BP target in diabetics: How low should we go?

Intensive blood-pressure (BP) lowering treatment targeted at a tighter systolic BP (SBP) yields cardiovascular benefits in Chinese patients with type 2 diabetes (T2D) and elevated BP in the randomized BPROAD* trial.

An SBP target of under 120 mm Hg reduced a composite of stroke, myocardial infarction, heart failure treatment or hospitalization, and cardiovascular death by a relative 21 percent than standard treatment targeting under 140 mm Hg during a median follow-up of 4.2 years, reported study author Dr Guang Ning of Shanghai Jiao Tong University School of Medicine at Shanghai, China, during a late-breaking science session at AHA 2024.

The primary-outcome events occurred less frequently in 393 patients (1.65 events per 100 person-years) in the intensive-treatment group than in 492 patients (2.09 events per 100 person-years) in the standard-treatment group (hazard ratio [HR], 0.79, 95 per cent confidence interval [CI], 0.69–0.90; p<0.001). [N Engl J Med 2024;doi:10.1056/NEJMoa2412006]

The observed difference was primarily driven by the 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 percent CI, 0.67–0.92), said Ning.  

“The benefits of intensive treatment were consistent across all prespecified subgroups,” he added.

In terms of safety, the percentage of patients who had experienced serious adverse events was similar in both groups (about 36 percent; HR, 1.00, 95 percent CI, 0.94–1.06; p=0.96). However, intensive treatment was associated with a higher incidence of symptomatic hypotension (0.1 percent vs <0.1 percent; p=0.05) and hyperkalaemia (serum potassium >5.5 mmol/L in 2.8 percent vs 2.0 percent p=0.003) compared with standard treatment.

“These are worth monitoring for but do not outweigh the potential CV benefits we observed,” said Ning.  

Notably, incident albuminuria occurred less frequently with intensive treatment (11.29 vs 13.84 events per 100 person-years; HR 0.87; 95 percent CI, 0.77–0.97).

A closer look at the BPROAD population

Effective targets for SBP control in T2D remain unclear. BPROAD enrolled 12,821 Chinese patients ≥50 years of age (mean 63.8 years, 45.3 percent female) with T2D who had elevated SBP levels (≥140 mm Hg without medication or ≥130 mm Hg with ≥1 medication) between February 2019 and December 2021.

Additionally, they were at increased risk of cardiovascular disease (CVD), defined as having had a clinical CVD event in the past 3 months or subclinical CVD event in the past 3 years, having at least two risk factors, or having chronic kidney disease with an eGFR 30–59 mL/min/1.73 m² of body surface area. Patients were randomly assigned to receive intensive treatment targeted at an SBP of <120 mm Hg (n=6,414) or standard treatment targeted at <140 mm Hg (n=6,407) for up to 5 years.

Clinicians could choose whichever antihypertensive medication and dose they thought as 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 treatment cohorts by 1 year. Approximately 60 percent of patients in the intensive-treatment group met the systolic BP target at 1 year.

Consistent with SPRINT, ESPRIT

According to Ning, the findings are consistent with those of two other trials showing benefits for lowering the SBP target to <120 mm Hg instead of a target of <140 mm Hg. Specifically, when compared with standard treatment, intensive treatment reduced the risk of major CVD events by 27 percent in high-risk patients without diabetes in SPRINT, as well as the risk of major vascular events by 12 percent in high-risk patients with hypertension, regardless of the status of diabetes or history of stroke, in ESPRIT. [N Engl J Med 2021;384:1921-1930; Lancet 2024;404:245-255]

This prompted the US and European hypertension guidelines to shift the BP treatment target to <130/80 mm Hg. [Eur Heart J 2024; 45:3912–4018] 

Contradictory with ACCORD

Interestingly, the findings from BPROAD differed from those of the 2010 ACCORD trial in diabetic patients, showing that targeting an SBP <120 mm Hg vs <140 mm Hg did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. However, according to the investigators, the trial was underpowered to assess BP intervention, and the results may have been biased by the factorial design of the glucose intervention used in the trial. [N Engl J Med 2010;362:1575-1585]

“That made the BP component of the study a little murky to try and understand,” commented Dr Shawna Nesbitt from UT Southwestern Medical Center in Dallas, Texas, US. “The current study now confirms that diabetics have the same response as nondiabetics in terms of BP treatments.”

Dr John McEvoy, Consultant Cardiologist at University College Hospital Galway, Ireland, said ACCORD was “an outlier” and that BPROAD had advantages as the population was almost three times larger and included heart failure outcomes as a primary endpoint.

“Still, 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,” he pointed out.

Implications to practice

“Our trial has important implications for BP management in clinical practice,” given that evidence supporting the recommendation of most guidelines to lower systolic BP to <130 mm Hg in patients with diabetes is lacking, said Ning. [J Am Coll Cardiol 2018;71:e127-e248; Diabetes Care 2024;47:S179-S218; J Hypertens 2023;41:1874-2071; Eur Heart J 2024;45:3912-4018]

“Our results concerning the primary outcome support more intensive SBP control in patients with diabetes to prevent major CVD events,” he added. “We recommend they be intensively treated to achieve an SBP of <120 mm Hg.”

Nesbitt, for her part, said patient age and condition must be considered when deciding how low the BP target should go. “We know that in the elderly, the likelihood of having a fall or having hypotension may be slightly increased. Additionally, we must carefully monitor electrolytes and kidney function to minimize adverse events.”

Ning agreed, adding that patients undergoing intensive BP targets must be monitored for hypotension, especially during the initiation of treatment, and for hyperkalaemia.

Dr Amit Khera, also from the UT Southwestern Medical Center, who moderated the press conference, said the BPROAD study filled a gap in clinicians’ knowledge about tighter BP targets in diabetes. “Now, we have to work towards implementing these important findings into millions of individuals worldwide with diabetes.” With reports from JAIRIA DELA CRUZ