STEP Trial Findings Build on SPRINT Results, With a Twist

STEP findings build on those from the SPRINT trial, seemingly confirming that intensive treatment for hypertension can reduce the risk of serious adverse cardiovascular (CV) outcomes. However, there was no significant benefit toward risk for all-cause and CV-related mortality.

Results presented August 30, during ESC Congress 2021, show that intensive treatment for blood pressure (BP) control can both reduce the risk of adverse cardiovascular (CV) outcomes, including heart failure, and mean systolic blood pressure (SBP).

These findings from the STEP (STrategy of blood pressure intervention in the Elderly hypertensive Population) trial seemingly confirm 2015 results from the SPRINT (Systolic Blood PRessure INTervention) trial,1 with both trials being stopped early—SPRINT at a median 3.26 years and STEP at 3.34 vs original plans of 5 and 4 years, respectively1,2—due to clear CV benefit from intensive BP control.

However, the new results do deviate from SPRINT in that there was no perceived risk reduction for all-cause and CV-related mortality, with just a 28% drop (HR, 0.72; 95% CI, 0.39-1.32) seen for CV-related death but an 11% increase (HR, 1.11; 95% CI, 0.78-1.56) seen for all-cause death.2 SPRINT, meanwhile, had 42% (HR, 0.58; 95% CI, 0.39-0.84) and 25% (HR, 0.75; 95% CI, 0.61-0.92) drops, respectively.

Results for STEP, published simultaneously in New England Journal of Medicine, show there was an overall 26% risk reduction for the primary outcome (HR, 0.74; 95% CI, 0.60-0.92; P = .007) in the intensive-treatment vs standard-treatment group.2

The primary composite outcome for STEP, a multicenter randomized clinical trial, was incidence of ischemic/hemorrhagic stroke, acute coronary syndrome (ACS; acute myocardial infarction or unstable angina hospitalization), acute decompensated heart failure, coronary revascularization, atrial fibrillation, and death from CV causes.

In-office BP measurements were taken via validated Omron electronic sphygmomanometer and home-based measures were self-collected through a smartphone app with Bluetooth connection to an Omron BP monitor. Patients, all with hypertension, aged 60 to 80 years (recruited from January 10 through December 31, 2017, at 42 clinical centers throughout China), were assigned 1:1 to 2 cohorts, each with a different SBP target2:

  • Intensive-treatment participants (n = 4243) had an SBP target range of 110 to <130 mm Hg
  • Standard-treatment participants (n = 4268) had an SBP target range of 130 to <150 mm Hg

“Hypertension is a common risk factor for death from cardiovascular causes worldwide and in China,” the authors wrote. “Yet, current guideline-based recommendations for the systolic blood-pressure target in older patients remain inconsistent.”

Individually for each of the primary outcome’s components, heart failure came out on top with an outstanding 73% reduced risk. This was followed by stroke and ACS, both which saw a 33% risk reduction (stroke: 95% CI, 0.47-0.97; ACS: 95% CI, 0.47-0.94), and major adverse cardiac events (MACE) and CV-related mortality, which each had a 28% risk reduction (MACE: 95% CI, 0.56-0.93; CV-related mortality: 95% CI, 0.39-1.32).2

Meanwhile, at the 1-year mark, the mean SBP for the intensive-treatment group was 127.5 vs 135.3 mm Hg for the standard-treatment group. These did not vary far from the means seen over the entire 3.34-year follow-up, which were 126.7 and 135.9 mm Hg, respectively. However, the overall decrease from baseline was almost twice as great for the intensive-treatment vs the standard-treatment group: 19.4 vs 10.1 mm Hg. Close to 78% of the intensive-treatment group had reached the goal range at 3 years of follow-up, and 3.5% vs 4.6% of the standard-treatment group had any of the primary-outcome events during the 3.34-year follow-up.2

There was no difference in risk reduction for coronary revascularization and atrial fibrillation, incidence of hypotension was higher in the intensive-treatment group, and renal and safety outcomes did not significantly differ.2

In the press conference announcing the findings, senior author Jun Cai, MD, PhD, director of the Hypertension Center at FuWai Hospital in Beijing, stated, “These data underscore the importance of a lower SBP target in older patients with hypertension. We recommend that in older patients treated for hypertension, systolic blood pressure should be lowered to < 130 mm Hg.”3

Yet, an accompany editorial raised some questions. For example, why were patients with a history of stroke excluded from analysis and why was quality of life not evaluated?4

Noting that not only were both trials about BP control for persons with hypertension, but that they also focused on treating elevated BP in the context of CV risk, author Mark R. Nelson, MB, BS, MFM, PhD, from Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia, wrote, “We continue to manage blood pressure as an isolated risk factor rather than as an integrated part of a patient’s risk profile because we adhere to the rusted-on clinical concept of hypertension. The approach of focusing on the absolute risk of adverse cardiovascular events has been promoted for decades from the Antipodes. Perhaps the STEP trial is another impetus for broader adoption of this approach.”4

The STEP authors appear to agree with that approach, noting a principal limitation on their findings was not including patients with a stroke history and cautioning against generalizability of their findings because of that.2

References

1. The Sprint Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116.doi:10.1056/NEJMoa1511939

2. Zhang W, Zhang S, Deng Y, et al. Trial of intensive blood-pressure control

in older patients with hypertension. N Engl J Med. Published online August 30, 2021. doi:10.1056/NEJMoa2111437

3. Cai J. STEP study: intensive vs standard blood pressure control among older hypertensive patients. Presented at: ESC Congress 2021; August 27-30, 2021. Accessed September 2, 2021. https://escardio.app.box.com/s/umpd65eagtipci89j1yuy7lqwt5w9il9/file/852949292511

4. Nelson MR. Moving the Goalposts for Blood Pressure — Time to Act. N Engl J Med. Published online August 30, 2021. doi:10.1056/NEJMe2112992