The PROGRESS study: rationale and design

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.