ARTICLE IN BRIEF
The SPRINT study found a 25 percent reduction in rates of heart attack, heart failure, stroke, and death from heart disease among participants who aimed for a systolic blood pressure of 120 mm Hg, compared with those who achieved a blood pressure near the currently accepted target of 140 mm Hg. Experts assess the study's strengths and caveats.
While the results from a much-anticipated study show that reducing systolic blood pressure targets from 140 mm Hg to 120 mm Hg can prevent cardiovascular and cerebrovascular events and save lives, some experts caution against rushing to the assumption that lower blood pressure is better for everyone.
The Systolic Blood Pressure Intervention Trial, or SPRINT, followed more than 9,000 people for an average of 3.2 years. The investigators found a 25 percent reduction in rates of heart attack, heart failure, stroke, and death from heart disease among participants who aimed for a systolic blood pressure of 120 mm Hg, compared with those who achieved a systolic blood pressure near the currently accepted target of 140 mm Hg.
The study excluded people younger than age 50, people with diabetes, and those with a history of stroke — all factors that make it difficult to determine how applicable the findings are to those populations and whether a lower target should be widely adopted, experts said.
The tighter blood pressure control in the SPRINT study came with some complications. “Rates of serious adverse events of hypotension (p<0.001), syncope (p=0.003), electrolyte abnormalities (p=0.006), and acute kidney injury or failure (p<0.001), but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group,” the researchers reported. Many patients also had to take more medications to achieve the lower goal.
Nonetheless, the study turned up such compelling positive results that it was stopped early in September and some general findings were publicly released at that time. More complete results were presented in November at the American Heart Association (AHA) annual meeting in Orlando, FL, along with the publication of the data in the November 9 online edition of The New England Journal of Medicine (NEJM).
“Now that the data [are] out, it can be evaluated by providers and by guideline panels,” Jackson T. Wright Jr., MD, PhD, the first author of the study and a professor of medicine at Case Western Reserve University, told Neurology Today. “I think it is clear that there will need to be some new recommendations going forward.”
SPRINT, which was sponsored by various branches of the National Institutes of Health and conducted at 102 clinical sites in the United States, randomized 9,361 people to a systolic blood pressure target of 120 mm Hg or lower, or a target of 140 mm Hg or lower. The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.
Participants had to be at least 50 years old, have a systolic blood pressure of 130 to 180 mm Hg, and have an increased risk for cardiovascular events based on their medical profile; people with diabetes, chronic kidney disease, or history of stroke were excluded.
At one year, the intensive treatment group had reached a mean systolic blood pressure of 121.4 mm Hg, compared with 136.2 mm Hg for the standard treatment group.
The study was designed to include a follow-up of up to six years, but it was halted at a median follow-up of 3.26 years when the safety monitoring board saw that the results were trending heavily in favor of patients with the lower blood pressure.
Among the findings, the researchers reported that the rate of cardiovascular events or death was 1.65 percent per year for people in the intensive treatment group versus 2.19 percent for the standard therapy group (p<0.001), which translated into a 25 percent relative lower risk. The intensive treatment group also had a 27 percent lower relative risk for all-cause death (p=0.003) and an 11 percent lower relative risk for stroke, but the stroke result was not statistically significant.
Serious adverse events likely due to the intervention such as hypotension, syncope, and kidney failure occurred in 4.7 percent of those in the intensive treatment group and in 2.5 percent of those in the standard treatment group.
More medication was needed to achieve the lower blood pressure target. Patients in the intensive treatment group took on average 2.8 blood pressure medications, compared with 1.8 medications in the standard therapy group.
“The trial indicates that we can get people down to the target we set in the study,” Dr. Wright said. “The challenge is that this will require more medication, better management of patients, and likely more attention paid to the lifestyle changes we've been advocating for decades.”
Dr. Wright said he and the other SPRINT researchers are continuing to analyze the data to look more closely at the risk for kidney damage and failure, and to determine whether rates of dementia and other forms of cognitive impairment differed between the two groups. The investigators conducted cognitive assessments and MRI scans in a subgroup of SPRINT participants, but those results have not yet been published.
In several editorials accompanying the SPRINT data, experts said they were encouraged by the findings, but cautioned that that it would take more time to assess the results, compare them to previous studies, and determine whether there should be any change in how doctors manage blood pressure.
There is currently no consensus on how low blood pressure should be, and even professional groups that issue guidelines are not consistent, having tightened or loosened their recommendations at different points in time.
A joint scientific statement from American Heart Association and the American College of Cardiology earlier this year set blood pressure recommendations for persons at high risk for cardiovascular disease at 140/90. Last year, a federal panel known JNC-8 (for the eighth annual Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) raised its systolic blood pressure target recommendation for persons over the age of 60 to less than 150. Those younger than 60 were advised to stay with the systolic target of less than 140.
Cheryl Bushnell, MD, a professor of neurology and director of the Comprehensive Stroke Center at Wake Forest Baptist Medical Center, said there was a flurry of excitement and discussion surrounding the interpretation of the SPRINT findings at the American Heart Association meeting, especially in light of data from other trials. She noted, for example, that data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which included nearly 5,000 people with type 2 diabetes, did not find a cardiovascular advantage to maintaining systolic blood pressure of 120 rather than 140 for the composite outcome. [See data from both trials in the table “Outcomes Data from SPRINT and ACCORD and Combined Data from Both Trials.”]
The ACCORD results, which were published in the NEJM in 2010, did find that the lower blood pressure goal reduced stroke risk, however.
Dr. Bushnell, who was vice chair for the committee that wrote the current primary stroke prevention guidelines for the AHA/ASA, said the SPRINT results leave open to debate the question of whether a systolic blood pressure target of 120 would reduce cardiovascular risk for patients with a history of stroke. With regard to recurring ischemic stroke, Dr. Bushnell noted that a trial conducted in patients who had had a lacunar stroke showed no advantage to achieving a target of 130 compared with 150. It would be useful to conduct a randomized trial similar to SPRINT involving all types of stroke patients, she said.
No matter what guidelines say, physicians must manage a patient's blood pressure based on an individual assessment of that person's cardiovascular risk and overall health, keeping in mind that “there are non-pharmacologic ways to lower blood pressure,” Dr. Bushnell said.
Clifford B. Saper, MD, PhD, FAAN, the James Jackson Putnam professor of neurology and neuroscience at Harvard Medical School, who wrote an editorial on the study in the Annals of Neurology in November, said previously published findings already suggest that “a lower pressure may be too aggressive for some people, and you have to be a little more careful.” Clinicians need to consider that too-low blood pressure can cause cerebral hypofusion, which can cause ischemic brain damage and cognitive impairment. This is especially a concern with older patients, he said.
Dr. Saper urged clinicians not to focus singularly on the systolic blood pressure number, but rather to consider the mean arterial pressure, or MAP (MAP=2/3 diastolic BP+1/3 systolic BP), which is an indicator of whether a patient is maintaining the blood pressure needed for adequate blood flow to the brain. In general, a MAP of about 60 is sufficient to support cerebral blood flow in a healthy young person, but in an elderly person whose blood pressure has been running high (for example, 140/90), a MAP of 70 to 80 may be necessary to perfuse the brain, he said. Dr. Saper also emphasized that blood pressure should be taken, and the patient questioned about symptoms, when he or she is in a standing position.
Neurologists need to be attentive to the possibility that patients who come in with complaints of confusion, dizziness, forgetfulness, or a sense of feeling “foggy” may be experiencing the consequences of too-tight blood pressure management by their primary care physician, he added.
“What worries me is that physicians will see this paper appearing in the New England Journal of Medicine and just go ahead and start lowering their patients' blood pressure,” without considering the potential risks, Dr. Saper said.
James F. Meschia, MD, FAAN, a professor and chair of neurology at the Mayo Clinic in Jacksonville, FL, who chaired the committee that wrote the 2014 AHA/ASA guidelines for primary prevention of stroke, said “the SPRINT trial fairly convincingly shows that aiming for a more aggressive target is appropriate.”
But before any blood pressure guidelines are revised, there needs to be careful consideration of SPRINT in the context of evidence that has emerged from other trials, he said. The neurocognitive findings from the trial, which have not yet been published, will be important to any guideline discussions, he noted.
In the meantime, doctors may decide to become more proactive on their own. “I think you're going to see in doctor's offices a more aggressive posture with regard to blood pressure. If someone is in the 130 to 150 range, physicians, barring no reason not to, will add another blood pressure drug,” Dr. Meschia said.
The problem is that physicians could definitely go too far. “We don't want to take an extremist position. Control of blood pressure has to be considered as part of the overall package of optimizing cardiovascular health,” along with weight control, exercise, diet, and smoking cessation.
SPRINT may leave the impression that lowering and maintaining blood pressure in the 120 mm Hg range is easily accomplished, Dr. Meschia said. But in fact “it requires a lot of work on both the part of the patient and the health care system to achieve these goals.”
EXPERTS: ON SPRINT OUTCOMES AND LOWERING SYSTOLIC BLOOD PRESSURE TARGETS