Biomedical subjects

C Sudlow

Publications and source records attributed to C Sudlow.

10 recordsLinked to original sources

PubMed2004

Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to prophylactic doses of aspirin for the secondary prevention of occlusive vascular events. DATA SOURCES: Electronic databases. REVIEW METHODS: A total of 2906 titles and abstracts were rigorously screened and 441 studies were assessed in detail. Two RCTs were identified. For the assessment of cost-effectiveness, eight reviews were identified. The results were presented in structured tables and as a narrative summary. No additional clinical effectiveness data were presented in either of two company submissions. All economic evaluations (including accompanying models) included in the company submissions were assessed. Following this analysis, if the existing models (company or published) were not sufficient, a de novo model or modified versions of the models were developed. RESULTS: In the CAPRIE trial the point estimate for the primary outcome, i.e. ischaemic stroke, myocardial infarction (MI) or vascular death, favoured clopidogrel over aspirin, but the boundaries of the confidence intervals raise the possibility that clopidogrel is not more beneficial than aspirin. In terms of the secondary outcomes reported, there was a non-significant trend in favour of clopidogrel over aspirin but the boundaries of the confidence intervals on the relative risks all crossed unity. There was no difference in the number of patients ever reporting any bleeding disorder in the clopidogrel group compared with the aspirin group. The incidences of rash and diarrhoea were statistically significantly higher in the clopidogrel group than the aspirin group. Patients in the aspirin group had a higher incidence of indigestion/nausea/vomiting than patients in the clopidogrel group. Haematological adverse events were rare in both the clopidogrel and aspirin groups. No cases of thrombotic thrombocytopenic purpura were reported in either group. Treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2 compared with treatment with aspirin. ASA-MR-dipyridamole was significantly more effective than aspirin alone in patients with stroke or transient ischaemic attacks (TIAs) at reducing the outcome of stroke and marginally more effective at reducing stroke and/or death. Treatment with ASA-MR-dipyridamole did not statistically significantly reduce the risk of death compared to treatment with aspirin. The number of strokes was statistically significantly reduced in the ASA-MR-dipyridamole group compared with the MR-dipyridamole group. In terms of the other primary outcomes, stroke and/or death and death, the results favoured treatment with ASA-MR-dipyridamole but the findings were not statistically significant. There was no difference in the number of bleeding complications between the ASA-MR-dipyridamole and aspirin groups. The incidence of bleeding complications was significantly lower in the MR-dipyridamole treatment group. More patients in the MR-dipyridamole treatment groups experienced headaches compared to patients receiving treatment with aspirin alone. The York model assessed the cost-effectiveness of differing combinations of treatment strategies in four patient subgroups, under a number of different scenarios. The results of the model were sensitive to the assumptions made in the alternative scenarios, in particular the impact of therapy on non-vascular deaths. CONCLUSIONS: Clopidogrel was marginally more effective than aspirin at reducing the risk of ischaemic stroke, MI or vascular death in patients with atherosclerotic vascular disease, however, it did not statistically significantly reduce the risk of vascular death or death from any cause compared with aspirin. There was no statistically significant difference in the number of bleeding complications experienced in the clopidogrel and aspirin groups. MR-dipyridamole in combination with aspirin was superior to aspirin alone at reducing the risk of stroke and marginally more effective at reducing the risk of stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR-dipyridamole in combination with aspirin significantly reduced the risk of stroke. Treatment with MR-dipyridamole in combination with aspirin did not statistically significantly reduce the risk of death compared with aspirin. Compared with treatment with MR-dipyridamole alone, bleeding complications were statistically significantly higher in patients treated with aspirin and MR-dipyridamole in combination with aspirin. Due to the assumptions that have to be made, no conclusions could be drawn about the relative effectiveness of MR-dipyridamole, alone or in combination with aspirin, and clopidogrel from the adjusted indirect comparison. The following would apply for a cost of up to GBP20,000-40,000 per additional quality-adjusted life-year. For the stroke and TIA subgroups, ASA-MR-dipyridamole would be the most cost-effective therapy given a 2-year treatment duration as long as all patients were not left disabled by their initial (qualifying) stroke. For a lifetime treatment duration, ASA-MR-dipyridamole would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered and all patients were not left disabled by their initial stroke. In patients left disabled by their initial stroke, aspirin is the most cost-effective therapy. Clopidogrel and MR-dipyridamole alone would not be considered cost-effective under any scenario. For the MI and peripheral arterial disease subgroups, clopidogrel would be considered cost-effective for a treatment duration of 2 years. For a lifetime treatment duration, clopidogrel would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered. It is suggested that the combination of clopidogrel and aspirin should be evaluated for the secondary prevention of occlusive vascular events. Also randomised, direct comparisons of clopidogrel and MR-dipyridamole in combination with aspirin are required to inform the treatment of patients with a history of stroke and TIA, plus trials that compare treatment with clopidogrel and MR-dipyridamole for the secondary prevention of vascular events in patients who demonstrate a genuine intolerance to aspirin.

Aspirin↗

PubMed2004

Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation.

OBJECTIVES: To review systematically the clinical effectiveness and the cost-effectiveness of clopidogrel used in combination with standard therapy including aspirin, compared with standard therapy alone for the treatment of non-ST-segment elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases. Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous criteria. The quality of randomised controlled trials (RCTs) was assessed according to criteria based on NHS CRD Report No. 4, and the quality of systematic reviews was assessed according to the guidelines for the Database of Reviews of Effect (DARE) criteria. The quality of economic evaluations was assessed according to a specifically tailored checklist. The clinical effectiveness and cost-effectiveness of clopidogrel in combination with standard therapy compared with standard therapy alone were synthesised through a narrative review with full tabulation of the results of the included studies. In the economic evaluations, a cost-effectiveness model was constructed using the best available evidence to determine cost-effectiveness in a UK setting. RESULTS: One RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of high quality and showed that clopidogrel in addition to aspirin was significantly more effective than placebo plus aspirin in patients with non-ST-segment elevation ACS for the composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or stroke over the 9-month treatment period. However, clopidogrel was associated with a significantly higher number of episodes of both major and minor bleeding. The results from the five systematic reviews that assessed the adverse events associated with long-term aspirin use showed that aspirin was associated with a significantly higher incidence of haemorrhagic stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's submission was considered relevant from the perspective of the NHS. The review of this evidence highlighted potential limitations within the submission in its use of data and in the model structure used. These limitations led to the development of a new model with the aim of providing a more reliable estimate of the cost-effectiveness from the perspective of the UK NHS. This model indicated that clopidogrel appears cost-effective compared with standard care alone in patients with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per quality of life year (QALY). The results were most sensitive to the inclusion of additional strategies that assessed alternative treatment durations with clopidogrel. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in combination with aspirin was significantly more effective than placebo combined with aspirin in a wide range of patients with ACS. This benefit was largely related to a reduction in Q-wave myocardial infarction. There was no statistically significant benefit in relation to mortality. The trial data suggested that a substantial part of the benefit derived from clopidogrel is achieved by 3 months, with a further small benefit over the remaining 9 months of chronic treatment. The results from the base-case model suggest that treatment with clopidogrel as an adjunct to standard therapy (including aspirin) for 12 months, compared with standard therapy alone, is cost-effective in non-ST elevation ACS patients as long as the health service is willing to pay GBP6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a 'rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment.

Acute Disease↗

PubMed2002

Posture and fluids for preventing post-dural puncture headache.

BACKGROUND: Potentially disabling postural headache occurs after dural puncture in 1-70% of patients. It has been suggested that such headaches may be less common if patients routinely have a period of bed rest or receive supplementary fluids after the procedure. OBJECTIVES: To assess the effects on post dural puncture headache of a period of bed rest versus early mobilisation, of different positions during a period of bed rest, and of administering supplementary fluids after the procedure. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2000), MEDLINE (January 1994-December 1998), and EMBASE (January 1980-December 1998). We also searched the reference lists of articles identified electronically, and contacted trial authors for information about other potentially relevant studies. Date of the most recent search: December 2000. SELECTION CRITERIA: We sought randomised, unconfounded trials, among all types of patients, that compared the effects on post-dural puncture headache of: bed rest versus early mobilisation; head-down tilt versus horizontal or prone versus supine positions during bed rest; or the administration of supplementary fluids versus control. DATA COLLECTION AND ANALYSIS: One reviewer extracted data from the reports of all trials considered eligible for inclusion. The authors of included studies were invited to check the information extracted and provide any details that were unavailable in the published reports. Intention-to-treat analyses were performed. MAIN RESULTS: Eleven trials among 1723 patients compared either bed rest with immediate mobilisation or a longer versus a shorter period of bed rest. There was a non-significant relative increase in the odds of the primary outcome of postural headache among patients allocated more rather than less bed rest (196/639 [31%] bed rest versus 169/615 [27%] early mobilisation; odds ratio [OR] 1.21; 95% confidence interval [CI] 0.94 to 1.55). Analyses confined to the methodologically most rigorous trials gave similar results. Only two trials among 126 patients compared different positions during bed rest. No statistically significant differences were found, but small numbers made the comparisons imprecise. One trial among 100 patients assessed fluid supplementation. Again, the numbers of patients and outcome events were small, and indicated the possibility of both reduced and increased postural headache with additional fluids. REVIEWER'S CONCLUSIONS: There is no good evidence from randomised trials to suggest that routine bed rest after dural puncture is beneficial. The role of fluid supplementation in the prevention of post-dural puncture headache remains uncertain.

Bed Rest↗

PubMed2002

Epidural blood patching for preventing and treating post-dural puncture headache.

BACKGROUND: Dural puncture is a common procedure, but leakage of CSF from the resulting dural defect may cause postural headache after the procedure, and this can be disabling. Injecting an epidural blood patch around the site of the defect may stop this leakage, and so may have a role in preventing or treating post dural puncture headache. OBJECTIVES: To assess the possible benefits and harms of epidural blood patching in both the prevention and the treatment of post-dural puncture headache. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2000), MEDLINE (January 1994 to December 1998), and EMBASE (January 1980 to December 1998). We also searched the reference lists of relevant articles identified electronically, and asked both the authors of all included trials and colleagues with an interest in this area to let us know of any other potentially relevant studies not already identified. Date of last search: December 2000. SELECTION CRITERIA: We sought all properly randomised, unconfounded trials that compared epidural blood patch versus no epidural blood patch in the prevention or treatment of post-dural puncture headache among all types of patients undergoing dural puncture for any reason. The primary outcome of effectiveness was postural headache. DATA COLLECTION AND ANALYSIS: One reviewer extracted details of trial methodology and outcome data from the reports of all trials considered eligible for inclusion. We invited the authors of all such trials both to check the information extracted and to provide any details that were unavailable in the published reports. Intention-to-treat analyses were performed using the Peto O-E method. Information about adverse effects (post-dural puncture backache, epidural infection and lower limb paraesthesia) was also extracted. MAIN RESULTS: Three trials (77 patients) were eligible for inclusion. Methodological details were generally incomplete. Although the results of our analyses suggested that both prophylactic and therapeutic epidural blood patching may be of benefit, the very small numbers of patients and outcome events, as well as uncertainties about trial methodology, precluded reliable assessments of the potential benefits and harms of this intervention. REVIEWER'S CONCLUSIONS: Further, adequately powered, randomised trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache.

Blood Patch, Epidural↗

PubMed2001