What was the goal of the SPRINT study?
High blood pressure is a major public health concern because it is a very common condition and a leading risk factor for other conditions, including heart attack, heart failure, stroke, chronic, and decline. The NIH Systolic Blood Pressure Intervention Trial (SPRINT), an NHLBI-supported study, was designed to answer three important research questions about how treating to a lower blood pressure target—less than 120 millimeters of mercury (mm Hg)—affects the cardiovascular system, kidneys, and brain.
- Cardiovascular: The main cardiovascular research question in SPRINT was to understand whether treating high blood pressure to a target systolic blood pressure goal of less than 120 mm Hg was better than treating to a goal of less than 140 mm Hg, which was the commonly recommended target at the time the SPRINT study was initiated. When SPRINT was designed, observational studies showed that participants with lower systolic blood pressure levels had fewer complications and deaths due to cardiovascular diseases. But the benefits and potential side effects of treating people who had no history of diabetes or stroke to a systolic blood pressure of less than 120 mm Hg, as compared to treating to less than 140 mm Hg, had not been tested in a long-term clinical trial.
- Kidneys: SPRINT recruited a group of participants who had chronic kidney disease to see how the lower systolic blood pressure target affected their cardiovascular and kidney function.
- Brain: SPRINT Memory and Cognition IN Decreased Hypertension (SPRINT-MIND) is examining whether treating to the lower blood pressure target reduces the risk of developing dementia, slows the decline in cognitive function, and results in less small vessel disease in the brain as shown by magnetic resonance imaging (MRI).
- SPRINT included 9,361 adults age 50 or older who had systolic pressures of 130 mm Hg or higher and at least one other cardiovascular disease risk factor.
- Approximately 28 percent of the SPRINT population was age 75 or older and 28 percent had chronic kidney disease (CKD).
- SPRINT found that the lower target (less than 120 mm Hg) reduced cardiovascular events by 25 percent and reduced the overall risk of death by 27 percent.
- SPRINT helped inform the 2017 American Heart Association (AHA) and American College of Cardiology (ACC) high blood pressure clinical guidelines.
- The lower systolic target (less than 120 mm Hg) also reduced cardiovascular events and saved lives in participants who had CKD.
- SPRINT-MIND follow-up dementia and cognitive findings are expected to be published in late 2018.
What are the key findings of the SPRINT study?
SPRINT provided a major contribution to high blood pressure research. It ended early and its findings were shared when it was clear that treating to the lower target of less than 120 mm Hg reduced cardiovascular events and saved lives in all participants, including those who had CKD. Learn more about the major findings for this study’s cardiovascular and kidney research questions.
In adults age 50 and older who had high blood pressure and at least one additional cardiovascular disease risk factor, but who had no history of diabetes or stroke, SPRINT showed that treating to a target systolic blood pressure of less than 120 mm Hg reduced rates of high blood pressure complications, such as heart attack, heart failure, and stroke, by 25 percent. Compared with the standard target systolic pressure of 140 mm Hg, treating to less than 120 mm Hg also lowered the risk of death by 27 percent. In 2015, the SPRINT Research Group published its findings in the New England Journal of Medicine.
The cardiovascular benefits of the lower systolic blood pressure target were consistent in all groups of people included in SPRINT, regardless of gender, race, age, or pre-existing CKD. To achieve the target systolic blood pressure of less than 120 mm Hg, the first treatment group received three medicines on average. The second treatment group received two medicines to treat to the target systolic blood pressure of less than 140 mm Hg. Participants had high levels of satisfaction with treatment and adherence to medicines regardless of which treatment group they were in.
In the lower blood pressure group, there were expected side effects from blood pressure medicines, such as lower blood levels of potassium and sodium. Treating to the target systolic blood pressure of less than 120 mm Hg also showed an increase in complications due to low blood pressure such as fainting; however, there was not an increased risk of falls. Overall, the benefits in reducing the risk of cardiovascular disease and death outweighed the potential side effects of treating to a lower blood pressure target.
SPRINT included a large group of adults age 75 and older, and a separate analysis confirmed that treating to a lower blood pressure target reduced complications of high blood pressure and saved lives in older adults, as with the overall study population, even for older study participants who had poorer overall health. This was an important finding because a large percentage of the U.S. population age 75 and older have high blood pressure.
About 28 percent of the SPRINT participants had CKD when they started the study. Enrolling participants who had CKD allowed SPRINT investigators to see how treating to a lower blood pressure target affected cardiovascular and kidney outcomes in these participants.
Similar to the larger group, SPRINT showed that treating to the lower target goal of less than 120 mm Hg reduced high blood pressure complications for these participants. SPRINT found no difference in the main kidney outcomes—onset of end-stage renal disease or a 50 percent decline in glomerular filtration rate (GFR)—between patients in the higher or lower blood pressure treatment groups.
Participants in the lower systolic blood pressure treatment group had more episodes of acute kidney injury than those in the higher systolic blood pressure treatment group. However, most of these cases were mild and kidney function was restored.
What was the impact of the SPRINT study?
In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new comprehensive high blood pressure guidelines. SPRINT and other clinical research findings informed these new ACC/AHA guidelines, which were published in the Journal of American College of Cardiology and Hypertension. The guidelines define high blood pressure for adults as systolic readings of 130 mm Hg or higher or readings of 80 mm Hg or higher. This a change from the old guideline definition for high blood pressure, which was systolic readings of 140 mm Hg or higher or diastolic readings of 80 mm Hg or higher. The guidelines take into account decades of research on the management of high blood pressure, and SPRINT provided important evidence about the safety and effectiveness of following a more intensive treatment target in high-risk individuals.
NHLBI-supported SPRINT data continue to be used to fuel scientific discovery. As part of an NHLBI-supported data challenge launched in 2016, nearly 150 teams submitted new scientific or clinical discoveries based on their analysis of SPRINT data. The data from the SPRINT cardiovascular results paper (SPRINT Primary Outcome Paper Data – SPRINT-POP) are available in the NHLBI data repository, Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC), for further secondary analyses by the scientific community. Also visit the SPRINT trial website for regular updates of new findings from the study data and a complete list of publications based on data from the study.
How was the SPRINT study conducted?
The study included data from 9,361 adults age 50 or older with systolic blood pressure of 130 mm Hg or higher and at least one additional cardiovascular disease risk factor. Participants included men and women, members of racial and ethnic minority groups, and older adults. About 28 percent of the study participants were age 75 or older, and another 28 percent had a history of CKD. Participants with diabetes, prior stroke, or polycystic kidney disease were excluded. Participant enrollment occurred between 2010 and 2013 at 102 sites in the United States, including Puerto Rico.
The protocol for the intensive treatment group was designed to target a systolic blood pressure of less than 120 mm Hg. On average, this group received three medicines to achieve the target. The protocol for the comparison treatment group was designed to achieve a systolic blood pressure target of less than 140 mm Hg. On average, this group received two medicines to achieve the target. Medicines from the major classes of high blood pressure medicines were provided by SPRINT at no cost to the participants. The SPRINT formulary is presented in Table 2 of the published SPRINT design paper. The treatment algorithms for both arms of the trial are also available in Figures 3 and 4 of the SPRINT design paper.
SPRINT was a government-funded trial and no private companies were involved in funding the trial or developing the protocol, which was finalized in 2010. In January 2013, NHLBI signed an agreement for medicine donations with one company, Takeda Pharmaceuticals International, Inc. Takeda contributed two study medicines, azilsartan alone and azilsartan with chlorthalidone, which were two in a formulary of many high blood pressure medicines. Azilsartan is an angiotensin II receptor antagonist. Chlorthalidone is a commonly prescribed diuretic. Less than five percent of the SPRINT participants were prescribed these donated medicines. Arbor Pharmaceuticals, LLC, subsequently assumed the licensing for the Takeda drugs and thus has participated in donating these high blood pressure medicines to SPRINT.
Various classes of standard high blood pressure medicines were included in the formulary for the SPRINT trial, including diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, calcium channel blockers, and beta blockers, among others. Many SPRINT blood pressure medicines were generic medicines.
Further follow-up of SPRINT participants involves comparing the effects of the higher and lower blood pressure targets on rates of dementia and cognitive function. Researchers have performed dementia testing for all SPRINT participants during the trial. Some participants also had additional cognitive function testing and MRI scans of the brain. Researchers continue to analyze the results of these tests and are performing final cognitive assessments on SPRINT participants.
The dementia and cognitive findings are expected to be published in late 2018.
Why was the SPRINT study stopped early?
The study was monitored by an independent Data and Safety Monitoring Board (DSMB) that performed interim analyses of study results and adverse events to look for any indication that one treatment group’s results were superior to the other group. As the study progressed, it became clear that treating systolic blood pressure to a target of less than 120 mm Hg significantly reduced rates of cardiovascular events and death.
In view of the superior benefits of the lower blood pressure treatment intervention, the DSMB recommended communicating these results to study participants, investigators, and the public. The NHLBI accepted this recommendation and ended the blood pressure intervention of the SPRINT study about a year in advance of the original trial end date. Trial investigators implemented an orderly closeout process that included one last visit for participants’ blood pressure management to be transitioned back to their primary care providers.
What’s in the future for the SPRINT study?
When the SPRINT blood pressure intervention ended early, the cardiovascular results were published first, followed by additional publications on the effects of the lower blood pressure on kidney function.
Examining the effects of the lower blood pressure on dementia and cognitive functioning is ongoing at this time.
The National Institute on Aging (NIA) has funded a follow-up study of SPRINT participants called SPRINT Alzheimer’s, Seniors, and Kidney Study (SPRINT ASK). This follow-up study will evaluate participants one year after their last visit to test whether the rate of all-cause dementia and mild cognitive impairment is lower in participants who were treated to the lower systolic target of less than 120 mm Hg compared to rates in participants treated to the standard systolic target of less than 140 mm Hg. This study will also perform one more test to measure kidney function.
The dementia and cognitive findings are expected to be published in late 2018.
NIH’s landmark trial, Systolic Blood Pressure Intervention Trial (SPRINT) informed the new blood pressure guidelines by testing the effects that a lower blood pressure target has on reducing heart disease risk.