Showing papers by "Bruce Neal published in 1995"

The PROGRESS study: Rationale and design

Abstract: Rationale : Patients with a history of cerebrovascular disease have a very high risk of stroke, and usual levels of both systolic and diastolic blood pressure are directly and continuously associated with this risk. Trials of blood pressure lowering in patients with transient ischaemic attacks or stroke have been too small to reliably detect the effects on stroke risk of the modest blood pressure reductions achieved. Objectives : The primary objective of PROGRESS is to determine precisely the effects of blood pressure reduction with an angiotensin converting enzyme (ACE) inhibitor-based regimen on the stroke risk in patients with a history of transient ischaemic attacks or minor stroke. Design : The study is a randomized, double-blind, placebo-controlled clinical trial. Before randomization, there is a 4-week run-in phase on open-label ACE inhibitor treatment. The scheduled duration of treatment and follow-up is 4-5 years. Setting : The study will be conducted in collaborating clinical centres in Australia, Belgium, the People's Republic of China, France, Italy, Japan, New Zealand, Sweden and the United Kingdom. Patients : The study will involve 6000 patients with a history of transient ischaemic attacks or stroke (ischaemic or haemorrhagic) in the past 5 years. To be eligible patients should have no definite indication for or contra-indication to treatment with an ACE inhibitor and no disability likely to prevent regular attendance at study clinics. Interventions : Study treatment will comprise perindopril and indapamide or matching placebos for patients without an indication for or contra-indication to treatment with a diuretic, perindopril alone or matching placebo for all other patients. Study outcomes : The primary study outcome is total strokes and secondary outcomes include fatal or disabling strokes, total major cardiovascular events, cardiovascular deaths, cognitive function and dementia, and disability and dependency.

Blood pressure lowering for the primary and secondary prevention of coronary and cerebrovascular disease.

Abstract: An overview of the 17 completed randomised trials of antihypertensive treatment demonstrates that a 5-6 mm Hg reduction in DBP reduced stroke risk by 38% (SD 4) and CHD risk by 16% (SD 4). These results indicate that a few years' treatment with diuretic- or beta-blocker-based therapy produces most or all of the long-term stroke avoidance and much of the long-term CHD avoidance that would be predicted from observational epidemiological studies, given the blood pressure reductions that were achieved in the trials. The relative risk reductions were similar in trials of older and younger patients, although the absolute reduction in events was more than twice as great in the trials in older patients. From these results it can be estimated that in fully compliant patients at similar risk of vascular disease to those included in the trials, antihypertensive treatment for 5 years would prevent one major vascular event among every 20 older patients and one major vascular event among every 60 younger patients. Obviously the benefits of treatment will be greater among those at higher risk than the patients included in the previous trials. The greatest benefits are likely to be achieved in those with a history of vascular disease since their risk of future events is particularly high. Among such patients it is possible that blood pressure reduction will confer worthwhile benefits in those without hypertension, as well as those with hypertension. It is also possible that the benefits of treatment will be determined by the size of the blood pressure reduction and by the choice of the anti-hypertensive agent. However, each of these possibilities requires confirmation in large scale randomised controlled trials.