SPRINT Trial: Systolic Blood Pressure in Older Adults >75

Both, February 2014 JNC8 and January 2017 ACP/AAFP guidelines recommend a target systolic blood pressure <150 mmHg for adults older then age 60.

SPRINT trial paints a different picture: older individuals with tight systolic blood pressure control <120 mmHg experienced less cardiovascular events and all-cause mortality compared to those with sBP<140 mmHg.

A group of 2,500 participants with average age 80 and without diabetes were followed for 3 years. Side effects were overall similar between patients with sBP<120 and sBP<140 mmHg.



Randomized Trial

June 2016

Importance:  The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain.

Objective:  To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons >75 years of age with hypertension but without diabetes.

Design, Setting, and Participants:  A multicenter, randomized clinical trial of patients aged >75 who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015.

Interventions:  Participants were randomized to an SBP target <120 mm Hg (intensive treatment group, n = 1317) or an SBP target < 140 mm Hg (standard treatment group, n = 1319).

Main Outcomes and Measures:  The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome.

Results:  Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio, HR 0.66 and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67.

The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99. Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51), 5.5% vs 4.0% for acute kidney injury (HR, 1.41), and 4.9% vs 5.5% for injurious falls (HR, 0.91)

Conclusions and Relevance:  Among ambulatory adults aged 75 years or older, treating to an sBP target <120 mm Hg compared with an sBP target <140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.

More from the publication:

In the United States, 75% of persons older than 75 years have hypertension, for whom cardiovascular disease complications are a leading cause of disability, morbidity, and mortality. Current guidelines provide inconsistent recommendations regarding the optimal systolic blood pressure (SBP) treatment target in geriatric populations. European guideline committees have recommended treatment initiation only >160 mmHg for persons aged >80 years old. A recent US guideline, a report from the panel appointed to the Eighth Joint National Committee (JNC 8), recommended a SBP treatment target of 150 mmHg for adults aged >60 years old. However, a report from a minority of the members argued to retain the previously recommended SBP treatment goal of 140 mm Hg, highlighting the lack of consensus.

Whether treatment targets should consider factors such as frailty or functional status is also unknown. Observational studies have noted differential associations among elevated blood pressure (BP) and cardiovascular disease, stroke, and mortality risk when analyses are stratified according to measures of functional status. A recent secondary analysis of the Systolic Hypertension in the Elderly Program showed that the benefit of antihypertensive therapy was limited to participants without a self-reported physical ability limitation. In contrast, analyses from the Hypertension in the Very Elderly Trial (HYVET) showed a consistent benefit with antihypertensive therapy on outcomes irrespective of frailty status.

The Systolic Blood Pressure Intervention Trial (SPRINT) recently reported that participants assigned to an intensive SBP treatment target <120 mm Hg vs the standard SBP treatment goal < 140 mmHg had a 25% lower relative risk of major cardiovascular events and death, and a 27% lower relative risk of death from any cause.This trial was specifically funded to enhance recruitment of a prespecified subgroup of adults aged 75 years or older, and the study protocol also included measures of functional status and frailty. This article details results for the prespecified subgroup of adults aged 75 years or older with hypertension.

These results extend and detail the main SPRINT study findings in community-dwelling persons aged 75 years or older, demonstrating that a treatment goal for SBP <120 mm Hg reduced incident cardiovascular disease by 33% (from 3.85% to 2.59% per year) and total mortality by 32% (from 2.63% to 1.78% per year). Translating these findings into numbers needed to treat suggests that a strategy of intensive BP control for 3.14 years would be expected to prevent 1 primary outcome event for every 27 persons treated and 1 death from any cause for every 41 persons treated. These estimates are lower than those from the overall results of the trial due to the higher event rate in persons aged 75 years or older. In addition, exploratory analysis suggested that the benefit of intensive BP control was consistent among persons in this age range who were frail or had reduced gait speed.

The overall SAE rate was comparable by treatment group, including among the most frail participants. There were no differences in the number of participants experiencing injurious falls or in the prevalence of orthostatic hypotension measured at study visits. These results complement results from other trials demonstrating improved BP control reduces risk for orthostatic hypotension and has no effect on risk for injurious falls.The numbers of participants aged 75 years or older who dropped out of the study, were lost to follow-up, or decided to discontinue the intervention but continued with outcome assessment were low and did not differ by treatment group.

There are several limitations to these results from SPRINT involving participants aged 75 years or older. Even though the trial was designed to enhance recruitment of a prespecified subgroup of adults aged 75 years or older, randomization in SPRINT was not stratified by categories of age. In addition, the trial did not enroll older adults residing in nursing homes, persons with type 2 diabetes or prevalent stroke (because of concurrent BP lowering trials) and individuals with symptomatic heart failure due to protocol differences required to maintain BP control in this condition. Therefore, the results reported in this study among persons aged 75 years or older do not provide evidence regarding treatment targets in these populations. Individuals with these conditions also represent a subset of older persons at increased risk for falls.

Despite excluding some chronic conditions, 30.9% of participants aged 75 years or older in this trial were categorized as frail at baseline, and the distribution of frailty status parallels that estimated for ambulatory, community living populations of similar age. In addition, the proportion of US adults aged 75 years or older who have hypertension and meet the study entry criteria has been estimated to represent 64% of that population using the 2007-2012 National Health and Nutrition Surveys (approximately 5.8 million individuals). Therefore, participants aged 75 years or older in this trial are representative of a sizeable fraction of adults in this age group with hypertension.

There are several important comparisons to make with HYVET, which randomized 3845 patients aged 80 years or older within Europe and Asia (mean age, 83 years [3 years older than SPRINT]; mean entry SBP, 173 mmHg [31 mm Hg higher than SPRINT]) to either therapy with indapamide, with or without the angiotensin-converting enzyme inhibitor perindopril, or placebo with an SBP treatment goal of less than 150 mm Hg. The 2-year between-group SBP difference was 15 mmHg (the active treatment group achieved a mean SBP of 143 mm Hg, slightly higher than the SPRINT baseline SBP). Similar to SPRINT, HYVET was terminated early (at a median follow-up time of 1.8 years) due to significant reductions in the incidence rate of total mortality. A retrospective analysis of the HYVET population conducted to determine its frailty status identified that (1) the cohort’s frailty status was similar to that of community living populations of similar age and (2) the treatment benefits were similar even in the most frail participants. Taken together, current results from SPRINT also reinforce and extend HYVET’s conclusions that risk reductions in cardiovascular disease events and mortality from high BP treatment are evident regardless of frailty status.

Among all participants aged 75 years or older, the SAEs related to acute kidney injury occurred more frequently in the intensive treatment group (72 participants [5.5%] vs 53 participants [4.0%] in the standard treatment group). The differences in adverse renal outcomes may be related to a reversible intrarenal hemodynamic effect of the reduction in BP and more frequent use of diuretics, ACEi, and ARBs in the intensive treatment group. Although there is no evidence of permanent kidney injury associated with the lower BP goal, the possibility of long-term adverse renal outcomes cannot be excluded and requires longer-term follow-up.

Considering the high prevalence of hypertension among older persons, patients and their physicians may be inclined to underestimate the burden of hypertension or the benefits of lowering BP, resulting in under-treatment. On average, the benefits that resulted from intensive therapy required treatment with 1 additional antihypertensive drug and additional early visits for dose titration and monitoring. Future analyses of SPRINT data may be helpful to better define the burden, costs, and benefits of intensive BP control. However, the present results have substantial implications for the future of intensive BP therapy in older adults because of this condition’s high prevalence, the high absolute risk for cardiovascular disease complications from elevated BP, and the devastating consequences of such events on the independent function of older people.

Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.