Blood pressure lowering for the secondary prevention of stroke: Rationale and design for PROGRESS
Background. Usual blood pressure levels have been shown to be directly and continuously associated with the risks of initial and recurrent stroke. Blood pressure lowering has been demonstrated to reduce the risk of a first stroke in hypertensive patients, but there is uncertainty about the effects of reducing blood pressure in patients with a history of cerebrovascular disease, for whom stroke risks are particularly high. The primary objective of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) is to determine the effects of blood pressure reduction on stroke risk in patients with a history of cerebrovascular disease. Design and treatment. PROGRESS is a randomized, double-blind, placebo-controlled clinical trial of an angiotensin converting enzyme (ACE) inhibitor-based blood pressure lowering treatment regimen. Before randomization, there is a 4-week run-in phase on open-label treatment, after which patients are assigned to continued treatment or to placebo. Following randomization, the trial treatments comprise perindopril (4 mg daily) plus indapamide (2.5 mg daily) or matching placebos for patients without an indication for or contraindication to treatment with a diuretic, and perindopril alone or matching placebo for all other patients. The scheduled duration of treatment and follow-up is a minimum of 4 years. Patients. The study will involve 6000 patients with a proven transient ischaemic attack (including amaurosis fugax) or stroke (cerebral infarct, cerebral haemorrhage or stroke of unknown type) in the past 5 years. The patients selected will have no known definite indication for or contraindication to treatment with an ACE inhibitor and no disability likely to prevent regular attendance at study clinics. Patients will be recruited from collaborating clinical centres in Australia, Belgium, China, France, Italy, Japan, New Zealand, Sweden and the United Kingdom. Major outcomes. Stroke is the primary study outcome, and secondary outcomes include fatal or disabling strokes, total major cardiovascular events, cardiovascular deaths and dementia.