New Blood Pressure Target For Individuals at High Risk - American College of Cardiology (2024)

Background

Cardiovascular disease (CVD), specifically ischemic heart disease, stroke, and heart failure, is the leading cause of death worldwide.¹ Elevated blood pressure (BP) is a strong risk factor for CVD.² Approximately 45% of adults in the United States have or are at increased risk of developing elevated BP.³ The standard of BP management prioritizes reducing systolic blood pressure (SBP) to <130 mm Hg.⁴ Previous studies, including the SPRINT (Systolic Blood Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and RESPECT (Recurrent Stroke Prevention Clinical Outcome) trials, have investigated optimal BP goals.

The SPRINT results demonstrated that targeting SBP to 120 mm Hg improved cardiovascular (CV) outcomes in individuals at high risk without diabetes mellitus (DM).⁵ The ACCORD trial focused on testing BP in patients with DM, whereas the RESPECT trial compared BP in patients with a stroke history.^6,7 Both the ACCORD and RESPECT trials yielded statistically nonsignificant results.^6,7 However, the effect of targeting lower BP in individuals at high risk regardless of history of DM or stroke has not been investigated in a trial of >10,000 participants.

The ESPRIT (Effects of Intensive Systolic Blood Pressure Lower Treatment in Reducing Risk of Vascular Events) trial investigated the BP management goal of <120 mm Hg in a large cohort of patients with high CV risk, of which a substantial percentage had DM or previous stroke history.⁴

Methods

The ESPRIT trial was an open-label, randomized trial with blinded outcomes involving participants from 116 hospitals and community medical centers across China.⁴ A total of 11,255 individuals ≥50 years of age with hypertension who were determined to be at high risk of CVD with at least two other major risk factors (age, DM, dyslipidemia, smoking) were randomized from September 2019 to July 2020 to either an intensive SBP treatment target (<120 mm Hg) or the standard SBP treatment target (<140 mm Hg).⁸

Individuals with secondary hypertension, 1-min standing BP <110 mm Hg, scheduled revascularization within the next 5 months, systolic dysfunction with ejection fraction <35%, and chronic kidney disease with estimated glomerular filtration rate <45 mL/min/1.73 m2 were excluded. Participants were followed at 1, 2, and 3 months following randomization and every 3 months thereafter for a median of 3.4 years. The primary outcome was major CV events, including myocardial infarction, revascularization, hospitalization for heart failure, stroke, or death from CV events (Figure 1).⁴

Figure 1: The ESPRIT Trial Results of Blood Pressure Target 120 mm Hg vs. 140 mm Hg

Main Findings

At baseline, the two cohorts shared similar demographics, including mean age 64.6 years. Across the entire group of participants, 29% had a history of coronary heart disease, 39% had DM, and 27% had experienced a stroke.⁴ The baseline SBP in both the intensive-treatment and standard-treatment groups was approximately 147 mm Hg. Over the course of the trial, the mean SBP in the intensive-treatment group decreased to 119 mm Hg, whereas the mean SBP in the standard-treatment group decreased to 135 mm Hg.⁴

Major CV events occurred in 547:5,624 participants (9.7%) in the intensive-treatment (120 mm Hg) group and in 623:5,631 participants (11.1%) in the standard-treatment (140 mm Hg) group.⁴ These findings yielded a hazard ratio (HR) of 0.88 (95% confidence interval [CI], 0.78-0.99; p = 0.028), a 12% relative risk for the standard-treatment group. There were 59 deaths from CV causes in the intensive-treatment group (1.1% of patients) and 97 in the standard-treatment group (1.7% of patients) (HR, 0.61; 95% CI, 0.44-0.84). In an exploratory analysis, the risk difference was also observed for a period after the 1-year mark and yielded a HR of 0.78 (95% CI, 0.67-0.9), a relative risk of 22% among the standard-treatment group.⁴ The only notable difference in adverse events was rare syncope, which occurred more frequently in the intensive-treatment group (24:5,624 patients [0.4%]) than in the standard-treatment group (8:5,631 patients [0.1%]).⁴ Overall, there was minimal difference in other adverse events and minor excess risk between treatment groups.

Implications

The ESPRIT trial results demonstrated that an intensive-treatment goal of BP <120 mm Hg reduced major CV events compared with the standard-treatment goal of BP <140 mm Hg.⁴ The investigators enrolled patients in both hospitals and community medical settings in China who had high BP while at an increased CV risk. This is consistent regardless of the history of DM or stroke. Unlike the SPRINT, this trial included a large number of persons with DM.

The SPRINT investigators reported a greater relative risk reduction of the primary composite outcome.⁵ However, the primary outcome of the ESPRIT trial differed from that of the SPRINT with the inclusion of coronary and noncoronary revacularizations.⁴ When revascularization was removed from the primary endpoint, the HR was 0.84, which is closer to the SPRINT results of HR 0.75.^4,5

The strengths of the ESPRIT trial were its very large sample size, high adherence to the intervention, limited number of patients lost to follow-up, and large number of clinical outcomes, all of which helped ensure the trial's validity. The limitations included the lack of ethnic diversity within the entirely Chinese study population.

In summary, prioritizing a SBP target of 120 mm Hg in individuals at high risk with or without DM improves CV outcomes with minimal adverse events. These findings offer new insight to clinical providers, raise awareness of optimal BP targets for individuals at high risk, and should encourage further improvements in BP through continued lifestyle improvement when patients' mean SBP remains >120 mm Hg.

References

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2. Magnussen C, Ojeda FM, Leong DP, et al.; Global Cardiovascular Risk Consortium. Global effect of modifiable risk factors on cardiovascular disease and mortality. N Engl J Med 2023;389:1273-85.
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4. Liu J, Li Y, Ge J, et al.; ESPRIT Collaborative Group. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial. Lancet 2024;404:245-55.
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8. Rahimi K. Mounting evidence in favour of the lower, the better blood pressure paradigm. Lancet 2024;404:216-7.