Abstract
The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed the benefits of blood pressure (BP) lowering for secondary stroke prevention in stroke survivors for the first time after a long dispute in the last century and triggered active hypertensive therapy for stroke patients globally in this century. A post hoc analysis of PROGRESS demonstrated that both the lowest risks of ischemic stroke and of hemorrhagic stroke were among the one-quarter of patients with the lowest achieved follow-up BP levels (median 112/72 mmHg), and that these risks increased progressively with higher follow-up BP levels in the large cohort of patients with previous stroke or transient ischemic attack. A similar tendency for an increased risk of ischemic/hemorrhagic stroke by higher follow-up BP levels was reproduced in subsequent stroke trials. Several trials sought to clarify the preventive effect against recurrent stroke by randomizing patients into two groups with different BP lowering targets. In patients with recent lacunar stroke in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, lowering systolic BP to < 130 mmHg significantly reduced the risk of intracerebral hemorrhage (ICH) by 63% and insignificantly reduced the risk of ischemic stroke by 16% compared to lowering to 130–149 mmHg. The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study, involving patients having a history of stroke within the previous 3 years showed similar results: lowering BP to < 120/80 mmHg, relative to < 140/90 mmHg, reduced the risk of ICH by 91% and that of ischemic stroke by only 9%. These trials failed to demonstrate a significant reduction in the risk of any stroke as the primary outcome by intensive BP lowering, since the incidence of ischemic stroke was much higher than that of ICH for both trials. A meta-analysis of these two trials and two more small studies finally succeeded in showing a statistically significant 22% reduced risk for any stroke recurrence by lowering systolic BP to at least < 130 mmHg. The current guidelines recommend systolic BP control aiming at < 130 mmHg or 120–130 mmHg for adults who experience ischemic stroke. RESPECT is epochal as the first large population trial to examine the importance of systolic BP lowering to < 120 mmHg. Such strict control would undoubtedly decrease incidental ICH, especially for patients taking antithrombotic agents. However, the necessity of strict BP control for protection of brain tissues from ischemic injury is still an unresolved matter that needs to be addressed in future studies.
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