Showing papers by "Clinical Trial Service Unit published in 1994"

Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease

Abstract: Most evidence about the effects of blood pressure on the risks of cardiovascular disease derives from two principal sources: prospective non-randomised observational studies of the associations between blood pressure and the incidence of stroke and of coronary heart disease, and randomised trials of antihypertensive drug therapy. The focus of the first part of this chapter concerns the evidence from observational studies, which--despite the possibility of confounding by other risk factors--may be more relevant to the eventual effects of prolonged blood pressure differences on stroke and coronary heart disease risk. The focus of the second part concerns the evidence from randomised trials of antihypertensive drug treatment, which are more relevant to assessing how rapidly, and to what extent, the epidemiologically expected reductions in stroke or in coronary heart disease are produced by suddenly lowering blood pressure in middle and old age.

Obtaining data from randomised controlled trials : how much do we need for reliable and informative meta-analyses ?

Abstract: Many randomised controlled trials compare treatments that will produce only moderate differences in outcome, but these differences can be clinically important. However, they are difficult to assess reliably and require a large amount of randomised evidence. This can be achieved through large prospective randomised trials which will accrue future patients, the meta-analysis of results from randomised trials involving patients from the past, or--ideally--both. The techniques require that all possible biases are minimised, and in meta-analyses this can best be achieved by ensuring that all of the randomised evidence--both trials and participants in those trials--is included. The meta-analysis of individual patient data has been described as the gold standard for this approach. It will remove many of the problems associated with relying solely on published data and some of the problems arising from a reliance on aggregate data, and will also add to the analyses that can be performed. Such projects, however, require considerable time and effort.

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study

Abstract: We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Autografting for patients with CML in chronic phase: an update. Hammersmith BMT Team LRF Centre for Adult Leukaemia.

Abstract: Between 1984 and 1992, 21 patients with chronic myeloid leukaemia (CML) in chronic phase (CP) were treated with high-dose chemotherapy (or chemoradiotherapy) followed by autografting with unmanipulated peripheral blood stem cells (PBSC). 12 of these patients survive at a median of 82 months from the time of autografting (range 9-105 months). Nine patients died, six of leukaemia in transformation and three from other causes. Survival of these 21 autograft patients was compared to that of 636 age-matched controls on the Medical Research Council's (MRC) data base, who had been treated with conventional chemotherapy over the same period. Autografted patients had a significantly longer survival at 5 years post autograft than chemotherapy patients (56% v 28%) even after appropriate allowance for time at risk before autograft (Mantel-Byar, 2P = 0.003). There was no difference in survival whether autografting was performed early in the disease or later or whether the PBSC had been harvested soon after diagnosis or later. If the benefits of autografting in chronic phase seen in this non-randomized series can be confirmed in a randomized study, autografting might be the treatment of choice for younger CML patients who do not have suitable donors for allogeneic transplant.

Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials. Antiplatelet Trialists' Collaboration.

Abstract: Venous thromboses and pulmonary embolism remain an important cause of morbidity and mortality both in surgical patients and in immobilised medical patients.*RF 1-5* Various thromboprophylactic treatments have, therefore, been devised to prevent or limit thromboembolism. Our previous systematic overview (or meta-analysis) of randomised trials of perioperative subcutaneous heparin found that among surgical patients such treatment can roughly halve the risk not only of deep venous thrombosis but, more importantly, of pulmonary embolism6 (see fig 1). Subcutaneous heparin is now widely recommended for surgical or medical patients at high risk of venous occlusion.*RF 3-5* The recent Antiplatelet Trialists' Collaboration overview of the thromboprophylactic effects of antiplatelet therapy used prospectively determined criteria for trial inclusion and treatment comparisons that were similar to those of the previous heparin overview.*RF 6-8* The aim was to include all unconfounded properly randomised trials of antiplatelet versus no antiplatelet therapy (or of one antiplatelet regimen versus another) that could have been available for review by March 1990 in which deep venous thrombosis was systematically and unbiasedly monitored. (Parts I and III of the previous overview report give a fuller description of the methods used.1,7 The appropriateness of using “assumption free” statistical methods rather than the “random effects” model when combining trial results, as when combining results from different centres in a multicentre trial, has been discussed in detail previously.9,10) Such randomised trials were to be included whether or not the treatment comparison was “blinded” by placebo control. This was also the case in the heparin overview, where exclusion of informative “open” trials (in particular, the important open international multicentre trials coordinated by Professor V V Kakkar11) would have been equally inappropriate. Analyses confined to placebo controlled studies, which may be less subject to treatment dependent biases in the assessment …