Managing Hypertension in Older Adults

Recent Guidelines Explained

RELEASE DATE:

February 28, 2018

EXPIRATION DATE:

February 29, 2020

FACULTY:

Donna M. Lisi, PharmD, BCPS, BCPP, BCGP
Adjunct Faculty, Union County College
Division of Allied Health
Plainfield, New Jersey
Consultant Clinical Pharmacist/Medical Writer/Educator
Somerset, New Jersey

FACULTY DISCLOSURE STATEMENTS:

Dr. Lisi has no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

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Pharmacy
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Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate the pharmacist about the similarities and differences between recent clinical practice guidelines and about patient-related and medication-related factors affecting the management of hypertension (HTN) in older adults.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Identify discrepancies in the various clinical practice guidelines concerning initiation of antihypertensive therapy and target blood pressure goals in older adults.
  2. Recognize the role of patient-related factors, including comorbidities, in the management of HTN in older adults.
  3. Discuss medication-related factors and their impact on managing HTN in older adults.
  4. Develop a treatment plan for HTN management in older adults that incorporates medication therapy management principles.

ABSTRACT: Hypertension is extremely common in older adults, and its prevalence increases with age. If it is left untreated or is inadequately treated, hypertension contributes to the risk of stroke, myocardial infarction, heart failure, and renal failure. In 2017, two major guidelines were published that provided recommendations for managing hypertension in older adults, but there are discrepancies between them. Both patient-specific factors and medication-related factors can affect the outcome of antihypertensive regimens. Pharmacists must be familiar with evidence-based guidelines on the management of hypertension in older adults in order to optimize their patients' antihypertensive regimens.

Hypertension (HTN) is defined as two or more elevated blood pressure (BP) readings obtained on two or more occasions. Stage 1 HTN is considered a systolic BP reading (SBP) of 130 to 139 mmHg or a diastolic BP (DBP) reading of 80 to 89 mmHg. Stage 2 HTN is an SBP ≥140 mmHg or a DBP ≥90 mmHg.1 Left untreated or inadequately treated, HTN contributes to the risk of stroke, myocardial infarction, heart failure, and renal failure.

Hypertension is extremely common in older adults. An analysis of National Center for Health Statistics data from 2011 to 2014 on the prevalence and control of HTN in U.S. adults found that HTN was present in 29% of the general adult population. The prevalence increased with age as follows: 18 to 39 years, 7.3%; 40 to 59 years, 32.2%; and ≥60 years, 64.9%. HTN was adequately controlled in 53% of the total population, which is consistent with the rate in persons aged ≥60 years (52.5%).2

PHYSIOLOGICAL CHANGES THAT PREDISPOSE OLDER ADULTS TO HTN

A number of age-related physiological changes predispose older adults to HTN development. As collagen increases and elastin decreases, the walls of large arteries, including the aorta, thicken and lose elasticity, as evidenced by an increase in pulse wave velocity (a measure of arterial stiffness). This increase is associated with a rise in SBP. Accompanying the rise in SBP is a decline (or no change) in DBP, which results in isolated systolic HTN (ISH). The decrease in DBP reduces coronary perfusion during diastole and may lead to myocardial ischemia.3-5

Metabolic syndrome, oxidative stress, and inflammation secondary to immunosenescence contribute to age-related arterial stiffening and HTN. Neurohormonal dysfunction leads to diminished sympathetic baroreflex sensitivity, which in turn results in sympathetic activation and BP elevation. Salt sensitivity plays a role in vascular stiffening and development of HTN, and dysregulation of aldosterone affects vascular remodeling. Chronic elevated SBP leads to left ventricular hypertrophy, which increases myocardial oxygen demand.3-5

CLINICAL TRIALS ON HTN MANAGEMENT IN OLDER ADULTS

TABLE 1 identifies landmark clinical trials that have examined the management of HTN in older adults.6-20 These studies are inconsistent in their definition of "older adult," target BP goals, goals for initiating therapy, endpoints, and clinical interventions, making comparisons difficult. A detailed discussion of these trials is beyond the scope of this article.


tbl1

Noteworthy among these studies, the recent Systolic Blood Pressure Intervention Trial (SPRINT) has reignited the debate about the lower limit of the target SBP goal for older adults.20 SPRINT randomized 9,361 patients with an SBP ≥130 mmHg who were at increased cardiovascular (CV) risk to a target BP goal of either SBP <120 mmHg (intensive group) or SBP <140 mmHg (standard group). Nursing home residents and patients with diabetes, history of stroke, symptomatic heart failure within the past 6 months or ejection fraction <35%, dementia, expected survival <3 years, unintentional loss of >10% of body weight in the past 6 months, or SBP <110 mmHg after 1 minute of standing were excluded, which limited the generalizability of the findings. The average age of both treatment groups was 67.9 years, and 80% of patients were aged ≥75 years.

In a SPRINT subgroup analysis of patients aged ≥75 years, both fatal and nonfatal CV events (hazard ratio [HR] 0.66; CI, 0.51-0.85) and all-cause mortality (HR 0.67; CI, 0.49-0.91) were significantly reduced in the intensive group compared with the standard group. The rate of serious adverse events (e.g., hypotension, syncope, electrolyte abnormalities, acute kidney injury, injurious falls) did not differ between the groups.21

CLINICAL GUIDELINES ON HTN MANAGEMENT IN OLDER ADULTS

There are discrepancies in clinical practice recommendations concerning initiation of treatment for HTN and target BP goals for older adults. In 2017, two major guidelines were published that included recommendations on HTN management in older adults.1,22 TABLE 2 summarizes the pre-2017 guidelines on HTN management in older adults that still influence patient care.23-26


tbl2

As is evidenced in these guidelines, recommendations vary as to when to initiate treatment and what the target BP goal should be for older adults. This has added to the complexity of HTN management in older patients. Ideal target SBP goals and when to initiate treatment remain elusive.

ACP/AAFP Clinical Practice Guideline
In 2017, the American College of Physicians and the American Academy of Family Physicians (ACP/ AAFP) released a clinical guideline on pharmacologic treatment of HTN in adults aged ≥60 years. In the guideline, ACP/AAFP weighed benefits versus harms associated with higher versus lower SBP targets. Outcomes assessed included all-cause mortality, morbidity and mortality related to stroke, major cardiac events (i.e., fatal and nonfatal myocardial infarction and sudden cardiac death), and harms.22

In the development of this guideline, major clinical trials that examined the intensity of lowering BP in older adults were reviewed. Most benefit associated with HTN management in this population was seen in patients with moderate-to-severe HTN (i.e., SBP >160 mmHg) in whom a BP reduction to SBP >140 mmHg was achieved. High-quality evidence demonstrated decreases in all-cause mortality, stroke, and cardiac events when initial SBP readings of ≥160 mmHg were reduced to a target SBP reading of <150 mmHg. When lower SBP targets (<140 mmHg) were used, low-quality evidence showed no significant reduction in all-cause mortality or cardiac events, but moderate-quality evidence has shown a reduction in stroke risk. Some of the methodological shortcomings affecting outcome were that the study population often did not achieve target BP goals and that differences between the intensive-treatment and control groups were minimal.22

Subgroup analysis involving high-quality evidence demonstrated a similar risk reduction for mortality (relative risk [RR] 0.91 [CI, 0.84-0.99] in ≥140 mmHg vs. RR 0.84 [CI, 0.74-0.95] <140 mmHg) and cardiac events (RR 0.78 [CI, 0.68-0.93] in ≥140 mmHg vs. RR 0.83 [CI, 0.70-0.94] <140 mmHg) in patients who achieved higher versus lower SBP target goals. This benefit was slightly greater for stroke reduction (RR 0.72 [CI, 0.62-0.82]) in patients achieving a target SBP ≥140 mmHg than in those achieving a target SBP <140 mmHg (RR 0.81 [CI0.66-0.96]). Again, methodological issues such as statistical heterogeneity may affect the generalizability of these data.22

In patients with a history of stroke or transient ischemic attack (TIA), moderate-quality evidence showed that treating to an SBP of 130 to 140 mmHg reduced stroke recurrence (RR 0.76 [CI, 0.66-0.92]), but not cardiac effects (RR 0.78 [CI, 0.61-1.08]) or all-cause mortality (RR 0.98 [CI, 0.85-1.19]). However, no clinical trials assessed the impact of comorbidities on achieving lower versus higher SBP target goals because patients with heart failure, recent CV events, abnormal renal function, cancer or other life-limiting illnesses, dementia or diminished function, and diabetes were often excluded from these studies. Studies using DBP as a treatment goal are insufficient.22

It was also observed that treating to an SBP of ≤140 mmHg increased treatment withdrawals due to adverse events, specifically cough and hypotension. The risk of syncope was increased, but there was no difference in renal outcomes, functional status, or fall risk. However, these findings were based on low-quality evidence. Moderate-quality evidence found no effect of SBP treatment goals on degree of cognitive decline or dementia, fractures, or quality of life.22 In the Secondary Prevention of Small Subcortical Strokes trial, a reduced rate of stroke was observed in patients with previous lacunar strokes with target SBP <130 mmHg compared with those with target SBP 130 to 149 mmHg, but this difference was not significant.18 Age did not appear to be a factor in the development of adverse events; this finding was based on low-quality evidence, however. It should be noted that a subgroup analysis of SPRINT participants that found a decline in all-cause mortality and nonsignificantly lower CV morbidity and mortality and stroke risk at lower BP targets (<120 mmHg) versus higher BP targets (<140 mmHg) was not included in this evaluation.21,22

The three ACP/AAFP recommendations regarding intensity of BP-lowering in older adults were based on reviews sponsored by the U.S. Department of Veterans Affairs. Target BP goals were classified as higher (SBP <150 mmHg) or lower (SBP ≤140 mmHg).22 The recommendations in the ACP/AAFP clinical practice guideline are as follows22:

  1. To reduce the risk of mortality, stroke, or cardiac events, initiate treatment when SBP is persistently ≥150 mmHg, in order to achieve a target SBP goal of <150 mmHg. This is graded as a strong recommendation supported by high-quality evidence.
  2. In patients with a history of stroke or TIA, initiate or intensify pharmacologic treatment to achieve a target SBP <140 mmHg to reduce the risk of recurrent stroke. This is graded as a weak recommendation based on moderate-quality evidence.
  3. Based on individualized assessment of high CV risk, pharmacologic treatment should be initiated or intensified to achieve a target SBP <140 mmHg in order to reduce the risk of stroke or cardiac events. This is graded as a weak recommendation based on low-quality evidence. CV risk is increased in patients with known vascular disease, diabetes, chronic kidney disease (CKD) (glomerular filtration rate <45 mL/min/1.73 m2), or metabolic syndrome and in older patients.22 Implementation of these recommendations should be accompanied by a discussion of benefit versus harm with the patient. Appropriate nonpharmacologic interventions, such as weight loss, dietary modifications (e.g., reducing sodium and fat intake), and increased physical activity, should be recommended.22

An accompanying systematic review and metaanalysis to the ACP/AAFP guideline concluded that treatment of SBP to at least <150/90 significantly improves health outcomes in older adults. However, it warned that evidence was less consistent supporting a target SBP <120 mmHg in most older persons, except those at high risk (this was based on the findings of one study). Although lower SBP targets were not associated with falls or cognitive decline, they were linked to hypotension, syncope, and greater medication burden.27

ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline
This update, which was published in November 2017 by the National Heart, Lung, and Blood Institute (NHLBI) and supersedes the 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), provides guidance on the assessment and management of HTN in older adults, as well as in those with comorbidities.1 It also incorporates information from studies on office-based BP-related risk of CV disease, ambulatory and home BP monitoring, and telemedicine, all areas of relevance to the older population. This guideline is the most comprehensive update to JNC7. JNC8, which was published in 2014, was meant only to address three treatment-related questions in an evidence-based guideline and was not released by the NHLBI.23,28

Unlike JNC8, which was criticized because of its recommendations to increase the target SBP from 140 to 150 mmHg in persons aged ≥60 years without diabetes mellitus or CKD and not to initiate treatment until SBP ≥150 mmHg is achieved, the new guideline takes a less controversial position.29

Two recommendations regarding the treatment of HTN in older persons are offered29:

  1. Treatment of HTN with an SBP treatment goal of <130 mmHg is recommended for noninstitutional, ambulatory, community-dwelling adults aged ≥65 years with an average SBP ≥130 mmHg.
  2. For patients aged ≥65 years with HTN and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/benefit are reasonable for decisions regarding intensity of BP-lowering and choice of antihypertensive drugs.

The guideline also advises performance of an atherosclerotic CV disease (ASCVD) risk assessment in all older adults. It is recommended that American College of Cardiology/AHA Pooled Cohort Equations (http://tools.acc.org/ASCVD-Risk-Estimator/) be used to estimate 10-year risk of ASCVD to establish a BP threshold for treatment. However, this equation has been validated only for patients aged 45 to 79 years who are not on concurrent statin therapy. For those aged ≥79 years, the 10-year ASCVD risk is considered to be >100%. In general, 88% of adults aged ≥65 years have a 10-year predicted ASCVD risk >10% or a history of CVD. This risk score would place older adults in the high-risk category that requires initiation of antihypertensive drug therapy at BP ≥130/80 mmHg.1,30,31

The guideline authors acknowledged that the treatment of HTN in older adults can be challenging because of heterogeneity in comorbidities, polypharmacy, frailty, cognitive impairment, and variable life expectancy.1

PATIENT-RELATED FACTORS IN HTN MANAGEMENT IN OLDER ADULTS

Guidelines are especially necessary for older adults because this population is most likely to have multiple disease processes occurring simultaneously. Although clinical trials and practice guidelines can provide recommendations for HTN management in older adults, patient-specific factors also must be addressed. The presence of comorbidities increases the complexity of managing hypertensive patients. Until recently, guidance on how to manage hypertensive patients with multiple comorbidities was limited.32

In older populations, comorbidities and other factors are numerous and can affect the benefits and harms of a pharmacotherapy regimen. Comorbidities addressed in the new HTN guidelines include stable ischemic heart disease, heart failure, CKD, cerebrovascular disease, peripheral arterial disease, diabetes, metabolic syndrome, atrial fibrillation and valvular heart disease, and aortic disease. Other patient-specific factors pertinent to older adults that are also covered in the new guidelines include frailty, cognitive impairment, sexual dysfunction, orthostasis/syncope, race, resistant hypertension, preoperative considerations, and interoffice BP variability (e.g., white-coat HTN, masked HTN).1,33 However, the new guidelines do not address HTN management in patients with chronic obstructive pulmonary disease, arthritis, hepatitis, depression, or osteoporosis, which are common comorbidities in older adults.34

A more detailed discussion of these factors is beyond the scope of this article.

MEDICATION-RELATED FACTORS IN MANAGING HTN IN OLDER ADULTS

Medication-related issues can enhance the complexity of a drug regimen. A medication therapy management–based comprehensive medication review can help identify these potential medication-related problems.35 The following sections discuss some medication-related factors that affect BP control in older adults.

Polypharmacy: Older adults frequently require more than one antihypertensive agent to lower BP. According to the 2011 AACF/AHA guideline, an average of two to four antihypertensives are required for BP control in most high-risk hypertensive patients with comorbid conditions, such as CKD or diabetes mellitus.26 In the older hypertensive patient, polypharmacy is associated with an increased risk of adverse events (falls, hyper- or hypokalemia, heart failure, BP exacerbations).36 Caution is advised in the management of frail, very old patients with antihypertensives.37

Drug-Drug Interactions: The rate of potential drug-drug interactions in medications used by hypertensive patients was found to be 71.5%. Of these drug interactions, 55.2% were due to pharmacodynamics interactions, 4.8% were related to pharmacokinetic interactions, and 32.2% involved alterations in serum potassium levels. The most common drug-drug interaction involved atenolol and amlodipine, which can have additive or synergistic negative effects on heart rate and on cardiac conduction and contractility.38

Drug-Disease Interactions: Several recent reviews have been published on drug-induced HTN. The pharmacist should be aware of agents that can induce HTN. It is important to take a complete medicinal product history while counseling the patient with HTN. This should include OTC products, herbal products, dietary supplements, and other alternative and complementary medicines, in addition to prescription medications. There are several mechanisms by which medications can exacerbate HTN (TABLE 3).39-41


tbl3

Potentially Inappropriate Drug Regimens: Potentially inappropriate antihypertensive use affects more than one-half of elderly patients. Twenty-eight percent of older adults are overprescribed antihypertensives, whereas 35% are underprescribed BP-lowering medications even when they are appropriate.42 A study of patients aged ≥65 years found that failure to use antihypertensives was one of the most common potential prescribing omissions. Conversely, overprescribing of antihypertensives and diuretics with resultant bradycardia, hypotension, and dehydration was the second most common reason for medication-related readmission in persons aged ≥65 years.43 The Beers Criteria and the STOPP (Screening Tool of Older People's Prescriptions) criteria have identified potentially inappropriate medication additions, whereas the START (Screening Tool to Alert to Right Treatment) criteria have identified potentially inappropriate omissions from the antihypertensive drug regimen.44,45

Nonadherence: This problem is common, with 31.2% of patients with HTN and comorbidities demonstrating nonadherence to an antihypertensive medication regimen.46 Among Medicare beneficiaries who initiated HTN treatment between 2007 and 2012, approximately one-third were nonadherent. Factors associated with increased risk of nonadherence included racial/ethnic minority status, Medicaid buy-in status (an indicator of low income), and polypharmacy.47 Lack of adherence to an antihypertensive regimen has been associated with increased hospitalization and mortality from acute myocardial infarction, ischemic heart disease, cerebral hemorrhage, and cerebral infarction.48

Adverse Drug Events (ADEs): Older adults may be more susceptible to ADEs associated with antihypertensive medications because of physiological changes, comorbidity, excessive doses, and drug interactions. A recent paper reviewed the tolerability of antihypertensives in older adults.49 Based on data from the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD) and SPRINT studies, male sex, current smoking, statin use, elevated serum creatinine, and increased lipid levels were associated with a greater risk of experiencing serious ADEs.50 In addition to the development of orthostasis (resulting in injurious falls) or electrolyte imbalances, other potential ADEs include increased risk of CV and cerebrovascular disease secondary to the J-curve phenomenon (in which lowering BP beyond a critical point results in harm secondary to impaired organ perfusion); adverse effects on glucose control; and possible risk of certain age-related malignancies.51

CONCLUSION

Recently, two guidelines were issued regarding initiation of antihypertensive treatment and target SBP goals for older adults with HTN. Despite the conflicting recommendations and in light of recent evidence from SPRINT, older patients with an SBP ≥160 mmHg whose SBP is reduced to <150 mmHg show the greatest decreases in morbidity and mortality. Further SBP reductions in patients with a history of stroke or TIA have been shown to prevent recurrent stroke. In stable, noninstitutional, ambulatory, community-dwelling adults aged ≥65 years with an average SBP of ≥130 mmHg, a treatment goal of <130 mmHg has been recommended. Clinicians must be mindful of the J-curve phenomenon when intensive SBP goals are attempted. Older adults should be closely assessed for adverse effects on health or quality of life secondary to antihypertensive therapy. When antihypertensive treatment is being recommended, comorbidities must be taken into account. Lower SBP may not be appropriate for frail, older adults with high comorbidity or limited life expectancy; some experts have advised withholding treatment in patients who are frail or medically compromised.

Treatment regimens should be individualized for all older adults, taking into consideration the factors discussed in this article. As drug experts, pharmacists are ideally suited to interpret evidence-based medicine guidelines and develop individualized, patient-focused recommendations to optimize their patients' antihypertensive regimens.

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