrhoea. The risk of skin rash and diarrhoea is greater with ticlopidine than with clopidogrel. Ticlopidine, but not clopidogrel, is associated with an excess of neutropenia and of thrombotic thrombocytopenic purpura.

Aspirin↗
PubMed2000

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.

BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. METHODS: We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.

Aspirin↗
PubMed1998

Investigating individual subjects and screening populations for asymptomatic carotid stenosis can be harmful.

OBJECTIVES: Trials suggesting that carotid endarterectomy in individual subjects with asymptomatic carotid stenosis reduces stroke risk have led to calls for screening. This study aimed to determine which groups might be harmed and which might benefit from a screening programme, and also to identify which individual subjects identified as positive for severe asymptomatic stenosis by carotid ultrasound are appropriate to put forward for further tests or procedures. METHODS: A probability model was used to estimate the outcomes of three screening strategies: carotid ultrasound followed by catheter angiography, or by magnetic resonance angiography (MRA), or ultrasound alone, followed by carotid endarterectomy if severe stenosis is detected. Information from the current literature was used to estimate sensitivity and specificity of ultrasound and MRA, risks of angiography and endarterectomy, and risk reduction after surgery for severe stenosis. For each strategy over a range of possible prevalences of severe asymptomatic stenosis, overall benefit to harm ratio was calculated, and number of strokes or deaths prevented or caused per 10,000 subjects screened. RESULTS: At the prevalence of carotid stenosis found in the general population (<1%) screening will cause more strokes than it prevents, even using the most optimistic published figures. Only at prevalences of over 20% are significant benefits seen, and then only in centres with high test sensitivity and specificity and very low angiographic and surgical risk. Groups with such a high prevalence have not yet been reliably identified. Screening individual subjects from high prevalence groups would have limited public health impact, with at best about 100 strokes prevented for every 10,000 screened at 20% prevalence. CONCLUSIONS: Investigating asymptomatic individual subjects for carotid stenosis may be harmful except in high prevalence groups. There is insufficient information about which these groups are, and at present screening cannot be recommended. Acting on a positive carotid ultrasound test in individual subjects

Adult↗
PubMed1997

Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration.

BACKGROUND AND PURPOSE: Comparing stroke rates in different parts of the world may increase our understanding of both etiology and prevention. However, comparisons are meaningful only if studies use standard definitions and methods, with comparably presented data. We compared the incidence of stroke and its pathological types (cerebral infarction, primary intracerebral hemorrhage, and subarachnoid hemorrhage) in recent studies from around the world. METHODS: Studies with a midyear of 1984 or later, fulfilling standard criteria for a comparable, community-based study, provided original data for comparative analyses. RESULTS: By mid-1995, data were available from 11 studies in Europe, Russia, Australasia, and the United States, comprising approximately 3.5 million person-years and 5575 incident strokes. Age- and sex-standardized annual incidence rates for subjects aged 45 to 84 years were similar (between approximately 300/100,000) and 500/100,000) in most places but were significantly lower in Dijon, France (238/100,000), and higher in Novosibirsk, Russia (627/100,000). In subjects aged 75 to 84 years, however, Novosibirsk no longer ranked higher than the other studies. The distribution of pathological types, when these were reliably distinguished, did not differ significantly between studies. CONCLUSIONS: The similarities in stroke incidence and pathological types are perhaps not surprising given that all the populations were westernized and mainly white. The higher rates in Novosibirsk, disappearing in the elderly, and the lower rates in Dijon have several potential explanations. These include methodological artifact and different patterns of population risk factors. Further work is needed to explore these possibilities and to extend our knowledge of stroke incidence to other parts of the world, especially developing countries.

Acute Disease↗
PubMed1996

Comparing stroke incidence worldwide: what makes studies comparable?

BACKGROUND: Comparing stroke rates in different parts of the world and at different points in time may increase our understanding of the disease. Comparisons are only meaningful if they are based on studies that use similar definitions, methods, and data presentation. SUMMARY OF REVIEW: We discuss the criteria that make such studies comparable, drawing on the experiences of recent studies performed around the world. If only those studies that fulfill the proposed criteria for comparison are considered, comparable data do not exist for vast areas of the world, including Africa, Asia, and South America. The importance of complete, community-based case ascertainment, including strokes managed outside the hospital, is emphasized. An approach for measuring and comparing the incidence of the pathological types of stroke (cerebral infarction, primary intracerebral hemorrhage, and subarachnoid hemorrhage) and subtypes of cerebral infarction is suggested. CONCLUSIONS: The "ideal" stroke incidence study does not exist, but studies closely approaching it will reveal the most reliable and comparable results. There is a need for further studies to fill the gaps in our knowledge of the worldwide incidence of stroke, particularly for developing countries.

Africa↗
PubMed1994

Laryngotracheal stenosis: a serious complication of percutaneous tracheostomy.

Tracheostomy in patients requiring prolonged artificial ventilation in intensive care is increasingly being performed by a percutaneous dilatational technique, in preference to the standard surgical method. Since its introduction numerous series have reported favourably on its general safety in the short-term, but there have been few reports of longer term follow-up of patients. We present four cases of laryngotracheal stenosis, a previously unreported complication associated with the technique, and discuss the relevance of these to the future practice of percutaneous tracheostomy.

Adult↗