The National Institutes of Health is launching a large multicenter randomized clinical trial to determine whether maintaining blood pressure levels lower than current recommendations further reduces the risk of cardiovascular and kidney diseases, or age-related cognitive decline.
Called the Systolic Blood Pressure Intervention Trial (SPRINT), the nine-year, $114 million study will be conducted in more than 80 clinical sites across the United States.
Current clinical guidelines recommend systolic pressure (the top number in a blood pressure reading) of less than 140 millimeters of mercury (mm Hg) for healthy adults, and 130 mm Hg for adults with kidney disease or diabetes. SPRINT will evaluate the potential benefits of maintaining systolic blood pressure at less than 120 mm Hg for adults who are at risk for heart disease or kidney disease. The study will also assess possible risks of this therapeutic strategy.
Study participants will be treated with commonly available blood pressure medications to achieve one of two different levels of blood pressure control - either less than 140 mm Hg (standard group) or less than 120 mm Hg (treatment group). Those in the treatment group will take an average of three to four medications; those in the standard group will take about two medications. SPRINT participants will be seen in clinics every few months at the beginning of the study and less frequently as their blood pressure is controlled. The study will include standard tests for determining the health of the heart, kidneys, and brain.
The clinical trial is based in large part on observational studies that suggest that maintaining a lower blood pressure level than is currently recommended reduces the risk of cardiovascular diseases.
High blood pressure is one of the most common conditions among middle-aged and older adults, and is a leading risk factor for stroke, heart disease, kidney failure, and other conditions. High blood pressure is also a key contributor to the development and progression of chronic kidney disease. SPRINT will examine the hypothesis that more aggressive blood pressure control will slow the development of chronic kidney disease beyond the benefit achieved by current blood pressure goals. Nearly 1 in 3 adult Americans has high blood pressure. Worldwide estimates suggest that over 900 million adults have high blood pressure.
"SPRINT is an important comparative effectiveness research study for a common and potentially costly condition. The combined expertise and resources of four institutes of the NIH maximizes our efforts to develop the scientific evidence to help patients and their doctors determine the best treatment options for them," stated NIH Director Francis S. Collins, M.D., Ph.D.
Blood pressure numbers are written with the systolic number above or before the diastolic number, such as 120/80 mmHg. Systolic pressure is the pressure on the arteries when the heart beats and pumps blood through the arteries, and diastolic pressure is the pressure when the heart is filling with blood between beats. Although systolic and diastolic measures are important, research has found that systolic pressure is a strong predictor of vascular problems caused by high blood pressure, especially among older individuals.
"To determine if a lower blood pressure goal reduces the risk of complications and death more than standard treatment to the current recommended goal level, we need evidence-based research. Only a large, long-term clinical trial comparing the two levels will give us the answer," said Elizabeth G. Nabel, M.D., director of the National Heart, Lung, and Blood Institute (NHLBI). "If this study shows that maintaining a lower systolic blood pressure has significant benefits for middle-aged and older adults - and doctors and patients meet the lower goal levels - we could see hundreds of thousands fewer heart attacks and stroke each year in the United States alone."
"On the other hand, if the results suggest no benefit from the lower goal level, then we will know that patients need not pursue more aggressive treatment than is currently recommended, which could save money and lower their risk of possible side effects from more intense treatment," added Nabel.
SPRINT is funded by the NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Two other NIH institutes - the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute on Aging (NIA) - will support SPRINT-MIND, a substudy that focuses on the impact of lowering systolic blood pressure to reduce cognitive impairment, an important early indication of dementia.
"Several observational studies suggest that elevated blood pressure could be an important factor leading to cognitive decline and dementia in older age," said NIA Director Richard J. Hodes, M.D. "SPRINT-MIND will provide important evidence of whether managing systolic blood pressure at lower levels can slow cognitive decline - an important consideration in light of the aging population."
Walter J. Koroshetz, M.D., NINDS deputy director, added, "It is critically important to know whether elderly persons with hypertensive cerebrovascular changes can tolerate such aggressive blood pressure lowering."
SPRINT will enroll approximately 7,500 participants age 55 years or older with systolic blood pressure of 130 mm Hg or higher. Participants will have a history of cardiovascular disease; be at high risk for heart disease by having at least one additional risk factor, such as smoking or high blood cholesterol levels; or have chronic kidney disease. Patients with a history of stroke or diabetes are not expected to be studied in SPRINT because other randomized clinical trials, such as the NINDS Stroke Prevention in Small Subcortical Stroke (known as SPS3) study and the NHLBI Action to Control Cardiovascular Risk in Diabetes (known as ACCORD) trial, are currently testing similar strategies in these patients. These studies will help inform how SPRINT is designed and conducted.
Enrollment for SPRINT is expected to begin in fall 2010. Participants will be randomly assigned to one of two groups: to treat systolic blood pressure to the lower goal of less than 120 mm Hg or to treat to the standard goal of less than 140 mm Hg. Participants will be followed for at least four years. Researchers will then compare the two groups to see if the participants in the lower blood pressure group had fewer heart attacks or strokes; were less likely to develop heart failure or chronic kidney disease; or had less decline in cognitive function. Deaths due to cardiovascular disease and quality-of-life measures will also be studied. In addition, a subgroup of participants will have moderate, or stage 3, kidney disease at enrollment; they will be studied to determine the impact of lower blood pressure on their risk of cardiovascular disease as well as end-stage kidney disease.
SPRINT tests the effectiveness of a medical strategy to reach specific blood pressure goals and does not compare specific drugs to each other. Study participants will be given specific blood-pressure lowering medications as determined by their research clinicians; medications may differ among participants in each treatment group.
"SPRINT will be a landmark study as it will be the first large randomized clinical trial to study how maintaining systolic blood pressure at a level lower than currently recommended will impact cardiovascular and kidney diseases, and cognitive decline in adults without diabetes or history of stroke," noted Lawrence J. Fine, M.D., Dr.P.H., chief of the Branch of Clinical Applications and Prevention and the SPRINT project officer at the NHLBI.
The clinical trial builds upon large, population-based studies that suggest that maintaining systolic blood pressure below 120 mm Hg may substantially lower the risk of cardiovascular diseases. Other observational studies suggest that high blood pressure is a risk factor for chronic kidney disease and dementia. In January 2007, a special ad hoc panel of scientific leaders in clinical high blood pressure research and clinical trials in cardiovascular disease convened by the NHLBI confirmed earlier recommendations that a clinical trial such as SPRINT is a top priority for cardiovascular research. According to a recent Cochrane review of scientific literature, no completed clinical trials have adequately tested the effects of the low systolic blood pressure target.
"Based on the results of other studies, the time is right for SPRINT," added Fine.
The study coordinating center is Wake Forest University in Winston-Salem, North Carolina (Principal investigator: David Reboussin, Ph.D).
The SPRINT study clinical center networks are:
- Case Western Reserve University School of Medicine, Cleveland, Ohio (Principal investigator: Jackson T. Wright, M.D., Ph.D.)
- Department of Veterans Affairs, VA Medical Center, Memphis, Tennessee (Principal investigator: William C. Cushman, M.D.)
- University of Alabama, Birmingham (Principal investigator: Suzanne Oparil, M.D.)
- University of Utah, Salt Lake City, Utah (Principal investigator: Alfred K. Cheung, M.D.)
- Wake Forest University, Winston-Salem, North Carolina (Principal investigator: David C. Goff, Jr., M.D., Ph.D.)
Study finds a subset of artificial heart patients can regenerate heart muscle