WASHINGTON, DC ( updated with commentary ) — A large study funded by the National Institutes of Health (NIH) has found that a more intensive strategy of lowering blood pressure—one that aims to achieve a systolic blood-pressure target of 120 mm Hg—reduces the risk of death and cardiovascular events when compared with a strategy that lowers systolic blood pressure to conventional targets[1].
In the Systolic Blood Pressure Intervention Trial (SPRINT), investigators report that treating high-risk hypertensive adults 50 years of age and older to a target of 120 mm Hg significantly reduced cardiovascular events by 30% and reduced all-cause mortality by nearly 25% when compared with patients treated to a target of 140 mm Hg.
"This study shows that intensive blood-pressure management can prevent the cardiovascular complications of hypertension and save lives," Dr Jackson Wright (Case Western Reserve University, Cleveland, OH), one of the SPRINT primary investigators, said during a media briefing announcing the top-line results.
The study, which included hypertensive patients with one additional cardiovascular risk factor or preexisting kidney disease, was stopped earlier than the planned 2018 completion date, given the benefit of the intensive strategy, according to investigators.
The SPRINT investigators did not disclose event rates or the absolute reduction in risk with any of the end points, including the primary composite end point of MI, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. During the media briefing, they said only that the reduction in the event rate was sufficiently large enough for the SPRINT data safety and monitoring board (DSMB) stop the trial early.
The SPRINT investigators said they plan to submit their findings to a medical journal for peer review and expect to see the paper published before the end of 2015.
Dr Sripal Bangalore (New York University School of Medicine, NY), who was not affiliated with the trial, said the past decade in hypertension has seen some "ups and downs" in terms of what the ideal blood-pressure target should be. "I think now we have a clear answer from a very large, robust study," he told heartwire from Medscape.
Bangalore stressed the importance of analyzing the full data set before making firm conclusions, but right now, given the clear reduction in cardiovascular complications and death, the findings from SPRINT are sure "to shake everything up."
Similarly, Dr Franz Messerli (St Luke's-Roosevelt Hospital, New York) told heartwire that "if the results are iron-clad, and since SPRINT was prematurely terminated, there is little doubt that they are, they will reduce some of our previous thoughts on the J-curve to hogwash."
Messerli said this does not mean that the J-curve—an inverse relationship between cardiovascular events and mortality at low blood pressures—has disappeared altogether, noting that a systolic blood pressure of zero will still result in death, but the "optimal on-treatment blood pressure is obviously lower than what was previously documented in many post hoc studies, including some of our own."
Finishing the SPRINT Faster Than ExpectedIn SPRINT, conducted across 100 clinical centers in the US and Puerto Rico, approximately 9300 patients were randomized to two treatment strategies. Dr Gary Gibbons, director of National, Heart, Lung, and Blood Institute (NHLBI), said SPRINT was conceived more than 10 years ago, and that while there is a consensus that treating high blood pressure reduces the risk of cardiovascular events, there remain uncertainties over just how much blood pressure should be lowered. He called the data from SPRINT "potentially lifesaving information."
SPRINT was designed as a target-based study, which gave physicians and patients flexibility in selecting antihypertensive medications to achieve the assigned degree of blood-pressure control. SPRINT investigators excluded patients with diabetes and those with a history of stroke. Approximately 25% of patients in the study were 75 years of age and older.
In the first treatment arm, patients were randomized to intensive blood-pressure control, the goal being a systolic blood pressure less than 120 mm Hg. In the intensive-therapy arm, patients were treated with three or more antihypertensive medications, including diuretics, such as chlorthalidone; the calcium-channel blocker amlodipine; and the ACE inhibitor lisinopril. These "evidence-based" drugs, said co–primary investigator Dr Suzanne Oparil (University of Alabama, Birmingham), have been shown in previous studies to not only lower blood pressure but also cardiovascular disease and mortality.
With the second strategy, patients were randomized to standard blood-pressure control, the aim of which was to achieve a target of less than 140 mm Hg. Patients were treated with an average of two antihypertensive medications.
The last patient visit was scheduled for 2016, but, as noted, the trial was stopped early, given the statistically significant 30% reduction in the primary composite end point and approximate 25% reduction in all-cause mortality, a secondary end point.
The SPRINT study also includes a substudy, known as SPRINT-MIND, which is currently ongoing and will assess whether the lower blood-pressure target reduces the incidence of dementia, slows the decline in cognitive function, and results in less cerebral small-vessel disease (assessed by MRI). The effects of treatment on kidney function are also still being evaluated.
What the Guidelines Say
Throughout the media briefing, the SPRINT investigators said it is too early to speculate on how the results will change clinical practice or alter the hypertension guidelines. They said the data still need to be analyzed by the SPRINT investigators and reviewed by other experts. Only once that happens will the data be "digested" by physicians and various guideline writing committees, said Wright. Once that process occurs, clinical recommendations based on SPRINT—namely, whether physicians should treat patients to a target of less than 120 mm Hg—can be made.
"I think it would be premature for us to make recommendations at this time," said Wright. "I will say, though, having said that, I am quite convinced all will be quite impressed when the SPRINT data are made available."
Still, the SPRINT investigators admitted the results are likely to shake up the management of patients with hypertension, especially given the controversies surrounding current guidelines.
Late in 2013, the Eighth Joint National Committee (JNC 8) released new guidelines on the management of adult hypertension, which contained departures from previous recommendations. The JNC 8 expert writing group, led by Dr Paul James (University of Iowa, Iowa City), relaxed the target blood-pressure and treatment-initiation thresholds in elderly patients and those younger than 60 years of age with diabetes and kidney disease.
For the patients 60 years of age and older, the JNC 8 guidelines recommend treating to a target of 150/90 mm Hg and to 140/90 mm Hg in everybody else. The relaxing of the targets, however, was not without controversy. In fact, five members of JNC 8 published a letter outlining their concerns with increasing the target systolic blood pressure target from 140 mm Hg to 150 mm Hg in patients 60 years of age and older.
Speaking during the briefing, Oparil acknowledged the current JNC 8 recommendations are contentious. While relaxing the target to less than 150 mm Hg caused consternation, Oparil said the SPRINT results are more than likely to challenge the conventional 140-mm-Hg target.
"This is a time of enlightenment," she said. "The NHLBI and other institutes have given us powerful new information."
To heartwire , Messerli said that given that SPRINT included patients 50 years of age and older, the 2013 JNC 8 decision to relax blood-pressure goals in those 60 years and older to less than 150 mm Hg appears to be wrong. "We merely hope that, unlike for the JNC 8, it will not take more than decade for a JNC 9 to digest these seminal findings before providing US physicians with evidence-based and clinically useful recommendations," he said.
Bangalore noted the inclusion criteria for entry in SPRINT would apply to a vast majority of US patients with hypertension, which will make the impressive results useful to physicians in practice.
The European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) guidelines state physicians should treat to a target of less than 140 mm Hg. The recommendation is a systolic blood pressure target between 140 to 150 mm Hg, but physicians can go lower than 140 mm Hg if the patient is fit and healthy, according to a document released in 2013.
In the Systolic Blood Pressure Intervention Trial (SPRINT), investigators report that treating high-risk hypertensive adults 50 years of age and older to a target of 120 mm Hg significantly reduced cardiovascular events by 30% and reduced all-cause mortality by nearly 25% when compared with patients treated to a target of 140 mm Hg.
"This study shows that intensive blood-pressure management can prevent the cardiovascular complications of hypertension and save lives," Dr Jackson Wright (Case Western Reserve University, Cleveland, OH), one of the SPRINT primary investigators, said during a media briefing announcing the top-line results.
The study, which included hypertensive patients with one additional cardiovascular risk factor or preexisting kidney disease, was stopped earlier than the planned 2018 completion date, given the benefit of the intensive strategy, according to investigators.
The SPRINT investigators did not disclose event rates or the absolute reduction in risk with any of the end points, including the primary composite end point of MI, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. During the media briefing, they said only that the reduction in the event rate was sufficiently large enough for the SPRINT data safety and monitoring board (DSMB) stop the trial early.
The SPRINT investigators said they plan to submit their findings to a medical journal for peer review and expect to see the paper published before the end of 2015.
Dr Sripal Bangalore (New York University School of Medicine, NY), who was not affiliated with the trial, said the past decade in hypertension has seen some "ups and downs" in terms of what the ideal blood-pressure target should be. "I think now we have a clear answer from a very large, robust study," he told heartwire from Medscape.
Bangalore stressed the importance of analyzing the full data set before making firm conclusions, but right now, given the clear reduction in cardiovascular complications and death, the findings from SPRINT are sure "to shake everything up."
Similarly, Dr Franz Messerli (St Luke's-Roosevelt Hospital, New York) told heartwire that "if the results are iron-clad, and since SPRINT was prematurely terminated, there is little doubt that they are, they will reduce some of our previous thoughts on the J-curve to hogwash."
Messerli said this does not mean that the J-curve—an inverse relationship between cardiovascular events and mortality at low blood pressures—has disappeared altogether, noting that a systolic blood pressure of zero will still result in death, but the "optimal on-treatment blood pressure is obviously lower than what was previously documented in many post hoc studies, including some of our own."
Finishing the SPRINT Faster Than ExpectedIn SPRINT, conducted across 100 clinical centers in the US and Puerto Rico, approximately 9300 patients were randomized to two treatment strategies. Dr Gary Gibbons, director of National, Heart, Lung, and Blood Institute (NHLBI), said SPRINT was conceived more than 10 years ago, and that while there is a consensus that treating high blood pressure reduces the risk of cardiovascular events, there remain uncertainties over just how much blood pressure should be lowered. He called the data from SPRINT "potentially lifesaving information."
SPRINT was designed as a target-based study, which gave physicians and patients flexibility in selecting antihypertensive medications to achieve the assigned degree of blood-pressure control. SPRINT investigators excluded patients with diabetes and those with a history of stroke. Approximately 25% of patients in the study were 75 years of age and older.
In the first treatment arm, patients were randomized to intensive blood-pressure control, the goal being a systolic blood pressure less than 120 mm Hg. In the intensive-therapy arm, patients were treated with three or more antihypertensive medications, including diuretics, such as chlorthalidone; the calcium-channel blocker amlodipine; and the ACE inhibitor lisinopril. These "evidence-based" drugs, said co–primary investigator Dr Suzanne Oparil (University of Alabama, Birmingham), have been shown in previous studies to not only lower blood pressure but also cardiovascular disease and mortality.
With the second strategy, patients were randomized to standard blood-pressure control, the aim of which was to achieve a target of less than 140 mm Hg. Patients were treated with an average of two antihypertensive medications.
The last patient visit was scheduled for 2016, but, as noted, the trial was stopped early, given the statistically significant 30% reduction in the primary composite end point and approximate 25% reduction in all-cause mortality, a secondary end point.
The SPRINT study also includes a substudy, known as SPRINT-MIND, which is currently ongoing and will assess whether the lower blood-pressure target reduces the incidence of dementia, slows the decline in cognitive function, and results in less cerebral small-vessel disease (assessed by MRI). The effects of treatment on kidney function are also still being evaluated.
What the Guidelines Say
Throughout the media briefing, the SPRINT investigators said it is too early to speculate on how the results will change clinical practice or alter the hypertension guidelines. They said the data still need to be analyzed by the SPRINT investigators and reviewed by other experts. Only once that happens will the data be "digested" by physicians and various guideline writing committees, said Wright. Once that process occurs, clinical recommendations based on SPRINT—namely, whether physicians should treat patients to a target of less than 120 mm Hg—can be made.
"I think it would be premature for us to make recommendations at this time," said Wright. "I will say, though, having said that, I am quite convinced all will be quite impressed when the SPRINT data are made available."
Still, the SPRINT investigators admitted the results are likely to shake up the management of patients with hypertension, especially given the controversies surrounding current guidelines.
Late in 2013, the Eighth Joint National Committee (JNC 8) released new guidelines on the management of adult hypertension, which contained departures from previous recommendations. The JNC 8 expert writing group, led by Dr Paul James (University of Iowa, Iowa City), relaxed the target blood-pressure and treatment-initiation thresholds in elderly patients and those younger than 60 years of age with diabetes and kidney disease.
For the patients 60 years of age and older, the JNC 8 guidelines recommend treating to a target of 150/90 mm Hg and to 140/90 mm Hg in everybody else. The relaxing of the targets, however, was not without controversy. In fact, five members of JNC 8 published a letter outlining their concerns with increasing the target systolic blood pressure target from 140 mm Hg to 150 mm Hg in patients 60 years of age and older.
Speaking during the briefing, Oparil acknowledged the current JNC 8 recommendations are contentious. While relaxing the target to less than 150 mm Hg caused consternation, Oparil said the SPRINT results are more than likely to challenge the conventional 140-mm-Hg target.
"This is a time of enlightenment," she said. "The NHLBI and other institutes have given us powerful new information."
To heartwire , Messerli said that given that SPRINT included patients 50 years of age and older, the 2013 JNC 8 decision to relax blood-pressure goals in those 60 years and older to less than 150 mm Hg appears to be wrong. "We merely hope that, unlike for the JNC 8, it will not take more than decade for a JNC 9 to digest these seminal findings before providing US physicians with evidence-based and clinically useful recommendations," he said.
Bangalore noted the inclusion criteria for entry in SPRINT would apply to a vast majority of US patients with hypertension, which will make the impressive results useful to physicians in practice.
The European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) guidelines state physicians should treat to a target of less than 140 mm Hg. The recommendation is a systolic blood pressure target between 140 to 150 mm Hg, but physicians can go lower than 140 mm Hg if the patient is fit and healthy, according to a document released in 2013.