The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract

Background High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. Purpose To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. Methods SPRINT is a multi-center, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. SPRINT recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first occurrence of a myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease, incident dementia, decline in cognitive function, and small-vessel cerebral ischemic disease. Results Between November 11, 2010 and March 15, 2013 SPRINT recruited and randomized 9361 people at 102 clinics, including 3333 women, 2648 with chronic kidney disease, 1877 with a history of cardiovascular disease, 3962 minorities, and 2636 ≥75 years of age. Limitations Although the overall recruitment target was met, the numbers recruited in the high-risk subgroups were lower than planned. Conclusions SPRINT will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants, including those with prior cardiovascular disease, chronic kidney disease, and those aged ≥75 years.

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

“…However, the BP range may be arbitrary and, thus, will need to be confirmed in randomized controlled trials. This will be clarified by the ongoing SPRINT‐MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension Study),41 which is testing the effects of lowering SBP to a target goal of <120 mm Hg, compared with <140 mm Hg, on incident dementia and cognitive decline in middle‐aged and older adults with increased cardiovascular risk.…”

Effects of Intensive Systolic Blood Pressure Lowering on Cardiovascular Events and Mortality in Patients With Type 2 Diabetes Mellitus on Standard Glycemic Control and in Those Without Diabetes Mellitus: Reconciling Results From ACCORD BP and SPRINT

“…A major exclusion criterion was presence of diabetes mellitus. Further details of SPRINT inclusion and exclusion criteria were published elsewhere and are provided in the supplement 10, 11…”

“…Additional monthly visits could be scheduled for drug titration to meet the assigned SBP goal. Blood pressure measurement and SBP goals were similar to those used in the ACCORD BP trial 10, 11. A decision to stop the SPRINT intervention was made August 20, 2015, because of beneficial effects of the intensive SBP reduction 11.…”

“…In SPRINT (Systolic Blood Pressure Intervention Trial), which tested the same SBP targets in patients without diabetes mellitus,10, 11 the BP intervention was stopped early because intensive SBP lowering resulted in a substantial reduction in both the primary composite CVD end point and all‐cause mortality.…”

Systolic Blood Pressure Response in SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes): A Possible Explanation for Discordant Trial Results

“…The SPRINT and ACCORD trials have been described previously 2, 3, 9, 10. Briefly, SPRINT was a randomized multicenter trial to determine whether an intensive control strategy (SBP <120 mm Hg) was superior to a standard strategy (SBP <140 mm Hg) among 9361 nondiabetic participants aged ≥50 years at increased cardiovascular risk.…”