Lower target blood pressures are safe and effective for the prevention of recurrent stroke: The PROGRESS trial

Objective: To explore the likely optimum blood pressure (BP) level for patients with a history of cerebrovascular disease. Methods: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in 6105 patients with cerebrovascular disease. The present study comprises two series of post hoc analyses. The first was designed to investigate the effects of randomized treatment on recurrent stroke by baseline BP levels, and the second was a corresponding observational analysis investigating the association between achieved follow-up BP levels and recurrent stroke risk. Results: Analyses of the randomized treatment comparisons showed that BP lowering with combination therapy produced similar risk reductions in each of four subgroups defined by baseline BP of less than 120, 120-139, 140-159, and 160 mmHg or greater (P homogeneity = 0.5). The effects of single-drug therapy were also comparable across these subgroups (P homogeneity = 0.2), but consistently greater benefits were observed with combination compared to single-drug therapy. The analyses of achieved follow-up BP showed that the lowest risk of recurrence was among the one-quarter of participants with the lowest follow-up BP levels (median 112/72 mmHg), and that risks rose progressively with higher follow-up BP levels. Minor side-effects were progressively more common at lower BP levels (P homogeneity = 0.04), but there was no excess of serious complications (all P homogeneity > 0.2). Conclusion: These analyses provide no evidence of a J-curve relationship between BP level and stroke risk among patients with cerebrovascular disease, and identify no patient group among whom more intensive BP lowering would not be expected to produce greater risk reductions.