CHICAGO, IL—Aggressive blood-pressure control to a target of less than 120 mmHg in hypertensive patients with a prior ischemic stroke or transient ischemic attack (TIA) significantly cuts the risk of major adverse cardiovascular events compared with a target of less than 140 mmHg, results of the OPTIMAL-STROKE study show.
Reducing systolic BP to the aggressive target reduced the relative risk of the study’s primary outcome—a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina or heart failure—by 21% compared with a treatment goal of less than 140 mmHg, researchers reported recently at the American Heart Association (AHA) Scientific Sessions.
“We had one price to pay that offset the benefit, [which] was a potential increase in the composite renal endpoint,” said senior investigator Otavio Berwanger, MD, PhD (George Institute for Global Health UK/Imperial College London, England), during an AHA press conference. “But, that [renal endpoint] was primarily driven by a sustained drop in renal function, potentially a hemodynamic effect.”
There was no increased risk of end-stage renal disease, dialysis, or renal mortality, which are far more serious outcomes than reductions in kidney function, said Berwanger.
The US guidelines currently recommend that clinicians treat to a target of less than 130/80 mmHg in patients with prior ischemic stroke or TIA. In Europe, the hypertension guidelines recommend a systolic target of 120 to 129 mmHg, if tolerated.
Cheryl Bushnell, MD (Wake Forest University School of Medicine, Winston-Salem, NC), called OPTIMAL-STROKE a landmark trial, one with large implications for public health. Based on data from the Blood Pressure Lowering Treatment Trialists’ Collaboration, a 5-mmHg reduction in systolic BP leads to a 13% reduction in stroke.
We had one price to pay that offset the benefit, [which] was a potential increase in the composite renal endpoint.
Otavio Berwanger, MD, PhD
In 2015, the SPRINT investigators showed that lowering systolic BP to a target of less than 120 mmHg versus 140 mmHg reduced the risks of fatal and nonfatal major cardiovascular events, as well as all-cause mortality, in hypertensive patients with increased cardiovascular risk but without type 2 diabetes. The trial, however, excluded patients with a prior ischemic stroke or TIA.
“There are a lot of times when patients are discharged from the hospital, and they might have a carotid stenosis, a middle cerebral artery stenosis, and everybody is nervous about lowering their blood pressure too much,” said Bushnell. “[OPTIMAL-STROKE] kind of abolishes some of the concerns that a lot of neurologists and primary-care physicians have had on cerebral perfusion.”
In the sister OPTIMAL-DIABETES trial, which also randomized patients to intensive and standard targets (less than 120 and 140 mmHg, respectively), investigators found that treating to the intensive target did not reduce the risk of major cardiovascular events compared with the less stringent goal.
“This should be interpreted as a neutral trial but it’s not the only trial,” said Berwanger, referring to BPROAD and ACCORD-BP, which were similar studies. “Potentially, there is a reduction in cardiovascular events in this [diabetic] population, but the events are attenuated, the events are of lower magnitude.”
Both OPTIMAL-STROKE, led by Gisele Sampaio Silva, MD, PhD (Hospital Israelita Albert Einstein, São Paulo, Brazil), and OPTIMAL-DIABETES, led by Karla Santo, MD, PhD (Hospital Israelita Albert Einstein), were published simultaneously in the New England Journal of Medicine.
OPTIMAL-STROKE Details
OPTIMAL-STROKE included 4,368 adults (mean age 63.9 years; 47.9% women) with elevated BP and a previous ischemic stroke or TIA and randomized them to intensive or standard treatment. In the intensive arm, the BP target was less than 120 mmHg versus less than 140 mmHg in the standard arm. Nearly 92% of patients qualified for the trial with a prior ischemic stroke.
Excluding the first 3 months, the mean systolic BP at 48 months was 122.0 mmHg and 135.2 mmHg in the intensive and standard arms, respectively. This translated into a between-group mean difference of 13.1 mmHg. The percentage of patients who achieved the target of less than 120 mmHg increased from 55.0% at 12 months to 68.9% at 36 months. The intensive-therapy participants were prescribed more antihypertensive medications (mean 3.0 versus 2.2 with standard therapy).
After a median follow-up of 3.9 years, the primary outcome occurred in 10.9% of those randomized to intensive therapy versus 13.5% in the standard-therapy group (HR 0.79; 95% CI 0.67-0.94). The 3-point MACE endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke occurred in9.8% and 11.8% of the intensive- and standard-therapy arms (HR 0.81; 95% CI 0.68-0.98). A composite endpoint that included all-cause mortality, nonfatal MI/stroke, or hospitalization for unstable angina or heart failure was also significantly reduced (HR 0.84; 95% CI 0.74-0.97).
All secondary endpoints were tested according to a prespecified hierarchical sequence, and with no difference in the risk of cardiovascular mortality between treatment arms, formal testing was stopped. Stroke, ischemic stroke, MI, and hospitalizations trended in favor of the intensive treatment, however. Hemorrhagic stroke went in the other direction, but numbers were small (5 versus 3 events with intensive and standard treatment, respectively).
The composite renal outcome, which included a sustained reduction of 50% or more in the estimated glomerular filtration rate (eGFR), eGFR less than 15/ml/min/1.73 m2, long-term dialysis, or kidney transplantation, occurred in 3.9% and 2.2% of patients in the intensive and standard BP-lowering groups (HR 1.76; 95% CI 1.24-2.50). As noted, the increase was driven by more patients in the intensive-therapy group experiencing the sustained reductions in eGFR.
Clinical Implications
Daichi Shimbo, MD (Columbia University Irving Medical Center, New York, NY), the discussant following the presentation, said these results build on those from ESPRIT, a large trial of more than 11,000 patients in China. There, treating BP to less than 120 mmHg reduced the risk of MACE compared with a target of less than 140 mmHg. Roughly 25% of the study group had a history of stroke.
With OPTIMAL-STROKE, Shimbo pointed out that the number needed to treat to prevent one primary-outcome event is 38, while the number needed to harm, if the composite renal event is considered an adverse event, is 59.
“What this means is that if you treat 1,000 patients for a median of almost 4 years, 26 will benefit but 17 will be harmed,” said Shimbo. “The question I have is whether clinicians will feel comfortable with this risk-benefit ratio. Of course, the benefit is a MACE reduction, and the risk is just a creatinine bump, but I do wonder how clinicians will feel about this trial.”
The question I have is whether clinicians will feel comfortable with this risk-benefit ratio.
Daichi Shimbo
To Cardiology Now News, Bushnell said she has no concerns about lowering BP to less than 120 mmHg in patients with a prior stroke. Before OPTIMAL-STROKE, she’d aimed for less than 130 mmHg, and now won’t have many qualms getting most of these patients down below 120 mmHg. “Patients sometimes get nervous, thinking 120 [mmHg] is too low, but it’s just an adjustment.”
Jordana Cohen, MD (University of Pennsylvania Perelman School of Medicine, Philadelphia), a nephrologist, pointed out that the SPRINT researchers also looked at biomarkers of kidney injury with intensive blood-pressure lowering. Hemodynamic changes were evident, but there was no significant injury to the kidneys with the intensive approach, said Cohen.
Berwanger acknowledged that it is challenging to treat patients to less than 120 mmHg. “It takes a while for patients to get to target,” he said. Pragmatic BP-lowering strategies and single-pill combinations, as well as research into how best to implement clinical trial findings into the real world, will be important for applying their results in practice.
OPTIMAL-DIABETES
In the OPTIMAL-DIABETES trial, which included 9,476 patients (mean age 64.7 years, 62.0% women), patients were also assigned to a target of less than 120 mmHg or standard care with a goal less than 140 mmHg.
Excluding the first 3 months, the mean between-group difference in BP at 48 months was 13.7 mmHg, with the standard-therapy group achieving a mean BP of 135.4 mmHg and the intensive BP group getting down to a mean of 121.8 mmHg. On average, patients in the intensive arm were taking 3.2 antihypertensive medications compared with 2.3 in the standard-therapy group.
The primary composite outcome, the same as in OPTIMAL-STROKE, occurred in 6.0% and 6.7% of patients in the intensive- and standard-treatment arms, respectively (HR 0.90; 95% CI 0.77-1.06). Formal testing was stopped after the nonsignificant primary outcome.
During the late-breaking trial session, Berwanger presented data that combined BPROAD, ACCORD-BP, and OPTIMAL-DIABETES. Of the 3 studies, all of which tested whether there was any benefit to lowering BP to less than 120 mmHg in patients with diabetes, only BPROAD showed the intensive-treatment strategy reduced MACE although the other two trended favorably. In the meta-analysis, there was a significant reduction in the risk of MACE (HR 0.84; 95% CI 0.77 to 0.93).
“Obviously, [OPTIMAL-DIABETES] needs to be interpreted as a neutral trial, but maybe the totality of the evidence warrants a more nuanced interpretation,” said Berwanger.
Shawna Nesbitt, MD (UT Southwestern Medical Center, Dallas, TX), who spoke with the media, noted that the event curves in OPTIMAL-DIABETES separated at roughly 1 year, and “the question is whether longer follow-up may have shown us statistical significance.” Like Berwanger, Nesbitt said that OPTIMAL-DIABETES, when viewed alongside BPROAD and ACCORD-BP, “supports, rather than refutes, what we have already seen in other trials, [and] treating hypertensive patients with diabetes more aggressively.”
Source:
Sampaio Silva G, Machline-Carrion MJ, Santo K, et al. Intensive blood-pressure control in patients with previous ischemic stroke. N Engl J Med. Published online November 7, 2026.
Santo K, Martins E, Silva GS, et al. Intensive blood-pressure lowering in patients with type 2 diabetes. N Engl J Med. Published online November 7, 2026.
Disclosures:
Berwanger reports research funding from Bayer and S.Assis.
Bushnell reports consulting for Bayer.
Sampaio Silva reports serving as an advisor to Bayer and Boehringer Ingelheim. She reports research funding from the Brazilian Ministry of Health.
Santo reports research funding from Elfie and conference support from Servier.
Nesbitt and Cohen report no conflicts of interest.