CHICAGO — Intensive antihypertensive treatment aimed at targeting systolic blood pressure (BP) below 120 mm Hg may reduce the risk of stroke, heart attack or other major cardiovascular events in people who have had a stroke, but not as much in people with diabetes, according to two clinical trials.
“We were able to achieve a sustained reduction in systolic blood pressure of 13.1 mm Hg difference at 3.9 years,” said Otavio Berwanger, MD, PhD, co-senior author of the OPTIMAL-STROKE and OPTIMAL-DIABETES trials. Both trials, presented at the American Heart Association (AHA) 2026 Scientific Sessions, randomized patients to the 120 mm Hg goal or the standard 140 mm Hg goal.
The diabetes trial found a similar effect, with the intensive therapy group having a systolic BP 13.7 mm Hg lower than the standard therapy group, said Berwanger, executive director of the George Institute for Global Health in London, England. The OPTIMAL-STROKE and OPTIMAL-DIABETES trials were published simultaneously in The New England Journal of Medicine.
In the stroke trial, the intensive treatment group had a statistically significant relative risk reduction of 21.6% for the primary outcome, which was a composite of cardiovascular death, nonfatal heart attack or stroke, or hospitalization for unstable angina or heart failure (HF), Berwanger said (relative risk (HR), 0.79; 95% CI, 0.67-0.94; P. = 0.007).
The diabetes trial, in contrast, found no statistically significant difference between the two treatment groups, Berwanger said, with 6% of patients in the intensive group and 6.7% of patients in the standard treatment meeting the primary outcome, for an HR of 0.9 (95% CI, 0.77-1.06; P. = 0.2).
The diabetes trial results, however, may merit further examination, said Shawna Nesbitt, MD, MS, medical director of Parkland Health’s hypertension clinic and professor at the University of Texas Southwestern Medical Center, both in Dallas. “Longer follow-up of this population could have shown us statistically significant differences,” she said. Nesbitt is not affiliated with the study.
Both trials randomized patients 1:1 to either intensive treatment aimed at a target systolic BP of 120 mm Hg or treatment aimed at the standard goal of 140 mm Hg. OPTIMAL-Stroke randomized 4,368 patients; OPTIMAL-Diabetes randomized 9,476 patients.
OPTIMAL RACING RESULTS
Women comprised approximately 48% of the stroke study population, and the average age of participants was 64 years. Among all, 57% of patients were white, 30% mixed race and 12% black. At enrollment, the average systolic pressure was about 146 mm Hg, about 40% had diabetes, and the median time since the cardiovascular event was 1.1 years, said co-principal investigator Gisele Sampaio Silva, MD, MPH, PhD, head of neurology clinical trials at Israelita Albert Einstein Hospital in São Paulo, Brazil.
“The correct systolic target for patients with prior stroke remains unclear,” Silva said. She noted that the SPRINT trial supported a target systolic BP of less than 120 mm Hg, but this did not include patients with a prior stroke.
“And previous secondary prevention trials were either underpowered or limited to specific stroke subtypes,” she said. “So our question was simple: In patients with a prior ischemic stroke or transient ischemic attack, does a systolic goal below 120 mm Hg reduce major cardiovascular events compared to a goal below 140?
This is the case, according to Berwanger, who presented the results. At 4 years, 10.9% of the intensive treatment group and 13.5% of the standard treatment group experienced one of the composite cardiovascular events (95% CI, 0.67-0.94; P. = 0.007), Berwanger said. Patients in the intensive therapy group took an average of three medications; in the standard treatment group, they took an average of 2.2 medications.
Hierarchical secondary analysis revealed no difference between the respective groups in cardiovascular deaths (4.6% and 4.7%; HR, 0.96; 95% CI, 0.73-1.26), but a relative risk reduction of 19% in the 3-point measure of major adverse cardiovascular events (MACE), including cardiovascular deaths and nonfatal heart attacks or strokes (9.8% vs. 11.8%; HR, 0.81; 95% CI, 0.68-0.98; P. = 0.03), and a 16% risk reduction in 5-point MACE, which also included unstable angina and HF hospitalization (17.4% vs. 20.2%; HR, 0.84; 95% CI, 0.74-0.97; P. = 0.02).
When the MACE components were broken down individually, the rates of all-cause death were similar between the two groups (11.7% and 12.4%), but the rates of stroke, ischemic stroke, HF-related hospitalizations, and unstable angina were all in favor of intensive treatment. The relative risks varied between 26% and 47%. The rate of hemorrhagic strokes was higher in the intensive therapy group – 0.2% versus 0.1% – but this affected only five and three patients, respectively.
The study sheds light on lowering blood pressure in patients, which can be “very difficult,” said Cheryl Bushnell, MD, MHS, a neurologist at Wake Forest University School of Medicine in Winston-Salem, North Carolina, who was not affiliated with the study.
“A lot of times patients come out of the hospital and have carotid stenosis, middle cerebral artery stenosis and everyone is nervous about lowering their blood pressure too much. So this takes away some of the concerns that many doctors have had about cerebral perfusion,” she said.
Current guidelines call for lowering blood pressure to less than 130/80 mm Hg, Bushnell noted. “We now have evidence that maybe we could do even better in terms of cardiovascular outcomes by pushing this a little bit more.” »
OPTIMAL-DIABETES results
The diabetes trial aimed to clarify the evidence for the effect of intensive blood pressure reduction in the disease, said Karla Santo, MD, PhD, co-principal investigator. “The optimal systolic blood pressure target in patients with type 2 diabetes is still uncertain and this comes from the inconsistent results of previous trials,” said Santo, a researcher at Israelita Albert Einstein Hospital.
Two previous trials she focused on were the 2010 ACCORD-BP trial, which found that intensive blood pressure control did not reduce the incidence of cardiovascular events, and the 2024 BPROAD trial in China, which reported an opposite result.
In OPTIMAL-DIABETES, 62% of participants were women and the average age was 65 years. In total, 42% were white, 42.5% mixed race and 14.5% black. Baseline systolic BP was 146 mm Hg. Approximately 28% of patients had clinical cardiovascular disease and 4% had subclinical disease.
Systolic BP results in OPTIMAL-DIABETES followed the stroke trial: 121.8 mm Hg for intensive treatment and 135.4 mm Hg for standard treatment; as was the variation in blood pressure between groups – 13.7 mm Hg – and the number of medications – 3.2 versus 2.3, Berwanger said.
However, the primary outcome of cardiovascular death, nonfatal MI or stroke, or hospitalization for unstable angina or heart failure did not favor either group in the diabetes trial, he noted.
Likewise, Berwanger said, individual secondary outcomes were not significantly different with a few exceptions: The intensive therapy group had a lower stroke rate, 1.1% vs. 1.5%, or a 27% lower HR (HR, 0.73; 95% CI, 0.51-1.06), but a 33% higher HF hospitalization rate (1.4% vs. 1%; HR, 1.33; 95% CI, 0.92-1.93).
“This should be interpreted as a neutral trial, but it is not the only one,” Berwanger said. When the results from OPTIMAL-DIABETES are combined with those from the BPROAD and ACCORD trials, the analysis reveals a 16% reduction in the relative risk of cardiovascular events, he added.
However, Berwanger noted that in the BPROAD population in China, most cardiovascular events were strokes, “as expected in this population.” OPTIMAL-DIABETES was more similar to ACCORD-BP, in which most fatal events were coronary events. “The Brazilian population is much more similar to the North American population than the Chinese population in terms of risk profile,” he said.
“Asymmetric” results?
OPTIMAL-DIABETES had a different population than other studies it was referenced to, Nesbitt said. BPROAD was 45% female and the average age of participants was 64 years. SPRINT had 35% women and the average age of participants was 68 years old. The BPROAD trial in China also had a different ethnic population than the SPRINT trial. The larger proportion of women may have “skewed” the OPTIMAL DIABETES results from the start, she said.
“In OPTIMAL, although there is no statistically significant difference here, we see a trend starting early and continuing as the lines separate,” she said, referring to a bar graph showing the gap between the trend of the intensive and standard therapy groups widening over time. “Longer follow-up of this population could have shown us statistically significant differences,” Nesbitt said.
Comparing this to BPROAD or SPRINT, the differences appeared early in the trials and remained consistent until the end, she said. Nesbitt also noted that the 2024 ESPRIT trial concluded that aggressive targeting of blood pressure in patients at cardiovascular risk, regardless of diabetes status or history of stroke, prevented major vascular events.
OPTIMAL-DIABETES “supports rather than refutes what we have already seen in other trials about more aggressive treatment of hypertension in diabetic patients,” Nesbitt said.
The trial may require a more nuanced approach to blood pressure management in diabetic patients, she added. “Maybe we’ve grouped patients together, which isn’t always beneficial. Perhaps thinking about them in a more discrete way is something we need to consider as we move forward.”
Renal results
In both trials, patients undergoing intensive treatment had a higher rate of kidney-related complications, Berwanger said.
In the stroke trial, 3.9% of patients on intensive treatment achieved the composite renal outcome compared to 2.2% of the standard outcome…
Gn Health
