A Randomized Trial of Intensive versus Standard Blood-Pressure Control

Abstract

Background: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.

Methods: We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.

Results: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.

Conclusions: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).

Figure 1. Eligibility, Randomization, and Follow-up

Discontinued intervention refers to participants who discontinued the study treatment but did not withdraw consent or become lost to follow-up.

Figure 2. Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial

The systolic blood-pressure target in the intensive-treatment group was less than 120 mm Hg, and the target in the standard-treatment group was less than 140 mm Hg. The mean number of medications is the number of blood-pressure medications administered at the exit of each visit. I bars represent 95% confidence intervals.

Figure 3. Primary Outcome and Death from Any Cause

Shown are the cumulative hazards for the primary outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or death from cardiovascular causes) (Panel A) and for death from any cause (Panel B). The inset in each panel shows the same data on an enlarged y axis. CI denotes confidence interval.

Figure 4. Forest Plot of Primary Outcome According to Subgroups

The dashed vertical line represents the hazard ratio for the overall study population. The box sizes are proportional to the precision of the estimates (with larger boxes indicating a greater degree of precision). The subgroup of no previous chronic kidney disease (CKD) includes some participants with unknown CKD status at baseline. Black race includes Hispanic black and black as part of a multiracial identification.