Intensive blood pressure lowering for ischemic stroke patients: does it prevent ischemia or bleeding?

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 [ 1 ] 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 [ 2 ]. A similar tendency for an increased risk of ischemic/hemorrhagic stroke by increased follow-up BP levels was reproduced in subsequent stroke trials (Fig. 1 ) [ 3 ]. 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 [ 4 ]. 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% [ 5 ]. 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 [ 5 ]. Fig. 1 The risk of incident stroke by mean systolic blood pressure quartiles in the PRASTRO-1 trial. A total of 3747 patients with noncardioembolic ischemic stroke randomly assigned (1:1) to receive prasugrel or clopidogrel are divided into quartiles according to mean follow-up systolic blood pressure levels (Q1: ≤ 126.1 mmHg, Q2: 126.1–132.5 mmHg, Q3: 132.5–138.6 mmHg, Q4: > 138.6 mmHg). The risks of any, ischemic, and hemorrhagic strokes by quartiles during the median follow-up of 1.8 years are shown. The markers represent the hazard ratios relative to Q1. The bars show the 95% confidence intervals. Logarithmic scales are used for the y -axes. Edited based on data of Ref. [ 3 ] Full size image