Medication adherence in patients with hypertension

INTRODUCTION — Suboptimal adherence with prescribed antihypertensive medication and lifestyle changes contributes to the burden of uncontrolled hypertension [1-4]. This problem persists widely despite the success of various programs in attaining high adherence rates with both non-drug (lifestyle modification) [5] and drug regimens [6].

This topic will review the major issues related to nonadherence with antihypertensive medication therapy. A more complete discussion of treatment nonadherence is discussed separately. (See "Adherence to lipid-altering medications and recommended lifestyle changes", section on 'Factors affecting treatment adherence'.)

EPIDEMIOLOGY OF NONADHERENCE — Nonadherence to antihypertensive medication is common, and varies with age, sex, antihypertensive type, and other factors including health insurance [7,8]. As examples:

●In a United States study including 149 patients with uncontrolled hypertension (monitored with electronic pill boxes), 42 percent were nonadherent with treatment, defined as taking less than 80 percent of prescribed antihypertensive medication [9].

●In another study, adherence to antihypertensive medications was evaluated among 1348 hypertensive patients in the United Kingdom and Czechoslovakia with suspected nonadherence or difficult-to-control hypertension. Adherence was assessed by detection of antihypertensive medications with high-performance liquid chromatography-tandem mass spectrometry of patient urine and serum specimens. Partial and complete nonadherence ranged from 20 to 27 percent and from 12 to 14 percent, respectively [10]. Among these patients, adherence rates were lower among younger, male patients and those who were prescribed diuretics or more than one antihypertensive medication.

●Based upon an analysis of United States health insurance claims in combination with a National Health Interview Survey of 24 million adults with hypertension, 31 percent were nonadherent to antihypertensive therapy [11]. Nonadherence rates varied according to multiple factors:

•Insurance plan (from 25 percent with Medicare Part D to 55 percent with Medicaid)

•Age (from 24 percent among those aged 65 to 74 years to 58 percent among those aged 18 to 34 years)

•Use of a fixed-dose combination pill (29 percent compared with 31 percent among those not using fixed-dose combinations)

•Pharmacy type (20 percent among those using a mail-order pharmacy versus 31 percent with a retail-only pharmacy)

While nonadherence contributes to the burden of uncontrolled hypertension, approximately 65 percent of patients in the United States who report taking antihypertensive medications had blood pressure controlled to <140/<90 mmHg [12]. Thus, while the majority of treated patients are taking sufficient medication to control their hypertension to that level, many patients have a lower blood pressure goal based on cardiovascular risk. (See "Goal blood pressure in adults with hypertension".)

FACTORS AFFECTING TREATMENT ADHERENCE — Suboptimal adherence is a major barrier to realizing the benefits of evidence-based pharmacologic therapies for many conditions, and nonadherence remains a key barrier to better patient outcomes [13]. Adherence is a complex phenomenon, and no single intervention has solved this challenge.

The World Health Organization (WHO) has identified five dimensions of adherence [14]:

●Social and economic factors such as age, race, sex, socioeconomic and educational status, and quality of health care insurance.

●Patient-related factors, including readiness to change; locus of control and self-efficacy; health beliefs; health literacy; use of alternative therapies; forgetfulness; fear of dependence; and future discounting, in which patients ascribe less value to long-term benefit of chronic disease management [15,16].

●Therapy-related factors including the complexity and cost of treatment, especially out-of-pocket costs, and adverse effects

●Comorbid conditions, such as drug and/or alcohol abuse, depression, psychosis, or impaired mental status; the number of coexisting chronic medical conditions; and severity of symptoms

●Health care system factors, such as the patient-provider relationship, provider workload and burnout, misaligned and absent incentives, and absent or limited care coordination and care integration

Additional factors have also been found to reduce adherence with antihypertensive therapy (table 1).

Patient and disease characteristics — Patients with hypertension have special problems related to the nature of their disease.

●A substantial minority of hypertensive individuals are largely unaware of the definition, possible causes, sequelae, and therapeutic needs of hypertension. A variety of factors may contribute to the lack of awareness, such as the following:

•Most hypertensive individuals are asymptomatic, and therefore they frequently have little motivation to seek or follow treatment.

•Hypertension often begins prior to the age of 40 years when many individuals, especially males, receive minimal preventive health care [17]. The prevalence of early onset of hypertension is increasing as the adiposity of the population increases. Not surprisingly, hypertension control is lower at these younger ages, especially in men.

●Patients with hypertension rarely present only with hypertension. Rather, multiple chronic conditions are often present including hyperlipidemia, obesity, diabetes, arthritis, depression, and gastroesophageal reflux. In Medicare beneficiaries with hypertension and related complications, the burden of comorbid disease is particularly high [18].

●In some patients, recognition of hypertension or other chronic disease diagnosis may provoke a denial reaction. In addition, the diagnosis of hypertension carries potential economic and social threat for some individuals (eg, job loss, insurance, and sexual potency), which may further inhibit the patient from accepting the diagnosis and effective treatment.

Treatment challenges — The treatment of hypertension raises several adherence challenges, including the use of complex and costly regimens that may have adverse effects [19].

Side effects of antihypertensive medications are common and may discourage adherence. Examples include impotence and overt or subtle effects on mood and psychologic functioning [20]. The latter findings may only be identified by careful questioning and testing.

In addition, achieving adequate blood pressure control often requires using more than one medication [21-23]; such a medication regimen with multiple pills may contribute to decreased adherence [24,25].

ASSESSMENT OF ADHERENCE — Although most clinicians are confident that they can predict the antihypertensive medication adherence of their patients, their predictions are no more accurate than what can be obtained by the toss of a coin [26]. No single method is both practical and highly accurate. Attempts to identify the sociodemographic and clinical variables associated with increased adherence have produced variable results [27].

There are several feasible and potentially useful options to assess adherence in the routine clinical setting; examples include [28-30]:

●Discuss adherence – Ask the patient if they miss any doses of antihypertensive medication. Patients who admit to missing doses are typically taking fewer than 80 percent of prescribed doses, although some more adherent patients may admit to missing an occasional dose [31]. The likelihood of nonadherence is even greater if, in addition to acknowledging missing doses, there has been a poor blood pressure response to antihypertensive medication.

●Identify barriers – Use a simple questionnaire. As an example, one published questionnaire contains just three items: the degree to which the patient feels the medication is important, the degree to which the patient thinks the medication may harm them, and the degree to which the medication is financially burdensome [29]. The individual responses are scored and added, producing a likelihood of adherence problems ranging from greater than 68 percent to less than 25 percent (table 2). The Morisky Medication Adherence Scale (MMAS-4) is another commonly used tool to estimate the likelihood of nonadherence [1].

●Employ pill counting – Ask the patient to bring his or her antihypertensive medications to the office visit and calculate the medication possession ratio (MPR), which serves as a proxy for adherence [30]. This involves reviewing the prescription bottles at an office visit and checking the number of remaining refills relative to when the prescription was first filled. In this way, the clinical staff can estimate days of supply or the MPR as a proxy for adherence. As an example, if a 90-day supply of medication was initially prescribed with three refills (360 days of available medication) and after nine months the medication bottle indicates that there are two refills remaining, then only 180 days of medication were filled over a 270-day period. The MPR is 180/270 or 0.67. Most patients do not refill prescriptions for medications that they are not taking, especially if filling those prescriptions requires personal effort and out-of-pocket cost.

However, these methods are imperfect and sometimes fail to identify nonadherent patients. As an example, in one study that measured urinary drug metabolites, complete nonadherence was identified in approximately 25 percent of patients who underwent a detailed evaluation for resistant hypertension and who, based upon detailed questionnaires, were believed to be taking all prescribed antihypertensive medications [32]. A similar study compared adherence assessed using directly measured drug metabolites with responses to the MMAS-4 questionnaire [33]. Scores on the MMAS-4 were similar among adherent and nonadherent patients.

More sophisticated techniques for assessing adherence include measurements of medications in urine or blood samples [34,35], electronic medication monitors, and the use of pills that emit a small electrical signal triggered by gastric acid that are detected by an abdominal sensor [36]. While the technology for this last technique is at an early stage, the potential for assessing adherence would be even better than with pill bottle memory caps, which simply detect whether the prescription bottle was opened. However, these options are not available for routine clinical practice [37] and may not be feasible in primary care.

Among patients with apparent treatment-resistant hypertension, suboptimal medication adherence may be a significant contributor to inadequate blood pressure control. The American Heart Association (AHA) statement on treatment resistant hypertension recommends measuring antihypertensive drugs or their metabolites in plasma or urine [38]. Urine drug screens for diuretics are widely available and typically detect one or more subclasses, including thiazide-type, loop, and potassium-sparing diuretics as well as mineralocorticoid receptor antagonists and carbonic anhydrase inhibitors. Hydrochlorothiazide is included in many single-pill combinations with one or two other medication classes, and in such settings, its presence in urine provides a measure of at least partial adherence to the combination. Objective documentation of nonadherence has led to significant improvements in both adherence and blood pressure control among adults with uncontrolled and apparent treatment-resistant hypertension [39-41].

METHODS TO IMPROVE ADHERENCE — Guidelines to improve patient adherence are listed in the table (table 3). A few of these suggestions deserve more emphasis.

Educate and communicate — Educate and maintain contact with the patient and the patient's family [42]. Information about medications, when written in simple language and attractively presented, is useful [43]. Broken appointments to clinics have been reduced by mail, telephone, and clinician reminders and by establishing a contract with the patient [44,45].

Clinicians who provide more information to patients generally achieve better patient satisfaction, recall, and adherence [45,46]. Clinicians who interview patients with questions that encourage the patient to reflect on the consequences of their behavior appear to achieve better patient satisfaction, recall, and adherence than those who use more direct or close-ended questions [47].

Shared decision making — Patients who are actively engaged in selecting their treatments (ie, shared decision making) are more likely to adhere to treatment than patients for whom the clinician is the sole decision maker [48]. In the United States, there are population disparities in the rates of shared decision making, with Black and Hispanic patients less likely than White patients to be involved; this may impact variations in adherence rates [49].

Team-based approach — Interdisciplinary team-based care has been identified as a strategy for improving hypertension control [50]. Patients receiving care for chronic diseases, including hypertension, had better medication adherence when receiving their care through a patient-centered medical home [50,51]. In addition, integration of community health worker-based interventions into a team-based care system improved medication adherence [52].

Encourage home blood pressure self-monitoring — Some reports have shown that home blood pressure self-monitoring can improve adherence, especially among patients with uncontrolled hypertension [53,54]. The impact of self-monitoring on blood pressure control, and presumably adherence, improves if blood pressure data are relayed back to the health care provider and improves further if the health care provider then communicates back to the patient between visits.

Use technology acceptable to the patient — Various patient-reminder systems exist to improve adherence, ranging in sophistication from pill organizers to daily pill dispensers and text messaging [55,56]. As an example, in a pooled analysis of 16 randomized trials and more than 2700 hypertensive patients (mean age of 39 years), the use of text messaging reminders nearly doubled the likelihood of medication adherence [56].

Keep treatment inexpensive and simple — An effort should be made to limit both the financial burden and complexity of antihypertensive therapy:

●Reduce out-of-pocket costs – Adherence is inversely related to out-of-pocket medication costs. In one study, for example, out-of-pocket costs accounted for 36 percent of the variance in adherence [57]. Thus, efforts to minimize out-of-pocket costs, especially for relatively asymptomatic conditions such as hypertension, are important. (See "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)".)

The use of less expensive medications is being emphasized to reduce the costs of health care and to ensure that patients have access to needed medications without undue cost barriers. Generic, less expensive options are now available within each class of antihypertensive drugs. Studies of blood pressure-lowering drugs indicate that adherence may be better with generic as compared with proprietary formulations [58,59].

●Use the lowest effective dose – Minimum effective doses should be prescribed in an attempt to avoid or limit side effects of antihypertensive medication. In general, approximately 80 percent of the blood pressure lowering effect of antihypertensive medications occurs at standard doses or half of the maximum recommended dose [60]. Doubling the standard dose often produces limited additional decline in blood pressure yet raises the potential for adverse effects.

●Use single-pill combinations – Keeping therapy simple includes the use of single-pill combinations that contain more than one antihypertensive medication (eg, lisinopril-hydrochlorothiazide, valsartan-hydrochlorothiazide, azilsartan-chlorthalidone, telmisartan-amlodipine, valsartan-amlodipine, and olmesartan-amlodipine-hydrochlorothiazide, among others) (table 4). Furthermore, most medication classes are available in once-a-day formulations so that fewer tablets are needed [61].

Several studies have shown that patients receiving single-pill antihypertensive combinations are more likely to adhere than patients given the same medications as individual pills [24,25,62,63]. Patients given single-pill combinations also appear to achieve control more rapidly and to attain better control during the first 6 and 12 months of treatment [63-65]. Moreover, single-pill combinations can reduce cardiovascular events and death [66].

Therapeutic inertia also appears to be lower with single-pill combinations than traditional stepped-care therapy using single-pill medications [67].

Consolidate refills — Many patients with hypertension have multiple chronic conditions and receive a substantial number of prescription medications. Reducing the number of visits to the pharmacy required to fill their polypharmacy regimens by consolidating and coordinating refills can improve adherence [68].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Coping with high drug prices (The Basics)" and "Patient education: Side effects from medicines (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Importance of adherence with hypertension treatment – Suboptimal adherence with prescribed antihypertensive medication and lifestyle changes contributes to the burden of uncontrolled hypertension.

●Factors affecting treatment adherence – In patients with hypertension, many factors have been found to reduce adherence (table 1) (see 'Introduction' above and 'Factors affecting treatment adherence' above):

•Patient and disease characteristics, such as lack of awareness (because, for example, patients are asymptomatic); the burden of comorbid conditions; and the economic and social costs of treatment. (See 'Patient and disease characteristics' above.)

•Treatment challenges, such as the complexity, cost, and side effects of therapy; in addition, communication between patient and clinician about these issues is frequently suboptimal. (See 'Treatment challenges' above.)

●Assessment of adherence – Adherence may be assessed in the clinical setting with the following (see 'Assessment of adherence' above):

•Ask the patient if they miss any doses of antihypertensive medication. Patients who admit to missing doses are typically taking fewer than 80 percent of prescribed doses.

•Use a simple three- or four-item instrument to assess the likelihood of adherence (table 2).

•Review the prescription bottles at an office visit and check the number of remaining refills relative to when the prescription was first filled. In this way, the clinical staff can calculate the ratio of days of obtained medication (supply) divided by the days in the treatment period.

However, these methods are imperfect and sometimes fail to identify nonadherent patients. In patients with apparent refractory hypertension, laboratory testing or electronic medication monitors may be used to assess adherence.

●Methods to improve adherence – There are guidelines to improve patient adherence with treatment (table 3). As examples (see 'Methods to improve adherence' above):

•Educate and maintain contact with the patient and the patient's family. (See 'Educate and communicate' above.)

•Engage patients in selecting their treatments (ie, shared decision making). (See 'Shared decision making' above.)

•Employ interdisciplinary team-based care, including patient-centered medical home. (See 'Team-based approach' above.)

•Encourage home blood pressure monitoring. (See 'Encourage home blood pressure self-monitoring' above.)

•Use a patient-reminder system, such as pill organizers, daily pill dispensers, or, if technologically acceptable to the patient, text messaging. (See 'Use technology acceptable to the patient' above.)

•Limit both the financial burden and complexity of antihypertensive therapy, including the use of single-pill combinations (table 4). (See 'Keep treatment inexpensive and simple' above.)

•Reduce the number of visits to the pharmacy required for polypharmacy regimens by consolidating and coordinating refills. (See 'Consolidate refills' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman Kaplan, MD, who contributed to an earlier version of this topic review.