Systolic Blood Pressure Intervention Trial (SPRINT) Study

In adults aged 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 lowering blood pressure 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.

SPRINT is the first clinical trial to demonstrate that something can be done to prevent mild cognitive impairment (MCI) which is often a precursor of dementia. Participants who were treated to reduce systolic blood pressure to 120 mm Hg had about a 20% reduction in mild cognitive impairment compared to participants who were treated to 140 mm Hg.

While the more intensive blood pressure treatments to 120 mmHg or less led to a lower chance of developing MCI, it did not have the same effect on dementia. In SPRINT, treating patients to a systolic blood pressure goal of 120 mm Hg or less compared with a goal of 140 mm Hg did not significantly reduce the risk of developing dementia. Because dementia takes longer to develop, SPRINT is following up with the study participants to see whether intensive blood pressure treatments lower the risk of developing dementia in the long term. In 2019, the SPRINT Research Group published its findings in the Journal of the American Medical Association.

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.