Intensive Blood Pressure Treatment May Be Beneficial

For people at high risk of cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, compared with a target of less than 140 mm Hg, may reduce the risk of fatal and nonfatal major cardiovascular events and death from any cause, according to research published online ahead of print November 9 in New England Journal of Medicine. The lower systolic blood pressure target may not significantly reduce the risk of stroke, however, compared with the higher target. The lower target also may increase patients’ risk of adverse events.

The research “provides evidence of benefits for an even lower systolic blood pressure target than that currently recommended in most patients with hypertension,” said Jackson T. Wright Jr., MD, PhD, Program Director of the William T. Dahms Clinical Research Unit at University Hospitals Case Medical Center in Cleveland. Approximately half of Americans control their blood pressure to a level less than 140/90 mm Hg, which may be a challenging target. “Achieving a systolic blood pressure goal of less than 120 mm Hg in the overall population of patients with hypertension would be more demanding and time-consuming for both providers and patients than achieving a goal of 140 mm Hg, and would necessitate increased medication costs and clinic visits,” said Dr. Wright.

The SPRINT Study

The appropriate systolic blood pressure target for people without diabetes is uncertain. Randomized controlled trials including patients with hypertension indicate the benefit of treatment to achieve a systolic blood pressure target of less than 150 mm Hg, but data about lower blood pressure targets are limited. In the Systolic Blood Pressure Intervention Trial (SPRINT), Dr. Wright and colleagues compared the benefit of treatment of systolic blood pressure to a target of less than 120 mm Hg with that of treatment to a target of less than 140 mm Hg.

The investigators conducted SPRINT, a randomized, controlled, open-label trial, at 102 clinical sites in the United States, including Puerto Rico. Eligible participants were age 50 or older, had a systolic blood pressure of 130 to 180 mm Hg, and had an increased risk of cardiovascular events. Increased cardiovascular risk was defined by one or more of the following factors: clinical or subclinical cardiovascular disease other than stroke, chronic kidney disease, a 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score, or an age of 75 or older. Researchers excluded people with diabetes or prior stroke.

Participants were assigned to a systolic blood pressure target of either less than 140 mm Hg (ie, the standard-treatment group) or less than 120 mm Hg (ie, the intensive-treatment group). Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not. Participants’ antihypertensive regimens were adjusted according to their study-group assignments. All major classes of antihypertensive agents were included in the formulary and were provided free to the participants. The investigators also encouraged lifestyle modification. Participants were seen monthly for the first three months and every three months thereafter.

The primary outcome was the composite outcome of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Secondary outcomes included the individual elements of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.

Intensive Treatment Reduced Mortality

A total of 9,361 participants were enrolled in SPRINT. The trial was stopped early after analyses of the primary outcome exceeded the monitoring boundary at two consecutive time points. Median follow-up was 3.26 years of the planned average of five years.

At one year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The average difference between groups was 14.8 mm Hg. The mean diastolic blood pressure at one year was 68.7 mm Hg in the intensive-treatment group and 76.3 mm Hg in the standard-treatment group. The mean number of blood pressure medications was 2.8 in the intensive-treatment group and 1.8 in the standard-treatment group.

A total of 243 patients (1.65% per year) in the intensive-treatment group and 319 patients (2.19% per year) in the standard-treatment group had a primary outcome event. The hazard ratio for these events was 0.75 in the intensive-treatment group. The between-group differences were consistent for all components of the primary outcome and other prespecified secondary outcomes. In all, 365 deaths occurred—155 in the intensive-treatment group and 210 in the standard-treatment group. The relative risk of death from cardiovascular causes was 43% lower with the intensive intervention than with the standard treatment.

In all, 1,793 participants in the intensive-treatment group (38.3%) and 1,736 participants in the standard-treatment group (37.1%) had a serious adverse event. The hazard ratio of serious adverse events was 1.04 for the intensive-treatment group. Events such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure were more common in the intensive-treatment group than in the standard-treatment group. Orthostatic hypotension was significantly less common in the intensive-treatment group.

The intensive-treatment group in SPRINT had a nonsignificant 11% lower incidence of stroke. For comparison, treatment to an intensive systolic blood pressure goal of less than 130 mm Hg was associated with a nonsignificant 19% lower incidence of stroke in the Secondary Prevention of Small Subcortical Strokes trial, compared with treatment to higher targets. Treatment to an intensive systolic blood pressure goal of less than 120 mm Hg was associated with a significant 41% lower incidence of stroke in the ACCORD trial.

“Among adults with hypertension but without diabetes, lowering systolic blood pressure to a target goal of less than 120 mm Hg, as compared with the standard goal of less than 140 mm Hg, resulted in significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause,” said Dr. Wright.

Ramifications for Future Guidelines

“A goal for systolic blood pressure of less than 150 mm Hg now seems too high for most elderly patients, and a more aggressive approach appears warranted for those with cardiovascular disease or at high risk for it,” said Aram V. Chobanian, MD, Professor of Medicine at Boston University School of Medicine, in an accompanying editorial. A goal for systolic blood pressure of less than 120 mm Hg may be inappropriate for most people with hypertension, however, because many participants in the SPRINT intensive-treatment group did not reach their target blood pressure, he added. “The results from SPRINT warrant reducing the treatment goal for systolic blood pressure to less than 130 mm Hg in most people with hypertension who are over 50 years of age and do not have diabetes or a history of stroke.”

Reaching stricter blood pressure goals likely will require more careful titration of medications, greater use of combination drug preparations, more monitoring for adverse effects, and more frequent patient visits, said Dr. Chobanian.

An analysis published online ahead of print November 9 in Journal of the American College of Cardiology found that if guidelines were to be based on the SPRINT results, more than 16.8 million Americans could be recommended for intensive blood pressure management. African Americans and Hispanics are less likely to meet SPRINT eligibility criteria, compared with Caucasians, largely because the minority populations have a higher prevalence of diabetes and other health conditions. Men are more likely to meet SPRINT eligibility criteria than women, partly because women tend not to have increased risk for cardiovascular disease until they are older than 65.

—Erik Greb

For people at high risk of cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, compared with a target of less than 140 mm Hg, may reduce the risk of fatal and nonfatal major cardiovascular events and death from any cause, according to research published online ahead of print November 9 in New England Journal of Medicine. The lower systolic blood pressure target may not significantly reduce the risk of stroke, however, compared with the higher target. The lower target also may increase patients’ risk of adverse events.

The research “provides evidence of benefits for an even lower systolic blood pressure target than that currently recommended in most patients with hypertension,” said Jackson T. Wright Jr., MD, PhD, Program Director of the William T. Dahms Clinical Research Unit at University Hospitals Case Medical Center in Cleveland. Approximately half of Americans control their blood pressure to a level less than 140/90 mm Hg, which may be a challenging target. “Achieving a systolic blood pressure goal of less than 120 mm Hg in the overall population of patients with hypertension would be more demanding and time-consuming for both providers and patients than achieving a goal of 140 mm Hg, and would necessitate increased medication costs and clinic visits,” said Dr. Wright.

The SPRINT Study

The appropriate systolic blood pressure target for people without diabetes is uncertain. Randomized controlled trials including patients with hypertension indicate the benefit of treatment to achieve a systolic blood pressure target of less than 150 mm Hg, but data about lower blood pressure targets are limited. In the Systolic Blood Pressure Intervention Trial (SPRINT), Dr. Wright and colleagues compared the benefit of treatment of systolic blood pressure to a target of less than 120 mm Hg with that of treatment to a target of less than 140 mm Hg.

The investigators conducted SPRINT, a randomized, controlled, open-label trial, at 102 clinical sites in the United States, including Puerto Rico. Eligible participants were age 50 or older, had a systolic blood pressure of 130 to 180 mm Hg, and had an increased risk of cardiovascular events. Increased cardiovascular risk was defined by one or more of the following factors: clinical or subclinical cardiovascular disease other than stroke, chronic kidney disease, a 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score, or an age of 75 or older. Researchers excluded people with diabetes or prior stroke.

Participants were assigned to a systolic blood pressure target of either less than 140 mm Hg (ie, the standard-treatment group) or less than 120 mm Hg (ie, the intensive-treatment group). Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not. Participants’ antihypertensive regimens were adjusted according to their study-group assignments. All major classes of antihypertensive agents were included in the formulary and were provided free to the participants. The investigators also encouraged lifestyle modification. Participants were seen monthly for the first three months and every three months thereafter.

The primary outcome was the composite outcome of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Secondary outcomes included the individual elements of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.

Intensive Treatment Reduced Mortality

A total of 9,361 participants were enrolled in SPRINT. The trial was stopped early after analyses of the primary outcome exceeded the monitoring boundary at two consecutive time points. Median follow-up was 3.26 years of the planned average of five years.

At one year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The average difference between groups was 14.8 mm Hg. The mean diastolic blood pressure at one year was 68.7 mm Hg in the intensive-treatment group and 76.3 mm Hg in the standard-treatment group. The mean number of blood pressure medications was 2.8 in the intensive-treatment group and 1.8 in the standard-treatment group.

A total of 243 patients (1.65% per year) in the intensive-treatment group and 319 patients (2.19% per year) in the standard-treatment group had a primary outcome event. The hazard ratio for these events was 0.75 in the intensive-treatment group. The between-group differences were consistent for all components of the primary outcome and other prespecified secondary outcomes. In all, 365 deaths occurred—155 in the intensive-treatment group and 210 in the standard-treatment group. The relative risk of death from cardiovascular causes was 43% lower with the intensive intervention than with the standard treatment.

In all, 1,793 participants in the intensive-treatment group (38.3%) and 1,736 participants in the standard-treatment group (37.1%) had a serious adverse event. The hazard ratio of serious adverse events was 1.04 for the intensive-treatment group. Events such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure were more common in the intensive-treatment group than in the standard-treatment group. Orthostatic hypotension was significantly less common in the intensive-treatment group.

The intensive-treatment group in SPRINT had a nonsignificant 11% lower incidence of stroke. For comparison, treatment to an intensive systolic blood pressure goal of less than 130 mm Hg was associated with a nonsignificant 19% lower incidence of stroke in the Secondary Prevention of Small Subcortical Strokes trial, compared with treatment to higher targets. Treatment to an intensive systolic blood pressure goal of less than 120 mm Hg was associated with a significant 41% lower incidence of stroke in the ACCORD trial.

“Among adults with hypertension but without diabetes, lowering systolic blood pressure to a target goal of less than 120 mm Hg, as compared with the standard goal of less than 140 mm Hg, resulted in significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause,” said Dr. Wright.

Ramifications for Future Guidelines

“A goal for systolic blood pressure of less than 150 mm Hg now seems too high for most elderly patients, and a more aggressive approach appears warranted for those with cardiovascular disease or at high risk for it,” said Aram V. Chobanian, MD, Professor of Medicine at Boston University School of Medicine, in an accompanying editorial. A goal for systolic blood pressure of less than 120 mm Hg may be inappropriate for most people with hypertension, however, because many participants in the SPRINT intensive-treatment group did not reach their target blood pressure, he added. “The results from SPRINT warrant reducing the treatment goal for systolic blood pressure to less than 130 mm Hg in most people with hypertension who are over 50 years of age and do not have diabetes or a history of stroke.”

Reaching stricter blood pressure goals likely will require more careful titration of medications, greater use of combination drug preparations, more monitoring for adverse effects, and more frequent patient visits, said Dr. Chobanian.

An analysis published online ahead of print November 9 in Journal of the American College of Cardiology found that if guidelines were to be based on the SPRINT results, more than 16.8 million Americans could be recommended for intensive blood pressure management. African Americans and Hispanics are less likely to meet SPRINT eligibility criteria, compared with Caucasians, largely because the minority populations have a higher prevalence of diabetes and other health conditions. Men are more likely to meet SPRINT eligibility criteria than women, partly because women tend not to have increased risk for cardiovascular disease until they are older than 65.

—Erik Greb

For people at high risk of cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, compared with a target of less than 140 mm Hg, may reduce the risk of fatal and nonfatal major cardiovascular events and death from any cause, according to research published online ahead of print November 9 in New England Journal of Medicine. The lower systolic blood pressure target may not significantly reduce the risk of stroke, however, compared with the higher target. The lower target also may increase patients’ risk of adverse events.

The research “provides evidence of benefits for an even lower systolic blood pressure target than that currently recommended in most patients with hypertension,” said Jackson T. Wright Jr., MD, PhD, Program Director of the William T. Dahms Clinical Research Unit at University Hospitals Case Medical Center in Cleveland. Approximately half of Americans control their blood pressure to a level less than 140/90 mm Hg, which may be a challenging target. “Achieving a systolic blood pressure goal of less than 120 mm Hg in the overall population of patients with hypertension would be more demanding and time-consuming for both providers and patients than achieving a goal of 140 mm Hg, and would necessitate increased medication costs and clinic visits,” said Dr. Wright.

The SPRINT Study

The appropriate systolic blood pressure target for people without diabetes is uncertain. Randomized controlled trials including patients with hypertension indicate the benefit of treatment to achieve a systolic blood pressure target of less than 150 mm Hg, but data about lower blood pressure targets are limited. In the Systolic Blood Pressure Intervention Trial (SPRINT), Dr. Wright and colleagues compared the benefit of treatment of systolic blood pressure to a target of less than 120 mm Hg with that of treatment to a target of less than 140 mm Hg.

The investigators conducted SPRINT, a randomized, controlled, open-label trial, at 102 clinical sites in the United States, including Puerto Rico. Eligible participants were age 50 or older, had a systolic blood pressure of 130 to 180 mm Hg, and had an increased risk of cardiovascular events. Increased cardiovascular risk was defined by one or more of the following factors: clinical or subclinical cardiovascular disease other than stroke, chronic kidney disease, a 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score, or an age of 75 or older. Researchers excluded people with diabetes or prior stroke.

Participants were assigned to a systolic blood pressure target of either less than 140 mm Hg (ie, the standard-treatment group) or less than 120 mm Hg (ie, the intensive-treatment group). Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not. Participants’ antihypertensive regimens were adjusted according to their study-group assignments. All major classes of antihypertensive agents were included in the formulary and were provided free to the participants. The investigators also encouraged lifestyle modification. Participants were seen monthly for the first three months and every three months thereafter.

The primary outcome was the composite outcome of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Secondary outcomes included the individual elements of the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause.

Intensive Treatment Reduced Mortality

A total of 9,361 participants were enrolled in SPRINT. The trial was stopped early after analyses of the primary outcome exceeded the monitoring boundary at two consecutive time points. Median follow-up was 3.26 years of the planned average of five years.

At one year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The average difference between groups was 14.8 mm Hg. The mean diastolic blood pressure at one year was 68.7 mm Hg in the intensive-treatment group and 76.3 mm Hg in the standard-treatment group. The mean number of blood pressure medications was 2.8 in the intensive-treatment group and 1.8 in the standard-treatment group.

A total of 243 patients (1.65% per year) in the intensive-treatment group and 319 patients (2.19% per year) in the standard-treatment group had a primary outcome event. The hazard ratio for these events was 0.75 in the intensive-treatment group. The between-group differences were consistent for all components of the primary outcome and other prespecified secondary outcomes. In all, 365 deaths occurred—155 in the intensive-treatment group and 210 in the standard-treatment group. The relative risk of death from cardiovascular causes was 43% lower with the intensive intervention than with the standard treatment.

In all, 1,793 participants in the intensive-treatment group (38.3%) and 1,736 participants in the standard-treatment group (37.1%) had a serious adverse event. The hazard ratio of serious adverse events was 1.04 for the intensive-treatment group. Events such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure were more common in the intensive-treatment group than in the standard-treatment group. Orthostatic hypotension was significantly less common in the intensive-treatment group.

The intensive-treatment group in SPRINT had a nonsignificant 11% lower incidence of stroke. For comparison, treatment to an intensive systolic blood pressure goal of less than 130 mm Hg was associated with a nonsignificant 19% lower incidence of stroke in the Secondary Prevention of Small Subcortical Strokes trial, compared with treatment to higher targets. Treatment to an intensive systolic blood pressure goal of less than 120 mm Hg was associated with a significant 41% lower incidence of stroke in the ACCORD trial.

“Among adults with hypertension but without diabetes, lowering systolic blood pressure to a target goal of less than 120 mm Hg, as compared with the standard goal of less than 140 mm Hg, resulted in significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause,” said Dr. Wright.

Ramifications for Future Guidelines

“A goal for systolic blood pressure of less than 150 mm Hg now seems too high for most elderly patients, and a more aggressive approach appears warranted for those with cardiovascular disease or at high risk for it,” said Aram V. Chobanian, MD, Professor of Medicine at Boston University School of Medicine, in an accompanying editorial. A goal for systolic blood pressure of less than 120 mm Hg may be inappropriate for most people with hypertension, however, because many participants in the SPRINT intensive-treatment group did not reach their target blood pressure, he added. “The results from SPRINT warrant reducing the treatment goal for systolic blood pressure to less than 130 mm Hg in most people with hypertension who are over 50 years of age and do not have diabetes or a history of stroke.”

Reaching stricter blood pressure goals likely will require more careful titration of medications, greater use of combination drug preparations, more monitoring for adverse effects, and more frequent patient visits, said Dr. Chobanian.

An analysis published online ahead of print November 9 in Journal of the American College of Cardiology found that if guidelines were to be based on the SPRINT results, more than 16.8 million Americans could be recommended for intensive blood pressure management. African Americans and Hispanics are less likely to meet SPRINT eligibility criteria, compared with Caucasians, largely because the minority populations have a higher prevalence of diabetes and other health conditions. Men are more likely to meet SPRINT eligibility criteria than women, partly because women tend not to have increased risk for cardiovascular disease until they are older than 65.

—Erik Greb