Lower BP Targets Again Affirmed in Major Trial

Lowering systolic blood pressure targets down to the 110 to less than 130 mm Hg range substantially reduced cardiovascular adverse events in the STEP randomized trial, affirming the SPRINT findings for an older, Chinese population.

Among some 8,500 patients ages 60 to 80 in China, the intensive target trimmed 26% off the composite risk of stroke, acute myocardial infarction, hospitalization for unstable angina, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes.

The rate of these events was 3.5% over a median 3.34 years on the intervention compared with 4.6% with a usual-care target of 130 to less than 150 mm Hg (P=0.007), Jun Cai, MD, PhD, of FuWai Hospital, reported at this year’s European Society of Cardiology (ESC) virtual meeting and online in the New England Journal of Medicine.

Cai speculated that the findings from now a second major trial supporting a lower target could unite the guidelines, which even among U.S. professional societies range from thresholds of 130 to 150 mm Hg.

The findings overall showed similarity to those of the landmark SPRINT trial, which compared targets of less than 120 with less than 140 mm Hg — with the exception of which component endpoints were significantly improved.

In STEP, intensively targeting blood pressure had a particularly large impact on acute decompensated heart failure, with a hazard ratio of 0.27 (95% CI 0.08-0.98), but based on only three versus 11 cases.

The reduction was also significant for stroke (HR 0.67, 95% CI 0.47-0.97) and acute coronary syndrome (HR 0.67, 95% CI 0.47-0.94).

SPRINT found no significant impact on stroke or acute coronary syndrome and a more modest heart failure reduction but a 27% relative reduction in all-cause mortality. In STEP, death from cardiovascular causes was numerically but not significantly lower with the intensive blood pressure target (HR 0.72, 95% CI 0.39-1.32), while all-cause mortality was similar between groups (1.6% vs 1.5%, respectively).

Generalizability

The reason for the lack of impact on mortality might have been the fairly healthy population in the Chinese trial, suggested Rajiv Agarwal, MD, of Indiana University in Indianapolis, who was not involved in the study.

STEP enrolled people ages 60 to 80 with a systolic blood pressure of 140 to 190 mm Hg during three screening visits or who were on antihypertensive medication. Prior ischemic or hemorrhagic stroke precluded enrollment.

The mean age of the STEP population was 66.2 years, on par with SPRINT’s 67. However, a Framingham risk score of 15% or greater was observed at baseline in 67% of STEP but 76% of SPRINT participants. In STEP, only about 2% of participants had renal dysfunction, compared with more than one third in a typical U.S. population over age 60, he noted.

“It’s a healthier population than the one I’m used to seeing,” Agarwal said. “I don’t think these data are generalizable to the United States.”

The researchers also cited differences in trial design and eligibility criteria, blood pressure targets, the geographic location, and the almost entirely Han Chinese trial population.

“I think it’s confirmation of the SPRINT study in China rather than the STEP study confirming the SPRINT study for the United States,” Agarwal told MedPage Today. “Each individually is confirming in large swaths of human population that blood pressure lowering, even among the elderly, is associated with benefits. … They have data now for more than a billion people to get treated with these drugs.”

That’s important given the considerable burden of hypertension and stroke in China, suggested NEJM editorialist Mark Nelson, MBBS, PhD, of the University of Tasmania in Hobart, Australia.

However, he did see STEP as confirmatory for SPRINT: “Perhaps instead of waiting for more evidence, we should see this as the time to act,” he wrote.

Either way, Agarwal agreed that STEP “adds to the growing body of evidence that in elderly we shouldn’t be complacent about blood pressure.”

Many older adults in Western countries struggle to reach even 140 mm Hg, and low targets might not be so well tolerated by frail elders, cautioned ESC session study discussant Bryan Williams, MD, of University College London.

“This is most likely to be possible in those who are independent, active, and less frail, like in that study, and with few comorbidities,” he concluded. “Tolerability is important in determining persistence with therapy.”

Newer Strategies

One of the concerns about the SPRINT trial was the blood pressure measurement techniques used in the trial, with variability between sites in how the automated in-office checks were done — with or without an observer in the room.

In STEP, office measurements likewise were taken in triplicate with an Omron device after 5 minutes of seated rest, but by a nurse or physician in all cases.

Williams pointed out that the achieved systolic pressures were likely quite similar between SPRINT and STEP. He pointed to an analysis of typical in-office blood pressure measurements found in outpatient electronic health records for the SPRINT patients. In it, the intensive treatment group actually came in a little under 130 mm Hg systolic by standard measurement, compared with around 120 mm Hg by the trial’s measurement protocols.

The open-label STEP trial also provided patients a validated Omron home blood pressure monitor to be used at least weekly, with measurements uploaded via Bluetooth to a smartphone app. Physicians could receive monthly reports on that data, but algorithm-based titration of medications to the randomized treatment target was based on the office readings.

Patients were provided with antihypertensive drugs, including the angiotensin-receptor blocker olmesartan, the calcium-channel blocker amlodipine, and the diuretic hydrochlorothiazide. Follow-up visits every 3 months were planned to continue for 48 months, but the trial was stopped early for efficacy.

The average blood pressure achieved by 1 year was 127.5 mm Hg in the intensive-target group and 135.3 mm Hg in the usual-care group using a mean of 1.9 medications. “This was not a hard-to-treat population,” Agarwal noted.

Safety and renal outcomes were similar between groups, including for dizziness, syncope, and fracture, except for more hypotension with the intensive target (3.4% vs 2.6%, P=0.03).

Moving toward greater utilization of home blood pressures, which were within 3 mm Hg of the office measurements in STEP, is where the field needs to go, Agarwal argued. He pointed to the SimCard trial in rural Tibet and India in which smartphone-based decision support with home monitoring reduced blood pressure levels, and the U.K. TASMINH4 trial of self-titrated antihypertensives based on home blood pressure measurements.

“We need to move out of the doctor’s office and allow management of blood pressure outside a little bit more to have the population benefits of these therapies,” Agarwal said.

Indeed, “many patients in the pandemic have purchased home monitoring devices and are very happy to do the monitoring at home,” noted ESC press conference panelist Sarah Clarke, MD, of Royal Papworth Hospital in Cambridge, England.

Last Updated August 30, 2021