SPRINT finds lower systolic BP targets associated with better outcomes in nondiabetic adults at high CV risk

Nondiabetic adults at high risk for cardiovascular (CV) events may benefit from lower systolic blood pressure (BP) targets (<120 mm Hg vs. <140 mm Hg), according to the primary results of the Systolic Blood Pressure Intervention Trial (SPRINT).

SPRINT involved 9,361 patients enrolled between November 2010 and March 2013 whose systolic BP was 130 mm Hg or higher. None of the patients were diabetic, and all were at increased CV risk using standard risk-assessment measures. The researchers randomly assigned patients to intensive treatment, defined as a systolic BP target of less than 120 mm Hg, or standard treatment, defined as a systolic BP target of less than 140 mm Hg. The study's primary outcome was a composite of myocardial infarction, other types of acute coronary syndromes, stroke, heart failure, or death from CV causes. The trial was stopped early after 3.26 years of follow-up because of a significantly lower rate of the primary outcome in the intensive treatment group, and the results were published online by the New England Journal of Medicine on Nov. 9.

Of the 9,361 study patients, 28% were women, 57.7% were non-Hispanic white, 10.5% were Hispanic, 29.9% were non-Hispanic black, and 1.9% were another race or ethnic group. Overall, 31.5% of patients reported being of black race, including those who were Hispanic black and those who were multiracial. Data on race and ethnicity were self-reported. A total of 4,678 patients were assigned to the intensive treatment group, and 4,683 were assigned to the standard treatment group. Patients' antihypertensive regimen at baseline was adjusted accordingly after assignment to a study group, based on treatment algorithms. Some of the drugs used in the study were donated by pharmaceutical companies. Patients had monthly appointments for the first 3 months of the study and then were seen every 3 months.

At 1 year, mean systolic BP was 136.2 mm Hg in the standard treatment group versus 121.4 mm Hg in the intensive treatment group. The rate of the primary outcome at 3.26 years of follow-up was 1.65% per year in the intensive treatment group versus 2.19% per year in the standard treatment group (hazard ratio for intensive treatment, 0.75; 95% CI, 0.64 to 0.89; P<0.001), and the intensive treatment group also had significantly lower all-cause mortality (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Serious adverse events occurred in 38.3% of the intensive treatment group and 37.1% of the standard treatment group (hazard ratio with intensive treatment, 1.04; P=0.25); rates of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure were higher in the intensive treatment group, but rates of injurious falls and bradycardia were not. Serious adverse events classified as possibly or definitely related to the intervention occurred in 220 intensive treatment patients and 118 standard treatment patients (4.7% vs. 2.5%; hazard ratio, 1.88; P<0.001).

The authors noted that their study will be compared with the ACCORD trial, which used the same systolic BP targets but did not find significant cardiovascular or mortality benefits with the lower value, and pointed out several differences between the trials. ACCORD enrolled only patients with diabetes and had a smaller sample size and younger patients, while SPRINT included only nondiabetic patients as well as patients with chronic kidney disease. The 2 trials had design differences as well, the authors wrote. Regarding their own trial, the authors noted that the results may not be universally generalizable and that adults in nursing homes and assisted living facilities were not included, among other limitations. They also pointed out that it may be difficult to control BP to the level targeted by the intensive treatment group outside of a clinical trial, necessitating “increased medication costs and clinic visits.”

The authors of an accompanying editorial said that SPRINT offers strong support for basing treatment decisions on absolute risk levels and that a systolic BP goal of 120 mm Hg or less is appropriate for patients at high CV risk. Getting to that goal, the editorialists said, will require “substantial effort and resources,” including incentives on the population level, new therapies, and multipronged interventions. “SPRINT redefines blood-pressure target goals and challenges us to improve blood-pressure management,” the editorialists wrote. “Success will require a marathon effort.”

A systematic review and meta-analysis published last week by the Lancet looked at the effect of intensive BP lowering on cardiovascular and renal outcomes by examining trials published between Jan. 1, 1950, and Nov. 3, 2015. In 19 trials of 44,989 participants, involving 2,496 major cardiovascular outcomes over a mean of 3.8 years of follow-up, the authors found reductions in relative risk for major cardiovascular events, myocardial infarction, stroke, albuminuria, and retinopathy progression with intensive therapy but no definite effect on heart failure, cardiovascular death, total mortality, or end-stage kidney disease. Despite the study's limitations, including its lack of individual-patient data, the authors concluded that evidence clearly supports lower systolic BP targets, including in high-risk patients.

The author of an accompanying comment said that the study provides strong evidence supporting lower BP targets and noted that its results would probably be further supported by SPRINT. The comment author did point out that lower BP targets may not make sense in all patient populations. “In particular, it is not yet obvious that patients with diabetes mellitus, or very elderly patients, will benefit from lower treatment targets than the recommended goal of lower than 140/90 mm Hg,” he wrote. “Thus, the definition of new blood pressure treatment targets will not be an easy task, in terms of comorbidity and a specific mm Hg target.”