PROGRESS: Prevention of Recurrent Stroke

Abstract

The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized placebo-controlled trial which clearly demonstrated that perindopril-based blood pressure (BP)-lowering treatment is one of the most effective and generalizable strategies for secondary prevention of stroke. Beneficial effects of BP lowering were observed on recurrent stroke, other cardiovascular events, disability, dependency, and cognitive function across a variety of subgroups defined by age, sex, geographical region, body mass index, diabetes, atrial fibrillation, chronic kidney disease, and baseline BP levels. Once patients with stroke have stabilized, all patients should receive BP-lowering therapy irrespective of their BP levels. On the basis of recommendations from current international guidelines, BP should be lowered to <140/90 mm Hg in all patients with cerebrovascular disease and to <130/80 mm Hg if therapy is well tolerated.

Figure 1

Cumulative incidence of stroke (A) and major coronary events (B) among participants assigned active treatment and those assigned to placebo. Reproduced with permission from Elsevier and Oxford University Press. ⁹ , ¹³

Figure 2

Effects of blood pressure–lowering on serious clinical outcomes. Solid boxes represent estimates of relative risk of outcomes (hazard ratio for stroke, major coronary events, heart failure, major vascular events, vascular death and total death, and odds ratio for disability and dependency). Unfilled boxes represent subtypes of disability and dependency; areas of the boxes are proportional to the inverse variance of the estimates. Vertical lines represent 95% confidence intervals (CIs). Adapted from previously published figures with permission from Elsevier, Oxford University Press and Wolters Kluwer Health. ⁹ , ¹³ , ¹⁴

Figure 3

Effects of blood pressure–lowering on different types of stroke. CI indicates confidence interval; ICH, intracerebral hemorrhage; CAA, cerebral amyloid angiopathy; HT, hypertension. Solid boxes represent estimates of hazard ratio of total ischemic stroke, ICH, stroke of unknown type, and total stroke. Unfilled boxes represent subtypes of ischemic stroke and ICH. Adapted from previously published figures with permission from Wolters Kluwer Health. ⁶ , ¹⁷

Figure 4

Effects of blood pressure–lowering on dementia and cognitive decline. Combination therapy indicates perindopril plus indapamide, while single‐drug therapy indicates perindopril alone. Solid boxes represent estimates of odds ratio of dementia and cognitive decline. Unfilled boxes represent effects on subtypes of dementia and cognitive decline or effects in subgroups. CI indicates confidence interval. Adapted from previously published figures with permission from the American Medical Association. ²⁰

Figure 5

Effects of blood pressure–lowering on stroke among major clinical subgroups. CI indicates confidence interval; ANZ, Australia and New Zealand; BMI, body mass index; GFR, glomerular filtration rate. Solid boxes represent estimates of hazard ratio of stroke. Adapted from previously published figures with permission from Wolters Kluwer Health, Taylor & Francis A B and American Society of Nephrology. ²³ , ²⁸

Figure 6

Annual rates of ischemic stroke and intracerebral hemorrhage according to achieved follow‐up systolic blood pressure levels. Annual incidence rates and P values were controlled for age, sex, smoking, diabetes, study treatment, and combination therapy. Solid boxes represent estimates of annual incidence rates of stroke. Centers of the boxes are placed at the estimates of annual incidence rates and at median values of systolic blood pressure. Areas of the boxes are proportional to the number of events. Vertical lines represent 95% confidence intervals. P trend =.0005 for ischemic stroke, <.0001 for intracerebral hemorrhage. Reproduced with permission from Wolters Kluwer Health. ³³

Figure 7

Effects of blood pressure–lowering with combination therapy of perindopril plus indapamide on stroke by baseline blood pressure. Solid boxes represent estimates of hazard ratio of stroke. CI indicates confidence interval. Adapted from previously published figures with permission from Wolters Kluwer Health. ³³

Figure 8

Meta‐analysis of 16 randomized controlled trials of blood pressure lowering for secondary prevention of stroke. ⁹ , ¹¹ , ¹² , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁶ Solid boxes represent estimates of trials. Diamonds represent estimates and 95% confidence intervals (CIs) for overall effects. Overall estimates of effect and 95% CI were calculated using random‐effects models and inverse variance weighting. See text for trial name expansions.

Figure 9

Meta‐regression analysis of 9 randomized controlled trials of blood pressure lowering ⁹ , ¹¹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁶ to investigate association of reduction in systolic blood pressure with risk reduction for recurrent stroke. Nine randomized controlled trials for secondary prevention of stroke published after 1990 with information on reduction in systolic blood pressure were included. The area of each circle is proportional to inverse variance of log relative risk. The fitted line represents summary meta‐regressions for recurrent stroke. CI indicates confidence interval.