Hypertension in Older Adults in the Wake of the Systolic Blood Pressure Intervention Trial

Hypertension is the most common chronic condition that geriatricians and other physicians caring for older adults treat in clinical practice. Management of hypertension in this population is a conundrum for healthcare professionals, older adults, and their families. Several studies have shown a decrease in cardiovascular morbidity associated with treatment of hypertension in older adults.1, 2 Nonpharmacological interventions for hypertension, such as a low-sodium diet that may make food less pleasurable in people with diminished taste sensation, and exercise, which may be limited because of musculoskeletal conditions, are often challenging for older adults. Pharmacological treatment is fraught with hazards in older adults, especially those with multiple morbidities. As practicing geriatricians have witnessed all too often, drugs with hypotensive effects are among the most common agents associated with adverse events resulting in hospitalization.3 Hypotension and related falls are also among the most common adverse events that occur in skilled nursing facilities.4 As with most clinical trials of pharmacological treatment for any condition in older adults, studies that have shown benefit from antihypertensive therapy have for the most part systematically excluded the types of people that geriatricians commonly see in practice,5 making evidence-based treatment decisions challenging. The Systolic Blood Pressure Intervention Trial (SPRINT) offers new data that can assist clinicians in treatment decisions for this common condition. SPRINT randomized 9,361 individuals aged 50 and older (28.2% ≥75) with systolic blood pressure of 130 to 180 mmHg to a blood pressure treatment target of less than 120 mmHg or to a target of less than 140 mmHg.6 The trial was terminated early after a median follow-up of 3.26 years because there was a 25% reduction in the primary composite outcome of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death in the intensive treatment arm (1.65%/year event rate vs 2.19%/year; hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.64–0.89, p<.001). All-cause mortality was 27% lower (HR=0.73, 95% CI=0.60–0.90, p=.003). In individuals aged 75 and older (N=2,686, mean aged 79.9, 37.9% women), the effect of intensive treatment on the primary outcome was at least as great as in younger adults (HR=0.66, 95% CI=0.51–0.85 vs HR=0.80, 95% CI=0.64–1.00, p-value for interaction=.32); all-cause mortality was lower as well (HR=0.67, 95% CI=0.49–0.91).7 Moreover, results were similar across predefined fitness levels (fit, less fit, frail) and in individuals with slow gait speed (<0.8 m/s). The beneficial effects of intensive blood pressure reduction in SPRINT occurred at a cost of higher rates of the serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure (but not injurious falls), with similar findings in individuals younger than 75 and 75 and older.6, 7 In this issue of the Journal of the American Geriatrics Society, Sink and colleagues provide a more detailed analysis of 3 serious adverse events of particular concern to geriatricians and to all clinicians treating hypertension in older adults—syncope, hypotension, and falls.8 For this analysis, serious adverse events were defined as those that were "fatal or life-threatening, resulted in significant or permanent disability, required hospitalization, or that the investigators judged represented significant hazards or harm to the participant."8 The main findings were that, after extensive adjustment for numerous potential confounding variables, randomization to the intensive treatment arm was associated with significantly greater risk of hypotension (HR=1.67, 95% CI=1.21–2.32, p=.002) and possibly syncope (HR=1.32, 95% CI=0.98–1.75, p=.07) but not falls (HR=0.98, 95% CI=0.75–1.29) or injurious falls. Older age, frailty, and chronic kidney disease were also associated with greater risk of all three adverse events, but there was no interaction between age and treatment assignment with respect to any of the adverse events. In other words, the effect of intensive treatment on serious adverse events was similar in younger and older adults, including those aged 85 and older.8 SPRINT was a landmark trial, in part because it was the first major study to enroll individuals with systolic blood pressure in the range of 130 to 160 mmHg and to demonstrate that more intensive blood pressure reduction reduces major cardiovascular events and mortality, including in individuals aged 75 and older. Nonetheless, SPRINT has generated controversy and raised questions about the applicability of the study findings to older adults commonly encountered in routine clinical practice. SPRINT excluded individuals with diabetes mellitus, prior stroke, advanced kidney disease, a recent cardiovascular event, dementia, nursing home residence, life expectancy less than 3 years, and several other conditions (Table 1).6, 7 Based on an analysis of data from the 2007 to 2012 National Health and Nutrition Examination Surveys (NHANES), only 34.6% of U.S. adults aged 75 and older fulfill SPRINT eligibility criteria. Of adults in this age group with treated hypertension, only 31.3% would be eligible for SPRINT.9 Thus, approximately two-thirds of adults aged 75 and older would have been excluded from SPRINT, and the generalizability of the SPRINT findings to this population is at best uncertain. Furthermore, because the prevalence of several SPRINT exclusion criteria, notably dementia, nursing home residence, and life expectancy less than 3 years, all increase inexorably with age, the proportion of adults to whom the SPRINT results may apply declines progressively with age. Another controversy about the SPRINT trial relates to the methodology of blood pressure ascertainment. Blood pressure in SPRINT "was determined using the mean of three properly-sized automated cuff readings, taken 1 minute apart after 5 minutes of quiet rest without staff in the room."7 The SPRINT method, although providing valid and reproducible measurements in the context of a clinical trial, may underestimate "typical" office blood pressure measured using a standard sphygmomanometer in a busy office setting by up to 15 mmHg,10 although not all studies have shown such a discrepancy.11 Thus, there is concern that the intensive treatment target of less than 120 mmHg tested in SPRINT may correspond to a somewhat higher usual office blood pressure. Concern about potential differences between SPRINT blood pressures and usual office blood pressures also invokes the question of "how low is too low." Although intensive treatment was not associated with greater risk of injurious falls in SPRINT, a propensity analysis of 4,961 Medicare beneficiaries found that antihypertensive medications were associated with greater risk of serious fall-related injuries, especially in those with prior fall injuries.12 Initiation of antihypertensive therapy has also been associated with greater risk of hip fractures during the ensuing 45 days.13 Because almost all individuals aged 75 and older enrolled in SPRINT were already taking 1 or more antihypertensive medications at baseline (mean 1.9 ± 1.0 drugs), SPRINT would not have captured fall risk associated with initiation of antihypertensive therapy. In a small study examining the association between on-treatment blood pressure and cognitive decline in older adults with mild cognitive impairment or overt dementia, those with mean daytime systolic blood pressure of 128 mmHg or lower had greater decline in cognitive function over a median follow-up of 9 months than those with higher daytime blood pressure.14 Conversely, a randomized clinical trial of discontinuing antihypertensive treatment in individuals aged 75 and older with mild cognitive deficits (Mini-Mental State Examination scores of 21–27) demonstrated no improvement in cognitive, psychological, or daily function.15 Self-reported outcomes in SPRINT, as assessed using the physical and mental component scores of the RAND 12-item health survey and the Patient Health Questionnaire 9-item depression scale, did not differ between individuals randomized to the intensive and conventional treatment targets.16 The results of the more comprehensive SPRINT Memory and cognition IN Decreased hypertension (MIND) study, which will provide a detailed assessment of the association between blood pressure control and cognition, have not been reported.17 Although individuals with dementia were excluded, the median Montreal Cognitive Assessment score was 22.0 (interquartile range 19–25) in participants aged 75 and older enrolled in SPRINT reflecting mild cognitive impairment.7 Hence, the SPRINT-MIND study should provide valuable insights into the effects of antihypertensive therapy on cognition in older adults with mild cognitive impairment. So, how should clinicians manage geriatric hypertension in the post-SPRINT era? The recently released 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, which the American Heart Association and American College of Cardiology have developed in collaboration with the American Geriatrics Society and several other professional societies, provides two recommendations for treatment of hypertension in older adults (Table 2).18 These recommendations strike a nice balance between implementation of evidence-based medicine for older adults to whom the evidence applies (approximately one-third of persons ≥75) while providing considerable flexibility in clinical decision-making for the remaining two-thirds of persons in this age group to whom the applicability of the current evidence base is less certain. Additional caveats are that blood pressure targets should be modified if they cannot be safely achieved without undue side effects (including significant orthostatic hypotension) and that excessive blood pressure reduction (e.g., <120 mmHg) should be avoided, particularly in older adults at risk of falls or cognitive dysfunction. Moreover, older adults' blood pressure may decrease over time and require less antihypertensive therapy, which may herald a trajectory toward death.19, 20 In these individuals, careful "deprescribing" of antihypertensive medications, as well as other medications with potential hypotensive effects, should be considered.21, 22 SPRINT has helped our field further define the management of hypertension in older adults, but older adults are heterogeneous, and evidence-based management must be combined with a strong dose of person-centered care.23 Person-centered care helps clinicians account for many factors that affect treatment decisions in addition to evidence from randomized trials, such as the individual's prognosis, goals of care, tolerance for risk of adverse side effects, and costs of treatment, among other considerations. Although SPRINT represents an extraordinary achievement that has already prompted a paradigm shift in the diagnosis and treatment of hypertension in younger and older adults, additional research is needed in the wake of SPRINT to further delineate optimal approaches to the prevention and treatment of high blood pressure in the expanding geriatric population. Conflict of interest: None. Author Contributions: Dr. Rich drafted the manuscript, and Dr. Ouslander contributed substantive revisions. Both authors approved the final version. Sponsor's Role: N/A.

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