Showing papers by "Bruce Neal published in 2001"

Study rationale and design of ADVANCE: Action in diabetes and vascular disease - Preterax and diamicron MR controlled evaluation

Abstract: AIMS/HYPOTHESIS: Patients with Type II (non-insulin-dependent) diabetes mellitus are at increased risk of macrovascular and microvascular disease, both of which are reduced by controlling raised blood pressure in hypertensive patients. Intensive glycaemic control has also been shown to reduce microvascular disease but the effects on macrovascular disease remain uncertain. This study will examine the hypotheses that lowering blood pressure with an ACE inhibitor-diuretic combination and intensively controlling gylcaemia with a sulphonylurea-based regimen in high-risk patients with Type II diabetes (both hypertensive and non-hypertensive) reduces the incidence of macrovascular and microvascular disease. METHODS: The study is a 2 x 2 factorial randomised controlled trial that will include 10000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomised to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regimen or usual guidelines-based therapy. Primary outcomes are, first, the composite of nonfatal stroke, non-fatal myocardial infarction or cardiovascular death and, second, the composite of new or worsening nephropathy or diabetic eye disease. The scheduled average duration of treatment and follow-up is 4.5 years. The study will be conducted in approximately 200 centres in Australasia, Asia, Europe and North America. CONCLUSION/INTERPRETATION: ADVANCE is designed to provide reliable evidence on the balance of benefits and risks conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.

Blood pressure lowering in diabetes: a brief review of the current evidence and description of a new trial.

Abstract: 1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.

Prospectively designed overviews of recent trials comparing antihypertensive regimens based on different drug classes.

Abstract: Randomized trials have provided clear evidence of the beneficial effects of many different blood pressure-lowering regimens compared with placebo. The comparative effects of antihypertensive regimens based on different drug classes are less well established. The Blood Pressure Lowering Treatment Trialists’ Collaboration conducted a series of prospectively designed overviews of randomized trials that compared the effects of different drug classes on major cause-specific outcomes. These overviews found no differences between the effects of regimens based on angiotensin converting enzyme inhibitors and those based on diuretics or b-blockers. There was limited evidence of small differences between regimens based on calcium antagonists and those based on diuretics or s-blockers. The overviews of regimens based on calcium antagonists compared with those based on angiotensin converting enzyme inhibitors recorded too few events to provide reliable findings. Over the next few years, the findings of ongoing trials and future cycles of overview analyses conducted by the Collaboration should substantially add to these data.

ACE inhibitor-based blood pressure lowering - first line therapy among individuals with hypertension?

Abstract: INTRODUCTION By the mid 1990's, systematic overviews (meta-analyses) of unconfounded randomised controlled trials of blood pressure lowering had demonstrated that reductions in blood pressure of about 10-12 mmHg systolic and 5-6 mmHg diastolic conferred relative reductions in stroke risk of about 38% and in coronary heart disease risk of about 16% [1-3]. The sizes of these effects were broadly consistent with those anticipated from observational studies of the long-term associations of blood pressure with stroke and coronary heart disease risk [4-6]. However, the trials included in these overviews were of blood pressurelowering regimens based mainly on diuretics and beta-blockers. Since large-scale randomised trials of the effects of ACE inhibitors compared to placebo among hypertensive patients had not been completed, the overviews provided no direct evidence about their effects. At the time, evidence about the effects of ACE inhibitors on major cardiovascular outcomes was restricted to indirect data from two randomised controlled trials that compared the effects of ACE inhibitor-based regimens with diureticor beta-blockerbased regimens [7, 8]. These two trials identified no differences in the effects of the regimens on stroke or coronary heart disease risk but even in combination were too small to exclude anything but very large differences. Evidence about the clinical effects of ACE inhibitors in hypertensive patients was therefore largely restricted to information about intermediate outcomes such as blood pressure [7, 8] and surrogate endpoints such as renal function [9, 10] and left ventricular hypertrophy [11], although clear benefits had been demonstrated on major cardiovascular outcomes in patients with heart failure [12] and acute myocardial infarction [13].