New England Journal of Medicine November 07, 2026

Intensive Blood-Pressure Control in Patients with Previous Ischemic Stroke

Gisele Sampaio Silva, M. Julia Machline-Carrion, Karla Santo, et al.

Bottom Line

In patients with previous ischemic stroke or transient ischemic attack, targeting a systolic blood pressure of less than 120 mm Hg significantly reduced the risk of major cardiovascular events compared with targeting less than 140 mm Hg, though with a higher rate of renal adverse events.

Key Findings

1. Over a median follow-up of 3.9 years, the primary composite cardiovascular outcome occurred in 10.9% of the intensive-control group compared with 13.5% of the standard-control group (Hazard Ratio [HR] 0.79; 95% CI, 0.67 to 0.94).

2. The intensive-treatment strategy successfully lowered the mean systolic blood pressure to 122.0 mm Hg, compared with 135.2 mm Hg in the standard-treatment group.

3. Intensive blood-pressure lowering was associated with a higher incidence of a renal composite outcome (sustained 50% or greater decline in estimated glomerular filtration rate or progression to end-stage renal failure) and electrolyte disturbances compared to the standard group.

Study Design

Design

RCT

Open-Label

Sample

4,368

Patients

Duration

3.9 yr

Median

Setting

Multicenter, Brazil

Population Patients with elevated blood pressure and a clinically stable history of previous ischemic stroke or transient ischemic attack (TIA).

Intervention Intensive blood-pressure treatment targeting a systolic blood pressure of less than 120 mm Hg.

Comparator Standard blood-pressure treatment targeting a systolic blood pressure of less than 140 mm Hg.

Outcome A composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina or heart failure.

Study Limitations

• The open-label design could introduce performance or ascertainment bias, although clinical end points were adjudicated by an independent, blinded committee.

• The trial was conducted exclusively in Brazil (30 sites), which may limit the generalizability of the findings to different global healthcare settings and populations.

• Blinded aggregate reviews led to the downward revision of the target sample size (from an initially planned 7,000 to an actual enrollment of 4,368) and a lowered primary event threshold, marginally reducing the trial's statistical power.

• Patients with severe renal impairment were excluded from enrollment, limiting the extrapolation of these results to that high-risk demographic.

• The study evaluated clinically stable patients in a secondary prevention setting; the findings do not apply to blood pressure management during the acute phase of an ischemic stroke.

Clinical Significance

The OPTIMAL-STROKE trial provides definitive evidence that an intensive systolic blood pressure target (<120 mm Hg) is superior to a standard target (<140 mm Hg) for preventing recurrent cardiovascular events in stroke and TIA survivors. By demonstrating a 21% relative risk reduction in major cardiovascular outcomes, the study supports more aggressive secondary prevention targets in clinical practice. However, clinicians must carefully weigh this substantial cardiovascular benefit against the increased risk of renal decline and electrolyte disturbances, highlighting the necessity for careful patient selection and continuous monitoring of kidney function and electrolytes during treatment intensification.

Historical Context

The optimal blood pressure target for secondary stroke prevention has long remained controversial. While the landmark 2015 SPRINT trial conclusively established the cardiovascular benefits of a systolic target <120 mm Hg in high-risk patients, it specifically excluded individuals with a history of stroke. The 2013 SPS3 trial evaluated intensive blood pressure lowering in patients with recent lacunar strokes but failed to show a statistically significant reduction in its primary stroke outcome, largely because it was underpowered. As a result, subsequent international guidelines maintained relatively conservative secondary prevention targets (often <130 or <140 mm Hg). OPTIMAL-STROKE specifically addresses this critical evidence gap, confirming that the cardiovascular benefits of intensive blood pressure reduction extend to patients with a history of ischemic stroke or TIA.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

How does the physiology of cerebral autoregulation complicate blood pressure lowering in the acute versus chronic phase of an ischemic stroke?

Key Response

In the acute phase, the ischemic penumbra depends on systemic pressure due to impaired autoregulation, making intensive BP lowering dangerous. Chronically, autoregulation resets, and lower BP reduces shear stress and vascular remodeling, preventing recurrent events, though the kidneys may experience hypoperfusion as seen in the study.

Resident

When applying these findings in clinic, how should you manage a patient whose systolic BP reaches the <120 target but who develops a 30 percent increase in serum creatinine?

Key Response

The resident must recognize that a mild bump in creatinine (up to 30 percent) is often a hemodynamic effect of medications like ACE inhibitors or ARBs rather than true structural acute kidney injury. Management involves monitoring and continuing therapy if stable, while avoiding volume depletion, rather than immediately abandoning the intensive BP target.

Fellow

Does the mechanism of the index stroke (e.g., small vessel lipohyalinosis vs. severe intracranial atherosclerosis) alter the safety and efficacy of targeting a systolic BP under 120 mm Hg?

Key Response

Small vessel (lacunar) strokes typically benefit most from intensive BP lowering. Conversely, patients with severe flow-limiting large vessel intracranial stenosis depend on collateral perfusion, and intensive BP lowering could theoretically induce hemodynamic watershed infarctions, a critical subspecialty nuance when applying this trial.

Attending

How do we frame the competing risks of major cardiovascular events versus renal adverse events to patients when engaging in shared decision-making for intensive blood pressure control?

Key Response

Attendings must translate NNT and NNH into patient-centered outcomes. Preventing a disabling recurrent stroke often outweighs a reversible drop in eGFR or a non-oliguric AKI, but this requires personalized discussion about the patient baseline renal function, frailty, and values regarding dialysis versus stroke disability.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

What statistical models should be employed to account for the competing risk of mortality when evaluating the time-to-first major cardiovascular event in a predominantly elderly stroke cohort?

Key Response

Traditional Kaplan-Meier estimates can overestimate the incidence of the primary outcome in the presence of competing risks like non-cardiovascular death. Fine-Gray subdistribution hazard models or cause-specific hazard models are necessary to accurately estimate the true risk reduction attributable to intensive BP control.

Journal Editor

Given that intensive blood pressure trials are notoriously difficult to blind, how might performance bias and detection bias affect the reporting of renal adverse events?

Key Response

In an open-label or PROBE design, physicians aware of the intensive target may check basic metabolic panels more frequently or alter diuretic doses more aggressively, leading to a higher detection rate of asymptomatic AKI or laboratory abnormalities in the intensive arm compared to the standard arm.

Guideline Committee

Should the AHA/ASA secondary stroke prevention guidelines be updated from the current <130 mm Hg target to <120 mm Hg based on this trial, and what strength of recommendation should be applied?

Key Response

The committee must weigh the incremental cardiovascular benefit against the increased renal harm. Currently, AHA/ASA guidelines recommend <130 mm Hg (Class 1, Level A). Moving to <120 mm Hg might receive a Class 2a recommendation for highly selected patients without advanced CKD, emphasizing individualized therapy and rigorous monitoring, similar to the evolution of ACC/AHA general hypertension guidelines post-SPRINT.

Clinical Landscape

Noteworthy Related Trials

2001

PROGRESS Trial

n = 6,105 · Lancet

Tested

Perindopril-based blood pressure lowering regimen

Population

Patients with a history of stroke or transient ischemic attack

Comparator

Placebo

Endpoint

Fatal or non-fatal stroke

Key result: Active treatment reduced blood pressure by 9/4 mm Hg and reduced the risk of recurrent stroke by 28% compared to placebo.

2013

SPS3 Trial

n = 3,020 · Lancet

Tested

Intensive BP control (target systolic <130 mm Hg)

Population

Patients with recent symptomatic lacunar infarcts

Comparator

Standard BP control (target systolic 130-149 mm Hg)

Endpoint

Recurrent stroke

Key result: Intensive BP lowering did not significantly reduce the overall rate of recurrent stroke, but significantly reduced the rate of intracerebral hemorrhage.

2015

SPRINT Trial

n = 9,361 · NEJM

Tested

Intensive BP control (target systolic <120 mm Hg)

Population

Adults at high cardiovascular risk but without diabetes or prior stroke

Comparator

Standard BP control (target systolic <140 mm Hg)

Endpoint

Composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death

Key result: Intensive blood-pressure control resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

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