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Study Overview
Objective. To determine the effects of intensive (≤ 120 mm Hg) compared with standard (< 140 mm Hg) systolic blood pressure (SBP) targets in adults aged 75 years and older with hypertension.
Design. Randomized controlled trial.
Setting and participants. Participants were a pre-specified subgroup of adults aged 75 years and older from the Systolic Blood Pressure Intervention Trial (SPRINT), an open-label trial conducted at 102 clinical sites in the United States [1]. Participants were included if they had a systolic blood pressure of 130–180 mm Hg and were at increased risk for cardiovascular disease, based on a history of clinical or subclinical cardiovascular disease, chronic kidney disease, or a 10-year Framingham general cardiovascular disease risk score ≥ 15%. Adults with type 2 diabetes, a history of stroke, symptomatic heart failure within the previous 6 months or reduced left ventricular ejection fraction of less than 35%, a clinical diagnosis of dementia, an expected survival of less than 3 years, unintentional weight loss greater than 10% of body weight in the previous 5 months, a systolic blood pressure < 110 mm Hg following 1 minute of standing, or residing in a nursing home were excluded.
Intervention. Participants were randomized to SBP targets of ≤ 120 mm Hg (intensive treatment group) or SBP targets of < 140 mm Hg (standard treatment group). After randomization, the baseline antihypertensive regimens were adjusted according to treatment algorithms used in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial [2]. All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. Investigators could also prescribe other antihypertensive medications, which were not provided by the study. The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes. Participants were seen monthly for the first 3 months and then every 3 months thereafter for measurement of their blood pressure to adjust medications to target SBP. The length of follow-up period was planned to be an average of 5 years.
Main outcome measures. The primary study outcome was a composite of non-fatal myocardial infarction, acute coronary syndrome, non-fatal stroke, non-fatal acute decompensated heart failure, and death from cardiovascular causes. Secondary outcomes included all-cause mortality and the composite of primary study outcomes and all-cause mortality. Study outcomes were adjudicated by investigators unaware of study group assignments. Because it is not clear from previous literature if the treatment effect may be modified by the frailty status of the study participants, the study included in its baseline measurements for participants frailty status and an exploratory analysis to examine if the treatment effect varied by frailty status.
Main results. Average age of participants was 80 years, 62% were men, and the baseline systolic blood pressure was 142 mm Hg on average. Overall 31% of participants were classified as frail. The mean SBP achieved in the intensive treatment group was 123 mm Hg during follow-up, and the mean SBP in the standard treatment group was 135 mm Hg. Participants in the intensive treatment group received on average 1 more medication to reach lower SBP. Participants in the intensive group had a lower incidence of the primary outcome, 2.59% per year compared to 3.85% per year in the standard treatment group with a hazard ratio of 0.66 (95% CI, 0.51–0.85). At 3.14 years, the number needed to treat (NNT) for the primary outcome was 27. For all-cause mortality, the intensive treatment group also had lower rates: 73 deaths compared to 107 deaths in the standard treatment group (NNT, 41). In the exploratory analysis, frailty status did not significantly modify the effect of intensive treatment (P = 0.84 for interaction). The rate of adverse events in the intensive treatment group was not statistically significantly different from the standard treatment group; the rate of orthostatic hypotension was also not different between the groups.
Conclusion. Treatment of hypertension to an SBP target of ≤ 120 mm Hg compared with an SBP target of < 140 mm Hg led to lower rates of cardiovascular events and mortality among ambulatory older adults aged 75 and older.
Commentary
Published in 2012, the largest randomized controlled trial on the treatment of hypertension in older adults—the Hypertension in the Very Elderly Trial (HYVET)—found that treatment of older adults aged 80 and older with an SBP of 160 mm Hg with a target of < 150 mm Hg led to a reduction in cardiovascular deaths, strokes, and death from any cause [3]. The current SPRINT study went a step further by lowering the target SBP to 120 mm Hg and found that when compared to a target of < 140 mm Hg, the more intensive control also yielded significant benefits in reducing rates of cardiovascular events and mortality among older adults. Although average SBP reached in the intensive group was higher than the targeted goal of 120 mm Hg (an average of 123 mm Hg during follow-up), it demonstrated the clinical benefits of reducing SBP by over 10 mm Hg when compared with standard treatment group by adding on average 1 antihypertensive medication. The study did not directly tackle the issue of diastolic blood pressure (DBP) levels, though noting that treatment goal should lower DBP to < 90 mm Hg. The intensive treatment group also did not have significantly higher rates of adverse events including orthostatic hypotension and injurious falls, alleviating some of the concerns of clinicians when considering intensifying treatment of hypertension in older adults.
Clinicians often hesitate to intensify hypertension treatment among older adults because previously there has been a lack of evidence that demonstrated conclusively that lowering blood pressure yields clinical benefits [4]. The older adult population is often underrepresented in previous trials of hypertension, and prior observational studies often failed to demonstrate that lower blood pressures associate with better clinical outcomes [5]. Coupled with the concern for the high prevalence of white coat hypertension, orthostatic hypotension, falls, and frailty in the older adult population, clinicians are often concerned that intensifying hypertension treatment may do more harm than good [4]. The current study took great care in tackling some of these issues by including a measurement of frailty, by allowing older adults with postural changes in blood pressure to be included (except for those with standing blood pressure in very low range of < 110 mm Hg), and by tracking adverse events including orthostatic hypotension and injurious falls. The results should help to provide the evidence to convince clinicians that there is substantial value in intensifying hypertension treatment among ambulatory older adults and dispel some of the concerns that clinicians may have regarding its potential harms. Of note, the study excluded older adults that perhaps represent the frailest group of the older adult population—those living in nursing homes, those with dementia, and those with life expectancy of less than 3 years. The study results should not extrapolate to these groups. The analysis examining if treatment effect is consistent among those who are frail should be considered exploratory in nature, as pointed out by the study authors and the editorial to the article [6]. Further studies are needed to examine this issue.
Applications for Clinical Practice
The current study provides strong evidence that intensifying antihypertensive treatment to SBP in the range of 120 mm Hg confers clinical benefits to older ambulatory adults aged 75 and older. The current guidelines published by the Eighth Joint National Committee (JNC 8) recommends that treatment in the general population aged ≥ 60 years should consist of initiating pharmacologic treatment at SBP ≥ 150 mm Hg and treat to a goal SBP < 150 mm Hg [7]. Given the findings from the current study, the guidelines should be revised to reflect the new evidence generated from the current study. Although cardiovascular events and mortality are important clinical outcomes, other outcomes important to the older adult population should also be examined such as quality of life and functional outcomes. The SPRINT study did include these outcomes in its protocol and we look forward to additional insights regarding treatment impact on these important outcomes.
—William W. Hung, MD, MPH
1. Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive vs standard blood pressure control. N Engl J Med 2015;373:2103–16.
2. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85.
3. Beckett N, Peters R, Tuomilehto J et al. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial. BMJ 2011;344:d7541.
4. Morley JE. Systolic hypertension should not be treated in persons aged 80 and older until blood pressure is greater than 160 mmHg. J Am Geriatr Soc 2013;61:1197–8.
5. Jacobs JM, Stessman J, Ein-Mor E, et al. Hypertension and 5-year mortality among 85-year-olds: The Jerusalem Longitudinal Study. J Am Med Dir Assoc 2012;13:759.e1–759.e6.
6. Chobanian AV. SPRINT results in older patients: How low to go? JAMA 2016;315:2669–70.
7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20.
Study Overview
Objective. To determine the effects of intensive (≤ 120 mm Hg) compared with standard (< 140 mm Hg) systolic blood pressure (SBP) targets in adults aged 75 years and older with hypertension.
Design. Randomized controlled trial.
Setting and participants. Participants were a pre-specified subgroup of adults aged 75 years and older from the Systolic Blood Pressure Intervention Trial (SPRINT), an open-label trial conducted at 102 clinical sites in the United States [1]. Participants were included if they had a systolic blood pressure of 130–180 mm Hg and were at increased risk for cardiovascular disease, based on a history of clinical or subclinical cardiovascular disease, chronic kidney disease, or a 10-year Framingham general cardiovascular disease risk score ≥ 15%. Adults with type 2 diabetes, a history of stroke, symptomatic heart failure within the previous 6 months or reduced left ventricular ejection fraction of less than 35%, a clinical diagnosis of dementia, an expected survival of less than 3 years, unintentional weight loss greater than 10% of body weight in the previous 5 months, a systolic blood pressure < 110 mm Hg following 1 minute of standing, or residing in a nursing home were excluded.
Intervention. Participants were randomized to SBP targets of ≤ 120 mm Hg (intensive treatment group) or SBP targets of < 140 mm Hg (standard treatment group). After randomization, the baseline antihypertensive regimens were adjusted according to treatment algorithms used in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial [2]. All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. Investigators could also prescribe other antihypertensive medications, which were not provided by the study. The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes. Participants were seen monthly for the first 3 months and then every 3 months thereafter for measurement of their blood pressure to adjust medications to target SBP. The length of follow-up period was planned to be an average of 5 years.
Main outcome measures. The primary study outcome was a composite of non-fatal myocardial infarction, acute coronary syndrome, non-fatal stroke, non-fatal acute decompensated heart failure, and death from cardiovascular causes. Secondary outcomes included all-cause mortality and the composite of primary study outcomes and all-cause mortality. Study outcomes were adjudicated by investigators unaware of study group assignments. Because it is not clear from previous literature if the treatment effect may be modified by the frailty status of the study participants, the study included in its baseline measurements for participants frailty status and an exploratory analysis to examine if the treatment effect varied by frailty status.
Main results. Average age of participants was 80 years, 62% were men, and the baseline systolic blood pressure was 142 mm Hg on average. Overall 31% of participants were classified as frail. The mean SBP achieved in the intensive treatment group was 123 mm Hg during follow-up, and the mean SBP in the standard treatment group was 135 mm Hg. Participants in the intensive treatment group received on average 1 more medication to reach lower SBP. Participants in the intensive group had a lower incidence of the primary outcome, 2.59% per year compared to 3.85% per year in the standard treatment group with a hazard ratio of 0.66 (95% CI, 0.51–0.85). At 3.14 years, the number needed to treat (NNT) for the primary outcome was 27. For all-cause mortality, the intensive treatment group also had lower rates: 73 deaths compared to 107 deaths in the standard treatment group (NNT, 41). In the exploratory analysis, frailty status did not significantly modify the effect of intensive treatment (P = 0.84 for interaction). The rate of adverse events in the intensive treatment group was not statistically significantly different from the standard treatment group; the rate of orthostatic hypotension was also not different between the groups.
Conclusion. Treatment of hypertension to an SBP target of ≤ 120 mm Hg compared with an SBP target of < 140 mm Hg led to lower rates of cardiovascular events and mortality among ambulatory older adults aged 75 and older.
Commentary
Published in 2012, the largest randomized controlled trial on the treatment of hypertension in older adults—the Hypertension in the Very Elderly Trial (HYVET)—found that treatment of older adults aged 80 and older with an SBP of 160 mm Hg with a target of < 150 mm Hg led to a reduction in cardiovascular deaths, strokes, and death from any cause [3]. The current SPRINT study went a step further by lowering the target SBP to 120 mm Hg and found that when compared to a target of < 140 mm Hg, the more intensive control also yielded significant benefits in reducing rates of cardiovascular events and mortality among older adults. Although average SBP reached in the intensive group was higher than the targeted goal of 120 mm Hg (an average of 123 mm Hg during follow-up), it demonstrated the clinical benefits of reducing SBP by over 10 mm Hg when compared with standard treatment group by adding on average 1 antihypertensive medication. The study did not directly tackle the issue of diastolic blood pressure (DBP) levels, though noting that treatment goal should lower DBP to < 90 mm Hg. The intensive treatment group also did not have significantly higher rates of adverse events including orthostatic hypotension and injurious falls, alleviating some of the concerns of clinicians when considering intensifying treatment of hypertension in older adults.
Clinicians often hesitate to intensify hypertension treatment among older adults because previously there has been a lack of evidence that demonstrated conclusively that lowering blood pressure yields clinical benefits [4]. The older adult population is often underrepresented in previous trials of hypertension, and prior observational studies often failed to demonstrate that lower blood pressures associate with better clinical outcomes [5]. Coupled with the concern for the high prevalence of white coat hypertension, orthostatic hypotension, falls, and frailty in the older adult population, clinicians are often concerned that intensifying hypertension treatment may do more harm than good [4]. The current study took great care in tackling some of these issues by including a measurement of frailty, by allowing older adults with postural changes in blood pressure to be included (except for those with standing blood pressure in very low range of < 110 mm Hg), and by tracking adverse events including orthostatic hypotension and injurious falls. The results should help to provide the evidence to convince clinicians that there is substantial value in intensifying hypertension treatment among ambulatory older adults and dispel some of the concerns that clinicians may have regarding its potential harms. Of note, the study excluded older adults that perhaps represent the frailest group of the older adult population—those living in nursing homes, those with dementia, and those with life expectancy of less than 3 years. The study results should not extrapolate to these groups. The analysis examining if treatment effect is consistent among those who are frail should be considered exploratory in nature, as pointed out by the study authors and the editorial to the article [6]. Further studies are needed to examine this issue.
Applications for Clinical Practice
The current study provides strong evidence that intensifying antihypertensive treatment to SBP in the range of 120 mm Hg confers clinical benefits to older ambulatory adults aged 75 and older. The current guidelines published by the Eighth Joint National Committee (JNC 8) recommends that treatment in the general population aged ≥ 60 years should consist of initiating pharmacologic treatment at SBP ≥ 150 mm Hg and treat to a goal SBP < 150 mm Hg [7]. Given the findings from the current study, the guidelines should be revised to reflect the new evidence generated from the current study. Although cardiovascular events and mortality are important clinical outcomes, other outcomes important to the older adult population should also be examined such as quality of life and functional outcomes. The SPRINT study did include these outcomes in its protocol and we look forward to additional insights regarding treatment impact on these important outcomes.
—William W. Hung, MD, MPH
Study Overview
Objective. To determine the effects of intensive (≤ 120 mm Hg) compared with standard (< 140 mm Hg) systolic blood pressure (SBP) targets in adults aged 75 years and older with hypertension.
Design. Randomized controlled trial.
Setting and participants. Participants were a pre-specified subgroup of adults aged 75 years and older from the Systolic Blood Pressure Intervention Trial (SPRINT), an open-label trial conducted at 102 clinical sites in the United States [1]. Participants were included if they had a systolic blood pressure of 130–180 mm Hg and were at increased risk for cardiovascular disease, based on a history of clinical or subclinical cardiovascular disease, chronic kidney disease, or a 10-year Framingham general cardiovascular disease risk score ≥ 15%. Adults with type 2 diabetes, a history of stroke, symptomatic heart failure within the previous 6 months or reduced left ventricular ejection fraction of less than 35%, a clinical diagnosis of dementia, an expected survival of less than 3 years, unintentional weight loss greater than 10% of body weight in the previous 5 months, a systolic blood pressure < 110 mm Hg following 1 minute of standing, or residing in a nursing home were excluded.
Intervention. Participants were randomized to SBP targets of ≤ 120 mm Hg (intensive treatment group) or SBP targets of < 140 mm Hg (standard treatment group). After randomization, the baseline antihypertensive regimens were adjusted according to treatment algorithms used in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial [2]. All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. Investigators could also prescribe other antihypertensive medications, which were not provided by the study. The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes. Participants were seen monthly for the first 3 months and then every 3 months thereafter for measurement of their blood pressure to adjust medications to target SBP. The length of follow-up period was planned to be an average of 5 years.
Main outcome measures. The primary study outcome was a composite of non-fatal myocardial infarction, acute coronary syndrome, non-fatal stroke, non-fatal acute decompensated heart failure, and death from cardiovascular causes. Secondary outcomes included all-cause mortality and the composite of primary study outcomes and all-cause mortality. Study outcomes were adjudicated by investigators unaware of study group assignments. Because it is not clear from previous literature if the treatment effect may be modified by the frailty status of the study participants, the study included in its baseline measurements for participants frailty status and an exploratory analysis to examine if the treatment effect varied by frailty status.
Main results. Average age of participants was 80 years, 62% were men, and the baseline systolic blood pressure was 142 mm Hg on average. Overall 31% of participants were classified as frail. The mean SBP achieved in the intensive treatment group was 123 mm Hg during follow-up, and the mean SBP in the standard treatment group was 135 mm Hg. Participants in the intensive treatment group received on average 1 more medication to reach lower SBP. Participants in the intensive group had a lower incidence of the primary outcome, 2.59% per year compared to 3.85% per year in the standard treatment group with a hazard ratio of 0.66 (95% CI, 0.51–0.85). At 3.14 years, the number needed to treat (NNT) for the primary outcome was 27. For all-cause mortality, the intensive treatment group also had lower rates: 73 deaths compared to 107 deaths in the standard treatment group (NNT, 41). In the exploratory analysis, frailty status did not significantly modify the effect of intensive treatment (P = 0.84 for interaction). The rate of adverse events in the intensive treatment group was not statistically significantly different from the standard treatment group; the rate of orthostatic hypotension was also not different between the groups.
Conclusion. Treatment of hypertension to an SBP target of ≤ 120 mm Hg compared with an SBP target of < 140 mm Hg led to lower rates of cardiovascular events and mortality among ambulatory older adults aged 75 and older.
Commentary
Published in 2012, the largest randomized controlled trial on the treatment of hypertension in older adults—the Hypertension in the Very Elderly Trial (HYVET)—found that treatment of older adults aged 80 and older with an SBP of 160 mm Hg with a target of < 150 mm Hg led to a reduction in cardiovascular deaths, strokes, and death from any cause [3]. The current SPRINT study went a step further by lowering the target SBP to 120 mm Hg and found that when compared to a target of < 140 mm Hg, the more intensive control also yielded significant benefits in reducing rates of cardiovascular events and mortality among older adults. Although average SBP reached in the intensive group was higher than the targeted goal of 120 mm Hg (an average of 123 mm Hg during follow-up), it demonstrated the clinical benefits of reducing SBP by over 10 mm Hg when compared with standard treatment group by adding on average 1 antihypertensive medication. The study did not directly tackle the issue of diastolic blood pressure (DBP) levels, though noting that treatment goal should lower DBP to < 90 mm Hg. The intensive treatment group also did not have significantly higher rates of adverse events including orthostatic hypotension and injurious falls, alleviating some of the concerns of clinicians when considering intensifying treatment of hypertension in older adults.
Clinicians often hesitate to intensify hypertension treatment among older adults because previously there has been a lack of evidence that demonstrated conclusively that lowering blood pressure yields clinical benefits [4]. The older adult population is often underrepresented in previous trials of hypertension, and prior observational studies often failed to demonstrate that lower blood pressures associate with better clinical outcomes [5]. Coupled with the concern for the high prevalence of white coat hypertension, orthostatic hypotension, falls, and frailty in the older adult population, clinicians are often concerned that intensifying hypertension treatment may do more harm than good [4]. The current study took great care in tackling some of these issues by including a measurement of frailty, by allowing older adults with postural changes in blood pressure to be included (except for those with standing blood pressure in very low range of < 110 mm Hg), and by tracking adverse events including orthostatic hypotension and injurious falls. The results should help to provide the evidence to convince clinicians that there is substantial value in intensifying hypertension treatment among ambulatory older adults and dispel some of the concerns that clinicians may have regarding its potential harms. Of note, the study excluded older adults that perhaps represent the frailest group of the older adult population—those living in nursing homes, those with dementia, and those with life expectancy of less than 3 years. The study results should not extrapolate to these groups. The analysis examining if treatment effect is consistent among those who are frail should be considered exploratory in nature, as pointed out by the study authors and the editorial to the article [6]. Further studies are needed to examine this issue.
Applications for Clinical Practice
The current study provides strong evidence that intensifying antihypertensive treatment to SBP in the range of 120 mm Hg confers clinical benefits to older ambulatory adults aged 75 and older. The current guidelines published by the Eighth Joint National Committee (JNC 8) recommends that treatment in the general population aged ≥ 60 years should consist of initiating pharmacologic treatment at SBP ≥ 150 mm Hg and treat to a goal SBP < 150 mm Hg [7]. Given the findings from the current study, the guidelines should be revised to reflect the new evidence generated from the current study. Although cardiovascular events and mortality are important clinical outcomes, other outcomes important to the older adult population should also be examined such as quality of life and functional outcomes. The SPRINT study did include these outcomes in its protocol and we look forward to additional insights regarding treatment impact on these important outcomes.
—William W. Hung, MD, MPH
1. Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive vs standard blood pressure control. N Engl J Med 2015;373:2103–16.
2. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85.
3. Beckett N, Peters R, Tuomilehto J et al. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial. BMJ 2011;344:d7541.
4. Morley JE. Systolic hypertension should not be treated in persons aged 80 and older until blood pressure is greater than 160 mmHg. J Am Geriatr Soc 2013;61:1197–8.
5. Jacobs JM, Stessman J, Ein-Mor E, et al. Hypertension and 5-year mortality among 85-year-olds: The Jerusalem Longitudinal Study. J Am Med Dir Assoc 2012;13:759.e1–759.e6.
6. Chobanian AV. SPRINT results in older patients: How low to go? JAMA 2016;315:2669–70.
7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20.
1. Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive vs standard blood pressure control. N Engl J Med 2015;373:2103–16.
2. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85.
3. Beckett N, Peters R, Tuomilehto J et al. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial. BMJ 2011;344:d7541.
4. Morley JE. Systolic hypertension should not be treated in persons aged 80 and older until blood pressure is greater than 160 mmHg. J Am Geriatr Soc 2013;61:1197–8.
5. Jacobs JM, Stessman J, Ein-Mor E, et al. Hypertension and 5-year mortality among 85-year-olds: The Jerusalem Longitudinal Study. J Am Med Dir Assoc 2012;13:759.e1–759.e6.
6. Chobanian AV. SPRINT results in older patients: How low to go? JAMA 2016;315:2669–70.
7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20.