For years, the most important blood-pressure trial in medicine had a major gap: people who had already survived a stroke were left out. In 2015, the Systolic Blood Pressure Intervention Trial, or SPRINT, showed that lowering systolic blood pressure below 120 mm Hg reduced cardiovascular events in high-risk adults and changed treatment guidelines. But because SPRINT excluded patients with a history of stroke or transient ischemic attack, it did not answer the question that mattered most for stroke survivors.
Smaller studies in this group, including RESPECT in Japan and SPS3 in North America, offered clues but not a definitive answer. For the estimated 185,000 Americans who suffer a recurrent stroke each year, the best blood-pressure target after a first stroke had remained uncertain for more than a decade.
That uncertainty has now been addressed by a landmark result.
The OPTIMAL-Stroke trial, presented by principal investigator Gisele Sampaio, MD, PhD, of the Federal University of São Paulo and Hospital Israelita Albert Einstein, enrolled 4,368 adults with a previous ischemic stroke or transient ischemic attack at 30 health centers in Brazil. It is the largest randomized controlled trial ever conducted specifically in this population. After an average follow-up of 3.9 years, patients assigned to intensive blood-pressure treatment with a systolic goal below 120 mm Hg did better on every major outcome than those treated to the standard goal of below 140 mm Hg.
What the Trial Showed
The primary endpoint, a composite of major adverse cardiovascular events including cardiovascular death, heart attack, any stroke, and hospitalization for unstable angina or heart failure, occurred in 10.9% of patients in the intensive group and 13.5% in the standard group. That amounts to about a 21% reduction in major cardiovascular events.
The result most relevant to stroke survivors was the recurrence rate: recurrent stroke occurred in 4.7% of patients receiving intensive treatment versus 6.4% in the standard-treatment group, a relative reduction of about 27%. The 27% figure applies to repeat stroke specifically, while the 21% figure refers to the broader cardiovascular composite. Both point in the same direction and are clinically meaningful.
"High blood pressure is the single most important modifiable risk factor for stroke," Sampaio said in a statement. "These results confirm that for patients who have already had a stroke, treating aggressively is not just an option — it's the evidence-based path."
Otávio Berwanger, MD, PhD, chair of the steering committee and affiliated with the George Institute for Global Health and Imperial College London, said controlling blood pressure after a stroke is especially important because it can help prevent another stroke.
Why This Trial Matters
To appreciate the importance of OPTIMAL-Stroke, it helps to revisit SPRINT. That study enrolled 9,361 adults at high cardiovascular risk, mostly older patients without diabetes or prior stroke. The intensive arm reached an average systolic blood pressure of about 121 mm Hg, compared with about 134 mm Hg in the standard arm. The intensive strategy led to fewer major cardiovascular events and lower all-cause mortality, and it helped reshape the 2017 ACC/AHA hypertension guidelines.
Those guidelines, and a later hypertension update, extended the evidence to the broader hypertensive population. Meanwhile, the 2021 AHA/ASA secondary stroke prevention guideline recommended a target below 130/80 mm Hg for most stroke survivors. That was more aggressive than the old below-140 standard, but still higher than the intensive target used in SPRINT. The more recent hypertension guidance also supports targets below 120 mm Hg when tolerated, but that recommendation was still based on extrapolation rather than direct evidence in stroke survivors.
OPTIMAL-Stroke fills that gap. Participants entered the study with a mean systolic blood pressure of 146.7 mm Hg, a level typical of many stroke survivors seen in routine care. The average age was 64 years, and 47.9% of participants were women.
The Biology Behind the Benefit
Lowering blood pressure helps prevent stroke through several pathways. It reduces stress on blood vessel walls, slowing plaque formation and instability, which are central to many ischemic strokes. It also reduces strain on the left ventricle, lowering the risk of atrial fibrillation, a major cause of embolic stroke. In the brain's small vessels, sustained blood-pressure control slows the damage that can lead to white matter disease, lacunar infarcts, cognitive decline, and recurrent stroke.
There is an important difference between the acute and chronic settings. In the first hours after an ischemic stroke, the brain's ability to regulate blood flow, known as cerebral autoregulation, is impaired. Normally, blood vessels adjust their diameter to keep cerebral blood flow stable when systemic pressure changes. After an acute ischemic stroke, that mechanism can be disrupted in the affected hemisphere for about a week. During that period, aggressive blood-pressure lowering can reduce blood flow to vulnerable tissue and worsen outcomes.
That is why the OPTIMAL-BP trial in JAMA, which studied intensive blood-pressure lowering in the first 24 hours after endovascular thrombectomy, found harm in that setting. The two trials are not contradictory; they tested different clinical situations.
OPTIMAL-Stroke, by contrast, enrolled only patients who were clinically stable for at least 48 hours after their index event, and most were enrolled months after their stroke or TIA. By then, autoregulation has generally returned, so the acute-phase concern no longer applies.
Kidney Effects Need Monitoring
The trial did uncover a trade-off: kidney-related adverse events were more common in the intensive-treatment group. That finding is consistent with prior evidence and with kidney physiology, since blood pressure is a key driver of glomerular filtration. Lowering systolic pressure below 120 mm Hg can reduce the pressure that supports kidney function. For patients with chronic kidney disease or diabetic nephropathy, that means careful individualized assessment is important.
Serious adverse events overall were similar between the two groups, so the increase in kidney-related events did not translate into a broader rise in life-threatening harm. Still, Sampaio stressed that achieving lower blood pressure safely requires proper medical supervision and close attention to kidney function.
This should not discourage stroke survivors from pursuing intensive treatment. Instead, it underscores that the approach should be guided by a physician, with kidney function checked at baseline and followed over time.
Part of a Broader Wave of Stroke-Prevention Research
OPTIMAL-Stroke arrives amid a productive period for recurrent stroke prevention research. A separate trial, TRIDENT, published earlier in the year in the New England Journal of Medicine, found that a fixed-dose pill combining telmisartan, amlodipine, and indapamide reduced recurrent stroke by about 39% in survivors of intracerebral hemorrhage. A later meta-analysis in The Lancet Neurology also confirmed that intensive blood-pressure lowering after intracerebral hemorrhage reduced recurrent stroke by 38%, with senior author Craig Anderson, MD, PhD, noting that patients already at or below the usual 130/80 target may still benefit from further optimization.
Together, these studies suggest that the long-accepted below-140 mm Hg target — and in some cases even the below-130 mm Hg target — may leave substantial preventable risk on the table for many stroke survivors. OPTIMAL-Stroke is the first randomized trial to provide definitive Level 1 evidence for the ischemic stroke population.
Earlier stroke-specific studies had pointed in the same direction, but were too small to settle the issue. RESPECT in Japan enrolled 1,263 patients and showed a hazard ratio of 0.73 for recurrent stroke with intensive blood-pressure control, but the result did not reach statistical significance. SPS3 enrolled 3,020 patients with lacunar stroke and found a 19% nonsignificant reduction in overall stroke with a target below 130 mm Hg. Both were consistent with the new findings, but neither had enough power to prove them. A meta-analysis combining RESPECT with its extension suggested a 22% reduction in recurrent stroke, a result now confirmed and exceeded by OPTIMAL-Stroke.
What It Could Mean for the United States
The American Heart Association estimates that about 185,000 of the roughly 795,000 strokes in the United States each year are recurrent events. Its guidance also says that as many as 80% of recurrent strokes may be preventable with optimal secondary prevention.
There remains a documented gap between current care and best practice. A Duke-Yale study published in Stroke found that the one-year recurrence rate among Medicare beneficiaries hospitalized for ischemic stroke fell from 11.3% in 2001-2003 to 7.6% in 2016-2017. That was a meaningful improvement, but recurrence remained concentrated in 76 counties, mainly in the South-Central region, where populations had larger shares of Black residents, greater wealth inequality, and lower preventive-care access.
If the 27% relative reduction seen in OPTIMAL-Stroke could be applied broadly, it would suggest that roughly 50,000 recurrent strokes might be prevented each year in the United States. That is only a population-level projection, not a guarantee, and it depends on whether the treatment can be used safely at scale. Still, it shows the size of the opportunity.
Guidelines and Next Steps
The current AHA/ASA secondary stroke prevention guideline recommends a blood-pressure target below 130/80 mm Hg for most stroke survivors, based largely on meta-analyses and extrapolation rather than a dedicated randomized trial in this population. The latest ACC/AHA hypertension guidance encourages targets below 120 mm Hg when tolerated, but also notes that the evidence was drawn from SPRINT rather than stroke-specific research.
OPTIMAL-Stroke now provides that missing evidence. It does not automatically rewrite guidelines, since formal updates take time and require systematic review. But it clearly shifts the discussion: there is now Level 1 randomized evidence that a systolic target below 120 mm Hg reduces recurrent stroke by about 27% in patients who have already had an ischemic stroke or transient ischemic attack.
Whether future recommendations adopt that target broadly or limit it in patients with significant chronic kidney disease or other concerns will depend on how guideline panels weigh the kidney risk. What is no longer in doubt is the central question: intensive treatment works in stroke survivors. The remaining issues are who should receive it, how closely it should be monitored, and how quickly it should be implemented.
What Stroke Survivors Should Do
The trial should not be taken as advice to change medication on your own. Reaching a systolic pressure below 120 mm Hg usually requires several drugs, careful dose adjustments, and monitoring for side effects, especially kidney problems. Lowering pressure too quickly or without supervision can cause dizziness, falls, and other complications.
What the evidence does support is a more informed conversation with a doctor. For stroke survivors whose blood pressure is currently managed to 130 or 140 mm Hg, the new data provide a strong reason to ask whether a more intensive goal below 120 mm Hg may be appropriate, with proper monitoring.
"Achieving lower blood pressure safely requires appropriate medical supervision," Sampaio said.
Handled well, that supervision could become one of the most important steps a stroke survivor takes to protect future health.
About the Trial
Trial name: OPTIMAL-Stroke (NCT04036409)
Full title: Optimal Blood Pressure for the prevenTIon of Major vAscuLar Events in Stroke Patients
Sponsor: Hospital Israelita Albert Einstein, with collaboration from Brazil's Ministry of Health
Principal investigator: Gisele Sampaio, MD, PhD, Federal University of São Paulo
Steering committee chair: Otávio Berwanger, MD, PhD, George Institute for Global Health / Imperial College London
Enrollment: 4,368 adults; 30 centers; Brazil; 2019–2022
Follow-up: Average 3.9 years
Published: New England Journal of Medicine
Presented at: AHA Scientific Sessions 2026, Chicago, IL — AHA newsroom announcement
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