According to initial results of a landmark clinical trial released today at the National Institutes of Health, heart attacks, strokes, acute coronary syndrome, heart failure and death due to cardiovascular causes were reduced by almost one-third and risk of death was lowered by almost one-quarter in participants randomized to a systolic blood pressure goal of 120 mm Hg compared to those randomized to the usual goal of 140 mm Hg.
The NIH-sponsored the Systolic Blood Pressure Intervention Trial (SPRINT) enrolled more than 9,300 participants age 50 and older with high blood pressure. Participants were assigned at random to a systolic blood pressure target of 120 mm Hg or the usual target of 140 mm Hg, then had the amount and type of blood pressure medication adjusted to achieve the different blood pressure targets.
The groundbreaking results of this important trial, in which the University of Alabama at Birmingham and the UAB School of Medicine played major clinical and leadership roles, is expected to impact the way physicians across the United States and Puerto Rico treat patients with high blood pressure.
“SPRINT is a large, well designed and well conducted study, and is certain to influence the way clinicians manage the treatment of patients with high blood pressure and impact the decision making of future national guidelines committees,” said Suzanne Oparil, M.D., principal investigator for the UAB hub of the SPRINT trial, UAB professor of Medicine and director of the Vascular Biology and Hypertension Program in UAB’s School of Medicine. “While these results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall, patients should talk to their doctor to determine whether this lower goal is best for their individualized care.”
The SPRINT study, which began in the fall of 2009, recruited approximately 100 medical centers and clinical practices throughout the United States and Puerto Rico. UAB was selected by the NIH as one of five hubs to recruit and direct almost 20 of these clinics from Massachusetts to Puerto Rico; UAB-directed clinics recruited more than 1,950 study participants, surpassing the study’s initial goal for UAB’s network. The study’s blood pressure intervention, which was to finish in summer 2016, has finished earlier after the National Heart, Lung and Blood Institute Director Gary H. Gibbons, M.D., took action when the Data and Safety Monitoring Board interpreted the benefits of the lower goal as far outweighing the harms.
“This study provides potentially lifesaving information that will be useful to health care providers as they consider the best treatment options for some of their patients, particularly those over the age of 50,” Gibbons said. “We are delighted to have achieved this important milestone in the study in advance of the expected closure date for the SPRINT trial and look forward to quickly communicating the results to help inform patient care and the future development of evidence-based clinical guidelines.”
The SPRINT study is the largest of its kind to examine how maintaining systolic blood pressure at a lower than currently recommended level will impact cardiovascular and kidney diseases. More data in other areas will continue to be collected into 2016.
“Participants are still continuing in the trial to provide data on more end points and may continue on study drugs,” Oparil said. “SPRINT is a very large and important trial, however, the findings are still preliminary, and we will have to wait for the published paper for details.”
The NIH funded the SPRINT study in 2009 to answer one question: Will treating high blood pressure to a lower blood pressure goal — 120 mm Hg systolic compared to the traditional goal 140 mm Hg — reduce the risk of heart and kidney diseases, stroke, or age-related declines in memory and thinking?
High blood pressure is a leading cause of death and disability in the United States and worldwide. More than 60 percent of people over age 65 have high blood pressure, and the number of people with high blood pressure is increasing.
Experts in blood pressure management, primary care physicians, nephrologists or other health care providers have seen SPRINT participants regularly for a period of 4 to 6 years. UAB’s Vascular Biology and Hypertension Research Program Clinic, part of the UAB School of Medicine Division of Cardiovascular Disease and directed by professor of medicine David Calhoun, M.D., was one of several clinics that enrolled patients in Alabama. Athens Internal Medicine had the largest patient population in the study, with the more than 300 enrollees. The UAB Division of Nephrology and Nephrology Associates in Birmingham also participated and enrolled an important subgroup of patients with chronic kidney disease.
In additional to clinical roles, UAB faculty also have leadership roles in the SPRINT trial. Oparil and Cora E. Lewis, M.D., are on the trial-wide steering committee and co-lead the morbidity and mortality committee, in which capacity Oparil, Lewis and their committee members review medical records in order to determine whether trial participants have had a heart attack, heart failure, stroke or other cardiovascular event. Lewis also leads the measurement procedures and quality control committee and serves on the executive committee for the study.
Virginia Wadley Bradley, M.D., professor of medicine in the Division of Gerontology, Geriatrics and Palliative Care, is co-lead of the trial’s MIND committee, which oversees the cognitive and dementia aspects of the trial. Tom Ramsey, a program manager in Preventive Medicine, is the lead author of the trial’s recruitment paper, which is currently under review. Steve Glasser, M.D., professor of medicine in Preventive Medicine is a cardiologist who also is on the trial’s morbidity and mortality committee.
“UAB was selected and is able to be a part of this remarkable study because we put together a great team of investigators and staff to run the hub,” said Lewis, the co-principal investigator of the UAB hub. “We recruited a good diversity of clinics that could bring in diverse patients and achieve the study recruitment goals, we wrote an outstanding application, and we have a lot of relevant experience for all aspects of the trial. We are able to provide all of the logistical support and we have the infrastructure to handle a trial of this scope and magnitude. It was an incredibly competitive selection process.”
While investigators work to publish their cardiovascular results in the coming weeks, there are additional important questions from the trial that will be answered in 2016 after all of the data are collected, including:
- How are the 120 and 140 mm Hg benchmarks going to stack up relative to cognitive function and risks of dementia, especially in patients 75 or older?
- How will the benchmarks affect brain structure in addition to cognitive assessments?
- What do the two levels of blood pressure mean for hypertension as a cause of kidney disease, especially in African Americans?
“A lot of studies will exclude people who have chronic kidney disease, but we intentionally included them in the SPRINT trial,” Lewis said. “We want to know what these two levels will mean for kidney disease. It could be that a more aggressive way of treating hypertension would preserve kidney function, or it could be that after a certain age, the kidneys may need a little more blood pressure to adequately perfuse them — that is to get them an adequate blood supply. We really don’t know. It’s going to be incredible to get some answers to these and other questions.”
The study population was diverse and included women, racial/ethnic minorities, patients with established chronic kidney disease or cardiovascular disease, and the elderly. The investigators point out that the SPRINT study did not include patients with diabetes, prior stroke, or polycystic kidney disease, as other studies included those populations.
When SPRINT was designed, the well-established clinical guidelines recommended a systolic blood pressure of less than 140 mm Hg for healthy adults and less than 130 mm Hg for those with kidney disease or diabetes. Investigators designed SPRINT to determine the potential benefits of achieving systolic blood pressure of less than 120 mm Hg for hypertensive adults 50 years and older who are at risk for developing heart disease or kidney disease, or who already had heart or kidney disease and were at risk of disease progression.
Between 2010 and 2013, the SPRINT investigators randomly divided the study participants into two groups that differed according to targeted levels of blood pressure control. The standard group received blood pressure medications to achieve a target of less than 140 mm Hg. They received an average of two different blood pressure medications. The intensive treatment group received medications to achieve a target of less than 120 mm Hg and received an average of three medications.
“Our results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall,” said Lawrence Fine, M.D., chief, Clinical Applications and Prevention Branch at NHLBI. “But patients should talk to their doctor to determine whether this lower goal is best for their individual care.”
The study is also examining kidney disease, cognitive function, and dementia among the patients; however, those results are still under analysis and are not yet available, as additional information will be collected over the next year. The primary results of the trial will be published within the next few months.
In addition to primary sponsorship by the NHLBI, SPRINT is co-sponsored by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.