CHICAGO, IL -- Intensively treating systolic blood pressure below 120 mm Hg reduces the risk of major cardiovascular events over 4 years in patients with type 2 diabetes and hypertension compared with the standard protocol of less than 140 mm Hg, according to the BPROAD trial.

The results are in line with those of the 2015 SPRINT trial, which did not include diabetic patients and led to the 2017 US hypertension guidelines lowering the treatment goal below 130/80 mm Hg. The latest European guidelines, published in September, also shifted systolic BP treatment targets below 130 mm Hg.

"We recommend patients with diabetes be intensively treated with blood pressure less than 120," said Guang Ning, MD, PhD (Shanghai Jiaotong University School of Medicine, China), who presented the results today in a late breaking trials session at the American Heart Association (AHA) 2024 Scientific Sessions.

The study was simultaneously published in the New England Journal of Medicine.

Notably, the findings contrast with the 2010 ACCORD trial, which enrolled diabetic patients but differed in that it looked at both lipid control and blood pressure lowering, failing to find a difference in cardiovascular events based on the latter.

"That made the blood pressure component of the study a little more murky to try and understand," Shawna Nesbitt, MD (UT Southwestern Medical Center, Dallas, TX), told TCTMD in a media briefing. "This trial now confirms that diabetics actually have the same response as nondiabetics in terms of blood pressure treatments."

Speaking with TCTMD, John McEvoy, MBBCh (University of Galway, Ireland), who served as the co-chair of the ESC hypertension guidelines, said he was "pleasantly surprised" by the BPROAD findings. "The ESC guideline that came out in August recommended that diabetics be treated to the same targets as others with high cardiovascular disease risk. And so, from that point of view, it was pleasing to see the results of BPROAD."

Intensive Lowering Wins

Ning and colleagues, including first author Yufang Bi, MD, PhD (Shanghai Jiao Tong University School of Medicine), enrolled 12,821 Chinese patients (mean age 63.8 years; 45.3% women) with type 2 diabetes and either a systolic BP of ≥ 140 without medication or ≥ 130 with one or more medications between February 2019 and December 2021. Patients also were considered to be at elevated risk for CVD, defined as having had a clinical CVD event within the prior 3 months or subclinical CVD event within the prior 3 years, having at least two risk factors, or having chronic kidney disease with an eGFR 30-59 ml/min/1.73 m of body surface area.

In total, 6,414 patients were randomized to an intensive systolic BP lowering strategy (< 120 mm Hg) and 6,407 were assigned to a standard protocol (< 140 mm Hg); clinicians could choose whichever antihypertensive medication and dose they thought best. Mean baseline systolic BP in both groups was about 140 mm Hg, dropping to 133.2 and 121.6 mm Hg, respectively, in the standard and intensive cohorts by 1 year. Approximately 60% of patients in the intensive-treatment group met the systolic BP target by 1 year.

Now we have to work towards implementing these important findings into millions of individuals worldwide with diabetes. Amit Khera

Over a median follow-up period of 4.2 years, the rate of the composite primary endpoint -- nonfatal stroke, nonfatal MI, treated or hospitalized heart failure, or cardiovascular death -- was lower in those treated according to the intensive versus the standard strategy (1.65 vs 2.09 events per 100 person-years; HR 0.79; 95% CI 0.69-0.90). The findings were driven by a reduction in fatal or nonfatal stroke in the intensive-treatment group (1.19 vs 1.50 events per 100 person-years; HR 0.79; 95% CI 0.67-0.92). The results were consistent across subgroup analyses.

While rates of serious adverse events were similar between the cohorts at about 36%, the researchers did note a greater incidence of both symptomatic hypotension (0.1% vs <0.1%; P = 0.05) and hyperkalemia (serum potassium > 5.5 mmol/L in 2.8% vs 2.0%; P = 0.003) among patients randomized to intensive treatment.

Notably, incident albuminuria occurred in less frequently in patients randomized to intensive compared with standard treatment (11.29 vs 13.84 events per 100 person-years; HR 0.87; 95% CI 0.77-0.97).

"Our results with respect to the primary outcome provide support for more-intensive systolic blood-pressure control in patients with diabetes for the prevention of major cardiovascular disease events," Bi and colleagues write. "However, with intensive blood-pressure targets, patients need to be monitored for hypotension, especially during the start of intensive blood-pressure reduction. Furthermore, hyperkalemia after the use of multiple antihypertensive drugs must be monitored during treatment."

Filling 'a Key Gap'

BPROAD, said Nesbitt, reaffirms what is already more broadly recommended by guidelines.

"While we are very happy to see that the results of reducing blood pressure does reduce events, we do have to be concerned about the serious adverse events that these changes in blood pressure may cause, particularly in elderly people," she said.

Notably, she pointed out that while the effects of intensive BP lowering in both SPRINT and BPROAD are "almost identical," SPRINT enrolled patients from the United States, "where there's additional diversity of population, and so that trial has a broader group than that represented from the Chinese population of BPROAD." Also, Nesbitt highlighted, the SPRINT trial showed lower potassium levels in the intensive-treatment group compared with the higher levels in the current trial.

Ultimately, "what we find here is that we have consistent evidence that lowering blood pressure to less than 120 reduces outcomes," she concluded.

There's no biological plausibility as to why diabetics would differ to others who have cardiovascular disease risk factors with respect to blood pressure treatment. John McEvoy

"There's no biological plausibility as to why diabetics would differ to others who have cardiovascular disease risk factors with respect to blood pressure treatment," McEvoy said. "So ACCORD was always an outlier and something that was inconsistent with the rest of the data from my point of view."

Notably, he pointed out that BPROAD had some advantages over ACCORD in that it was almost three times larger and also included heart failure outcomes in its primary endpoint. "So for both those reasons, it was probably more likely to show a benefit than ACCCORD was," McEvoy said. But the results shown in both BPROAD and ACCORD were driven by reductions in stroke, which "at least gave you some sense that there was consistency across the trials."

The increase in hypotension and hyperkalemia with the more intensive strategy are worth monitoring for but don't outweigh the potential CV benefits, he argued. "Most patients, if they have to choose between stroke or surviving versus a risk of hypotension and hyperkalemia, which can all be managed, would probably choose to avoid the risk of the stroke and death."

Amit Khera, MD (UT Southwestern Medical Center), who moderated the press conference, agreed. "The BPROAD study just filled a key gap in our knowledge about lower blood pressure, particularly if this concept applies to patients with diabetes," he said. "The answer is definitively yes. Now we have to work towards implementing these important findings into millions of individuals worldwide with diabetes."