Blood Pressure Management for Stroke Patients Beyond the JSH 2025 Guidelines
核心洞察
The JSH 2025 guidelines establish a universal office blood pressure target of <130/80 mmHg across populations, including chronic stroke (搜索) patients, with a stricter <120/80 mmHg target for those at high risk of recurrent intracerebral hemorrhage (搜索).
Intensive systolic blood pressure control to <130 mmHg significantly reduces recurrent stroke (搜索) and major cardiovascular events, driven primarily by a reduction in hemorrhagic rather than ischemic stroke (搜索).
Acute-phase blood pressure targets remain unsettled, with prehospital lowering benefiting hemorrhagic stroke (搜索) patients but potentially harming those later diagnosed with ischemic stroke (搜索).
The Japanese Society of Hypertension (搜索) (JSH) 2025 guidelines introduce a universal office blood pressure (BP) target of <130/80 mmHg across populations, including patients with chronic stroke (搜索). This represents a significant evolution from earlier guidance, which had maintained a target of <140/90 mmHg until the JSH 2014 guidelines. For patients with chronic ischemic stroke (搜索) who have severe bilateral carotid artery stenosis, occlusion of the main cerebral artery, or unassessed vessels, treatment should proceed on an individual basis, while patients with chronic intracerebral hemorrhage (搜索) (ICH) at high risk of recurrence should lower BP to <120/80 mmHg.
Evolution of Target Blood Pressure for Chronic Stroke
The path to the current <130/80 mmHg target has taken roughly two decades. A subanalysis of the Perindopril Protection Against Recurrent Stroke (搜索) Study (PROGRESS) showed that the risk of stroke recurrence declined as mean systolic blood pressure (SBP) during follow-up fell to around 120 mmHg, leading to the adoption of a pragmatic threshold of approximately 140 mmHg. The JSH 2019 guidelines first proposed a target of <130/80 mmHg for chronic ischemic stroke (搜索) patients, citing the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and the prospective observational Bleeding with Antithrombotic Therapy (BAT) Study.
In SPS3, lacunar stroke (搜索) patients were randomly assigned to SBP-control targets of 130–149 mmHg or <130 mmHg. After a mean follow-up of 3.7 years, lowering SBP below 130 mmHg significantly reduced the risk of ICH, although the risk of any stroke was not significantly reduced. In the BAT Study, the optimal cutoff BP level to predict impending risk of intracranial hemorrhage was ≥130/81 mmHg using receiver operating characteristic curve analysis.
Evidence Supporting Intensive Blood Pressure Control
The Recurrent Stroke (搜索) Prevention Clinical Outcome (RESPECT) Study from Japan randomized 1,263 patients with a history of stroke 1:1 to BP control of <140/90 mmHg or <120/80 mmHg. The annualized rate of recurrent stroke (2.26% vs. 1.65%) was not statistically significant between groups, whereas the rate of ICH (0.46% vs. 0.04%) was reduced in the intensive treatment group (hazard ratio 0.09, 95% confidence interval 0.01–0.70).
When this finding was pooled with three previous randomized controlled trials targeting SBP <125 mmHg or <130 mmHg, the risk ratio favored intensive BP control (relative risk 0.78, 95% confidence interval 0.64–0.96). An updated meta-analysis integrating seven trials demonstrated significant reductions in recurrent stroke (搜索) and major cardiovascular events in the intensive BP control arm targeting SBP <130 mmHg or lower.
Notably, while intensive BP lowering suppressed the onset of ICH (or hemorrhagic stroke (搜索)) across SPS3, PROGRESS, and the meta-analysis, it did not significantly prevent the occurrence of ischemic stroke (搜索). In the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial, the recurrent stroke rate was insignificantly higher in patients with follow-up SBP of 120–129 mmHg (7.2%) and significantly higher in those with levels <120 mmHg compared to those at 130–139 mmHg. This rebounding, termed the J-curve phenomenon, appears relatively often in patients with large artery atherosclerosis with steno-occlusion of major cerebral arteries.
Antihypertensive Agent Selection
In the JSH 2014 and 2019 guidelines, calcium channel blockers, renin-angiotensin system inhibitors (angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors), and low-dose thiazide diuretics were the major antihypertensive agents for stroke (搜索) patients. β-blockers do not appear suitable for stroke patients. JSH 2025 describes two new second-choice drugs in greater detail: angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists.
An angiotensin receptor-neprilysin inhibitor is a 1:1 monocomplex of sacubitril, a prodrug of sacubitrilat, and valsartan. Sacubitrilat increases endogenous natriuretic peptides by inhibiting neprilysin, producing a dual antihypertensive effect through activation of endogenous natriuretic peptide function and angiotensin II receptor type 1 blockade. Mineralocorticoid receptor antagonists suppress urinary potassium excretion and promote sodium excretion. Both agents are promising, but evidence for their antihypertensive effects remains insufficient, partly because their use is largely confined to Japan with limited global adoption.
Resistant Hypertension and Renal Denervation
Resistant hypertension is defined as uncontrolled high BP despite adequate lifestyle changes and maximal antihypertensive drug therapy, including maximum tolerated dosages of three or more agents from different classes including a diuretic. Its prevalence ranges from 9% to 40% in adults with treated hypertension. In the nationwide Japan Morning-Surge Home BP (J-HOP) study, patients with resistant hypertension had a hazard ratio of total cardiovascular disease risk of 2.02 (95% confidence interval 1.38–2.94) compared to those with controlled BP using fewer than three classes of antihypertensive agents.
Patients with resistant hypertension are eligible for renal denervation, which removes the afferent and efferent nerve systems of the renal artery to prevent sympathetic activation and stabilize BP. Randomized controlled trials comparing renal denervation with sham operation showed both efficacy in lowering BP over the entire 24-hour period and safety. The therapy has now been covered by Japan's national health insurance system.
Acute-Phase Blood Pressure Management
Recommendations for acute-phase stroke (搜索) remain unsettled. The BP target for ischemic stroke (搜索) patients receiving intravenous thrombolysis is <180/105 mmHg, a threshold derived from protocols of previous randomized controlled trials rather than their results. The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) compared a lower SBP target of 130–140 mmHg over 72 hours to the standard target and showed a safer outcome, but functional status at 90 days did not differ between groups.
For patients undergoing mechanical thrombectomy, the JSH 2025-recommended SBP target is <180 mmHg. A meta-analysis published after JSH 2025 based on six randomized controlled trials found that intensive BP control to <140 mmHg or lower was associated with lower rates of good functional outcome, indicating 140–180 mmHg as an optimal level.
For ischemic stroke (搜索) patients without reperfusion therapy, guidelines uniformly recommend withholding BP lowering unless BP is ≥220/120 mmHg. BP lowering initiated within 48–72 hours after stroke (搜索) onset was proven safe but did not improve functional outcomes in several randomized controlled trials.
For acute ICH patients, the SBP target is <140 mmHg in several guidelines, including JSH 2025, mainly based on the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2). INTERACT2 was a marginally positive trial, with a modest difference in the proportion of death or major disability at 90 days between intensive (<140 mmHg, 52.0%) and standard (<180 mmHg, 55.6%) SBP lowering.
In the INTERACT4 trial, patients with suspected stroke (搜索) within 2 hours of onset were randomized to prehospital SBP lowering to 130–140 mmHg or usual BP management. A poor functional outcome was less common after prehospital BP lowering (common odds ratio 0.75, 95% confidence interval 0.60–0.92) in patients later diagnosed with hemorrhagic stroke. However, in participants later diagnosed with ischemic stroke (搜索), a poor functional outcome was more common after prehospital BP lowering (common odds ratio 1.30, 95% confidence interval 1.06–1.60). The shorter the time from onset, the greater the apparent benefit of intensive BP lowering on outcomes in hemorrhagic stroke.
Future Directions
Advances in hyperacute treatments for ischemic stroke (搜索) are likely to influence BP management strategies. If intravenous thrombolysis or mechanical thrombectomy can achieve sufficient reperfusion, including at the microcirculation level, the risk of aggravating ischemia due to BP reduction may be reduced, potentially enabling more aggressive BP lowering. For ICH patients, how quickly BP lowering is initiated appears critical to treatment success. While prehospital diagnosis of ICH is already possible in some regions using CT-equipped ambulances (mobile stroke (搜索) units), the development of technologies such as blood-based biomarkers that can accurately diagnose ICH is anticipated to allow a broader population of patients to benefit.