American Heart Association Meeting

An intensive treatment approach to lower systolic blood pressure to a target of 120 mm Hg in patients with type 2 diabetes led to a lower risk of cardiovascular events than a standard treatment approach in the BPROAD trial.

In the new Chinese clinical trial, the relative risk of a major cardiovascular event was 21% lower with intensive treatment than with standard treatment during the 4-year follow-up period.

”These findings provide strong support for a more intensive systolic blood pressure target in people with type 2 diabetes for the prevention of major cardiovascular events,” study author Guang Ning, MD, PhD, from the Ruijin Hospital at Shanghai Jiao Tong University School of Medicine in Shanghai, China, reported here at the American Heart Association (AHA) Scientific Sessions 2024. The results were simultaneously published online in the New England Journal of Medicine.

https://www.nejm.org/doi/full/10.1056/NEJMoa2412006

 

Blood pressure targets for patients with type 2 diabetes have been unclear, the authors explain. The landmark American SPRINT trial showed that intensive treatment with a systolic target of 120 mm Hg led to a significant reduction in cardiovascular events compared with the standard target of 140 mm Hg, but that trial did not include patients with diabetes.

The older ACCORD trial failed to show a significant reduction in cardiovascular events after similar intensive blood pressure lowering in people with diabetes. However, that trial was underpowered to assess blood pressure intervention and the results may have been biased by the factorial design of the glucose intervention used in the trial, report investigators.

Consistent With SPRINT

The BPROAD trial provides ”convincing evidence of the benefits of lowering systolic blood pressure to a target of less than 120 mm Hg in patients with type 2 diabetes,” report the investigators. This result is consistent with findings from the SPRINT trial, ”which showed a significant 27% lower risk of major cardiovascular disease events among patients without diabetes who received intensive blood pressure lowering.”

In addition, the ESPRIT trial ”recently showed a 12% lower risk of major vascular events among patients with and those without diabetes” who received intensive blood pressure lowering treatment, they add.

The BPROAD trial has important implications for blood pressure management in clinical practice, they explain. Although the Eighth Joint National Committee recommend a systolic blood pressure of less than 140 mm Hg in patients with type 2 diabetes on the basis of findings from the ACCORD trial, most current guidelines recommend a systolic blood pressure of less than 130 mm Hg in patients with diabetes. However, evidence supporting this recommendation has been lacking.

These results ”provide support for more intensive systolic blood pressure control in patients with diabetes for the prevention of major cardiovascular disease events. However, with intensive blood pressure targets, patients need to be monitored for hypotension” and hyperkalemia, they add.

BPROAD Trial

In the BPROAD trial, 12,821 patients aged 50 years and older with type 2 diabetes were enrolled who had elevated systolic blood pressure and were at an increased risk for cardiovascular disease at 145 clinical sites across China.

Patients were randomized to receive intensive treatment, with a systolic blood pressure target of less than 120 mm Hg, or standard treatment, with a target of less than 140 mm Hg, for up to 5 years.

The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, and death from cardiovascular causes.

After 1 year of follow-up, mean systolic blood pressure was lower with intensive than standard treatment (121.6 vs 133.2 mm Hg).

At a median follow-up of 4.2 years, fewer patients in the intensive than standard treatment group experienced a primary outcome event (393 vs 492 patients; 1.65 vs 2.09 events per 100 person-years; hazard ratio, 0.79; 95% CI, 0.69 to 0.90; P < .001).

The incidence of serious adverse events was similar in the two treatment groups. However, symptomatic hypotension occurred more frequently in the intensive than standard treatment group (8 of 6414 patients vs 1 of 6407 patients; P = .05). In addition, high serum potassium (> 5.5 mmol/L) was more common with intensive than standard treatment (2.8% vs 2.0%; P = .003).

Among secondary outcomes, stroke occurred less frequently in the intensive than standard treatment group (1.19 vs 1.50 events per 100 person-years). ”Stroke is the most common type of cardiovascular disease among Chinese persons, and hypertension is the leading contributor to stroke and stroke-related death,” the authors report.

Filled a Knowledge Gap

”The BPROAD study has filled a key gap in our knowledge about whether the SPRINT results would also apply to patients with diabetes. The answer is definitively yes. Now we have to move toward implementing these important findings in the millions of patients worldwide with diabetes,” said Amit Khera, MD, director of preventive cardiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the AHA 2024 Council on Scientific Sessions Programming.

The study confirms that people with diabetes have the same response as those without diabetes in terms of benefit from more aggressive blood pressure lowering, added Shawna Nesbitt, MD, which had been uncertain because of the unclear results of the ACCORD trial.

”It was a bit of a misnomer to find that ACCORD was positive for nondiabetics but negative for diabetics. It goes against what one would think because the risk of cardiovascular events in diabetics is obviously much higher,” said Nesbitt, who is also from UT Southwestern Medical Center.

One of the issues with the ACCORD trial was the study design had several tiers and lower-risk patients were reserved for the blood pressure component. ”This made that part of the trial a little bit more ’murky’ to understand, and we didn’t see significance,” Nesbitt pointed out.

In clinical practice, however, ”while we are very happy to see that intensive reduction of blood pressure reduces 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.

The AHA generally advises that systolic pressure be lowered to less than 130 mm Hg and diastolic pressure be lowered to 80 mm Hg. In addition, nonpharmacologic treatment should be initially used for those with a systolic blood pressure of 130-139 mm Hg and diastolic blood pressure of 80-89 mm Hg.

”However, patient age and condition must be considered when deciding how low the blood pressure should go, as we know that in elderly people, the likelihood of having a fall or having hypotension may be slightly increased. And we must be careful to monitor electrolytes and kidney function to minimize adverse events,” Nesbitt explained.

The BPROAD trial confirms that patients with diabetes should have the same blood pressure targets as patients without diabetes, Jane Leopold, MD, director of the Women’s Interventional Cardiology Health Initiative at Brigham and Women’s Hospital in Boston, Massachusetts, and deputy editor of the New England Journal of Medicine, explained in an audio interview published on the journal website.

”If anything, it is more important to reduce blood pressure to lower levels in patients with diabetes, as they have a higher risk of cardiovascular events,” she said.

However, it is extremely difficult to get patients to these lower blood pressure targets, Leopold pointed out.

”This often requires multiple medications, which come with multiple side effects, and patients don’t like taking numerous different medications. This is something that we have to continue to work on. We need to explain the benefits of lower blood pressure to patients, but at the same time, balance that with the risks of polypharmacy,” she said.

From www.medscape.com

 

Nyhetsinfo

Abstract

Background

Effective targets for systolic blood-pressure control in patients with type 2 diabetes are unclear.

 

Methods

We enrolled patients 50 years of age or older with type 2 diabetes, elevated systolic blood pressure, and an increased risk of cardiovascular disease at 145 clinical sites across China. Patients were randomly assigned to receive intensive treatment that targeted a systolic blood pressure of less than 120 mm Hg or standard treatment that targeted a systolic blood pressure of less than 140 mm Hg for up to 5 years. The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes. Multiple imputation was used for missing outcome data, with an assumption that the data were missing at random.

 

Results

Of 12,821 patients (6414 patients in the intensive-treatment group and 6407 in the standard-treatment group) enrolled from February 2019 through December 2021, 5803 (45.3%) were women; the mean (±SD) age of the patients was 63.8±7.5 years. At 1 year of follow-up, the mean systolic blood pressure was 121.6 mm Hg (median, 118.3 mm Hg) in the intensive-treatment group and 133.2 mm Hg (median, 135.0 mm Hg) in the standard-treatment group. During a median follow-up of 4.2 years, primary-outcome events occurred in 393 patients (1.65 events per 100 person-years) in the intensive-treatment group and 492 patients (2.09 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P<0.001). The incidence of serious adverse events was similar in the treatment groups. However, symptomatic hypotension and hyperkalemia occurred more frequently in the intensive-treatment group than in the standard-treatment group.

 

Conclusions

Among patients with type 2 diabetes, the incidence of major cardiovascular events was significantly lower with intensive treatment targeting a systolic blood pressure of less than 120 mm Hg than with standard treatment targeting a systolic blood pressure of less than 140 mm Hg. (Funded by the National Key Research and Development Program of the Ministry of Science and Technology of China and others; BPROAD ClinicalTrials.gov number, NCT03808311.)

 

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