Source: American Heart Association
The global epidemic of hypertension is largely uncontrolled and hypertension remains the leading cause of noncommunicable disease deaths worldwide. Suboptimal adherence, which includes failure to initiate pharmacotherapy, to take medications as often as prescribed, and to persist on therapy long-term, is a well-recognized factor contributing to the poor control of blood pressure in hypertension. Several categories of factors including demographic, socioeconomic, concomitant medical-behavioral conditions, therapy-related, healthcare team and system-related factors, and patient factors are associated with nonadherence. Understanding the categories of factors contributing to nonadherence is useful in managing nonadherence. In patients at high risk for major adverse cardiovascular outcomes, electronic and biochemical monitoring are useful for detecting nonadherence and for improving adherence. Increasing the availability and affordability of these more precise measures of adherence represent a future opportunity to realize more of the proven benefits of evidence-based medications. In the absence of new antihypertensive drugs, it is important that healthcare providers focus their attention on how to do better with the drugs they have. This is the reason why recent guidelines have emphasize the important need to address drug adherence as a major issue in hypertension management.
The global burden of hypertension, defined as blood pressure (BP, mm Hg) ≥140 systolic or ≥90 diastolic or antihypertensive treatment, was projected to rise from 918 million adults in calendar year 2000 to 1.56 billion in 2025.1 The projected increase in the burden of hypertension reflected an expected rise in both prevalent hypertension from 26.4% to 29.2% and the worldwide population. By 2010, these projections appeared conservative as the worldwide prevalence of hypertension was estimated at 31.1%, affecting 1.39 billion people.2 The large increase in prevalent hypertension globally was explained largely by rapidly rising prevalence in low-middle–income countries. In 2010, ≈349 million hypertensive adults lived in high-income countries and 1.04 billion in low-middle–income countries. Prevalent hypertension was lower in high- than low-middle–income countries, whereas awareness, treatment, and control were substantially lower in the latter (Table 1). Among treated hypertensive adults, roughly one-half were controlled in high-income countries compared with one-fourth in low-middle–income countries.
Assuming clinically valid BP values, 2 major factors contribute to hypertension control in treated patients; namely, prescription of an adequate number and dose of prescribed BP medications and adherence with therapy. This review focuses on patient adherence as a critical variable in BP control. Insightful statements with timeless truth include “Drugs don’t work in patients who don’t take them”3; and “the full benefits of medications cannot be realized at currently achievable levels of adherence.”4
Adherence with pharmacotherapy for hypertension 1-year after initiation is typically reported at below 50%.5,6 The proportion of treated patients controlled, historically ranging from 20% to 50% (Table 1),2,7 reflects both effectiveness of pharmacotherapy prescribed and adherence with treatment. Using the proportion of treated patients controlled as a proxy for adherence, data that are more recent suggest that adherence has been improving, at least in some countries. For example, in the United States, ≈70% of treated patients have been controlled to below 140/90 since 2007 to 2008,8 a level achieved in Germany during 2008 to 2011.9 In Canada, an extraordinary 85% of treated patients were controlled in 2013.10
Hypertension control in Canada rivals many clinical trials, which typically exclude patients with comorbidities such as drug or alcohol abuse or dementia, factors that adversely impact adherence and control.11 In clinical trials, the treatment protocol is rigorous, clinical visits are relatively frequent and physicians and patients are motivated to reach protocol objectives. Thus, in a review of 192 studies in which pill count was used to assess adherence, drug adherence was found to be 93%.12 But more recent data suggest that even in clinical trials nonadherence can affect a substantial percentage of the participants.13 Consistent adherence is a key to sustained BP control, which, in turn, influences clinical outcomes. For example, in the INVEST (International Verapamil SR-Trandolapril trial), the greater the number of clinical visits with a nonhypertensive BP, the lower the incidence of clinical outcomes.14
In the United States, the large improvement in hypertension control over time coincides with a greater number of antihypertensive medications prescribed per patient.15 Over time, the proportion of uncontrolled hypertensives in the United States with Stage 2 disease (BP ≥160 systolic or ≥100 diastolic) has declined,16 which suggests adherence improved in some patients not at goal BP, although one cannot exclude an impact of better BP measurement methods. The observations cited suggest that adherence is improving with time and that prior studies on adherence may be less valid currently. Yet, a substantial proportion of adults remains uncontrolled, even in countries with the highest control rates. Of greater concern are the large numbers of adults in low-middle–income countries, with uncontrolled hypertension, who continue to have a relatively low proportion of treated adults at goal BP levels (Table 1).2 Indeed, the survival of a treated hypertensive patient not at goal is similar to that of an untreated hypertensive patient suggesting that a lot of efforts are made for little benefits.17
The impact of suboptimal adherence, a key contributor to uncontrolled hypertension, will be addressed in greater detail subsequently. In brief and from a global perspective, there were ≈56.4 million deaths in 2015. Approximately 70% of deaths worldwide were attributed to noncommunicable diseases including hypertension with 75% of those deaths occurring in low-middle–income countries (noncommunicable disease mortality and morbidity). Global Health Observatory data: http://www.who.int/gho/ncd/mortality_morbidity/en/ (accessed August 16, 2018). Cardiovascular diseases accounted for 45% of deaths because of noncommunicable diseases with uncontrolled hypertension the major risk factor.
In the present review focused on adults with hypertension, we shall (1) define suboptimal adherence and persistence, (2) examine the methods for detecting suboptimal adherence and its prevalence in treated hypertensive patients including those with treatment resistant hypertension, (3) identify contributing and associated factors, (4) describe the health and economic impact of suboptimal adherence, and (5) provide practical guidance for improving adherence.
Many definitions of compliance or adherence can be found in the literature before the World Health Organization (WHO) published the first official definition of adherence in 2003.7,18 In contrast to previous ones, it was not restricted to drug therapy and included all aspects of disease management such as diet and lifestyle changes. Thus, adherence was defined as the extent to which a person’s behavior-taking medication, following a diet, and executing lifestyle changes, corresponds with agreed recommendations from a health care provider. In 2009, a consensus meeting on adherence was held that gathered together 80 persons of various professional horizons but all involved in patients’ care with medications. This consensus meeting resulted in a new taxonomy published in 2012.19 In this publication, the authors differentiate the processes, such as adherence to medications and the management of adherence, from the discipline studying these processes, that is, the adherence-related sciences. According to this consensus, adherence to medications is a process characterized by 3 major components: the initiation, the implementation, and the discontinuation. Initiation is the time from prescription until the first dose of the medication is taken. In clinical studies, 4% to 5% of patients never start their treatment, despite the fact that they accepted to be enrolled in a study.5 In clinical practice, noninitiation seems to be much more frequent with figures 20% in patients treated for hypertension but also in those treated for diabetes mellitus or dyslipidemia.20 However, this phenomenon may vary considerably depending on the countries and the access to medications.
The implementation of the dosing regimen is the extent to which a patient’s actual dosing corresponds to the prescribed dosing regimen. This component of adherence is best assessed using methods providing a complete dosing history, and hence, tackling the day-to-day variations in drug intake.19 A poor implementation is the typical consequence of occasional forgetfulness or negligence resulting in more or less prolonged periods of treatment interruptions. These latter may be intentional or nonintentional, but in the majority of cases, there is no clear intention of patients to omit their medications. When the dosing history is available, additional parameters of implementation can be defined and quantified. This includes the proportion of prescribed drug taken, the proportion of days with a correct number of doses taken (taking adherence), the proportion of doses taken on time respecting the dosing intervals (timing adherence) and the number of drug holidays as intervals of time when a patient temporarily stops taking the medications. Yet, it is not possible to define drug adherence quantitatively with a given threshold below which a patient can be considered as poorly adherent. Indeed, although an arbitrary cutoff of 80% is frequently used in the literature to define a good adherence, there is little evidence, if any, that this cutoff is relevant.21 Indeed, 80% adherence is obtained in many ways as illustrated in Figure 1 and these different profiles may have different consequences in terms of clinical impact. In this context, the pharmacological profile of the prescribed drugs, in particular the duration of action, is a major determinant of the impact of missed doses on BP control.22 In addition, the clinical consequences of missed doses may differ in patients with mild hypertension and those with severe resistant hypertension, for example.
At last, discontinuation marks the end of therapy, when the next dose to be taken is omitted and the treatment is interrupted thereafter. This parameter enables the definition of persistence, which is the length of time between initiation and the last dose immediately preceding discontinuation. Nonpersistence is one of the most common cause of poor adherence in hypertension with 50% of patients having stopped their treatment at 1 year.5 It is particularly prevalent among newly treated hypertensive patients,23,24 and the risk of discontinuation seems to be higher among patients aged below 40 years.25 The choice of drug classes prescribed for the treatment of hypertension also has an impact on adherence and persistence due essentially to the side effect profile,23,26,27 although the dosing frequency may play as much a role as the drug class itself.28 Obviously, a lack of persistence has a major influence on BP control as patients remain off medication for long periods.
In recent years, the use of large computerized administrative health databases containing pharmacy or medical data are becoming increasingly common and represent new sources of medical evidence.29,30 These databases enable assessment of drug prescriptions as well as the utilization patterns and drug persistence in large groups of patients. Although they do not provide a precise dosing history, these databases give information on medication prescription, initiation, and refills during a defined period enabling calculation of drug persistence.25,31 Sometimes, these data can also be correlated to the occurrence of events such as death or cardiovascular events. Using this approach, the main parameters that are generally calculated are the percentage of days covered by the prescriptions32 or the medication possession ratio, defined as the ratio of total days of medication supplied to total days in a defined time-period. It is also possible to calculate the new prescription medication gap, a metric that starts with the date of prescription and includes the time until initiation, which is not the case with the medication possession ratio.33
In the WHO 2003 Report, Adherence to long-term therapies: Evidence for action,18 it was noted that “The ability of patients to follow treatments is frequently compromised by more than one barrier… Interventions to promote adherence require several components to target these barriers, and health professionals must follow a systematic process to assess all the potential barriers.” While the literature on adherence has advanced during the past 15 years, the 5 dimensions of adherence in the 2003 Report remain useful (Table 2). A conceptual understanding of these 5 dimensions can inform a more comprehensive assessment of factors contributing to suboptimal adherence as a prelude to the design, implementation, and refinement of effective, multicomponent interventions to realize more health benefits of antihypertensive therapy.
Several factors in this group, many of which are listed in Table 2, are associated with suboptimal adherence.6,7,11,34 However, not all of these factors, such as age, income, and race-ethnicity, are consistently related with adherence across all studies. Attempts have been made to derive clinically useful predictors of adherence by combining several sociodemographic and clinical variables, which are significantly different between adherent and nonadherent patient groups. However, a composite score developed from a basket of these variables may not provide clinically useful discrimination even for individuals from which the predictive model was developed.35 A more effective strategy may be to use reliable methods to detect suboptimal adherence in specific patients and then to identify the specific factors in this dimension rather than designing systems that provide solutions for all patients with barriers in this category, when many are adherent. This statement is not intended to minimize the very real challenges to adherence presented by individuals experiencing various sociodemographic, economic, and environmental barriers but rather to indicate that many individuals are adherent, despite the barriers.
Hypertension control in uninsured and privately insured adults over time is one indirect example of the limited prediction of outcomes from 3 generally recognized predictors of adherence. Publicly and private insured adults in the United States had virtually identical BP control from 1988 to 2010,36 which included a roughly 22% absolute improvement in control over that time period. However, the publicly insured group had a larger proportion of racial-ethnic minorities with lower incomes and less education than the privately insured, 3 factors often cited as predictors of suboptimal adherence.
The quality of the relationship between the patient and clinician, the communication style of the clinician, and the patient-centeredness of treatment decisions all impact adherence.6,7,11,34,37,38 Trust is the critical currency in most human interactions and this applies especially to healthcare. The patient must have confidence that their clinician is competent and has their best interests foremost in management decisions. A collaborative communication style and communication that includes circular and reflexive questions are more effective than a lineal and strategic inquisition style akin to a witness being cross-examined by an attorney. Thus, ‘did you take your medication(s)?’ or ‘why don’t you follow a low-salt diet?’ is less effective that ‘are you having any problems with your medications such as they’re too costly or cause unpleasant adverse effects?’ or ‘how does a low-salt diet affect you?’ or ‘what are some of the difficulties you have with a low-salt diet’?
Patients that participate in decisions on what medications to take are more adherent than patients who are not engaged in the decision.39 Racial-ethnic minorities are less often engaged in decision on their treatment than white adults, which may be a contributing factor to lower adherence in the former.40 Team-based care and well-functioning patient-centered medical homes are associated with better adherence and risk factor control than when these factors are not present.41,42 In addition to suboptimal communication, overworked and burned out clinicians can adversely impact the adherence of their patients. Clinicians and staff are generally happier and more productive in an effective team-based care arrangement, and, clinician burnout is reduced.42 Often times, clinicians and staff fail to recognize key clues linked to suboptimal adherence such as missed appointments or prescription refills or poor therapeutic response to medications or combinations of medications that are almost always effective.43
Practice settings without adaptive reserve in which clinicians, staff, and administration expend all their time and energy working to get through the day and complete all documentation and billing requirements are not positioned to implement constructive changes to improving patient care, adherence, and outcomes.44 Practice settings with adaptive reserve in which high-quality care is valued and time, resources and reports are available to support quality improvement are positioned to enhance patient engagement, adherence, and outcomes.
Access to and cost of care and medications are clearly important in clinical outcomes and adherence.6,7,11,18,34,45 Uninsured adults in the United States experienced no significant improvement in hypertension control between 1988 and 2010, whereas a demographically similar group with public (government)-sponsored health insurance had virtually identical control to a more affluent and better educated group with private health insurance.36 As noted both insured groups had a roughly 22% absolute improvement in hypertension control during this time-period in sharp contrast to no improvement in uninsured adults. Moreover, healthcare payment directed mainly to volume of care and clinical documentation, which was the standard in the United States is a barrier to supporting patient adherence and key clinical outcomes. For example, a study in the 1970s showed that reallocating some time spent in documenting variables toward patient education and support improved adherence to antihypertensive medications and BP control.45
Complex regimens with multiple medications, especially when paired with multiple daily doses, are long-recognized as barriers to adherence.6,7,11,18 Alternatively, fewer medications, and especially fewer pills, which can be implemented using once daily single-pill combinations are consistently associated with better adherence and hypertension control.45,46 Patients who reach therapeutic targets more rapidly, who require fewer adjustments in their medication regimen, and who experience no or limited adverse effects are more likely to adhere than patients with a longer period to control, who often undergo multiple changes to their medication regimens, and experience adverse effects, are less likely to adhere to treatment.6,7,11,18 Long-term chronic diseases, such as hypertension, are often associated with progressive declines in persistence on treatment with the passage of months and years.47,48
In addition to single-pill combinations, clinicians can further improve adherence by prescribing a larger number of pills with each prescription to reduce refill frequency.49,50 Moreover, patients with hypertension often require multiple medications to control their hypertension, and they frequently have other chronic diseases requiring additional medications. Refill consolidation so that multiple medications are obtained at the same time can improve adherence.51
Adults with hypertension, especially with aging, often have multiple chronic conditions and polypharmacy, which may adversely affects medication adherence. Major depression and other psychoses can adversely influence adherence as can drug or alcohol abuse and dementia.52,53 Interestingly, alterations of memory in elderly patients can results in a poor adherence as well as in an overadherence, with a higher drug consumption than what has been prescribed, which may induce drug toxicity.54 Not surprisingly, major disabilities and poor quality of life are documented to adversely affect medication adherence,55 especially when the medication(s) do not attenuate the disability or enhance quality of life. On a related note, severe chronic symptomatology, similar to chronic asymptomatic disease,56 can adversely impact medication adherence.
As noted in the 2003 WHO Report on adherence, patient-related factors are often the principal focus of efforts to understand and improve adherence, which can lessen attention to the important role played by the other dimensions of adherence.18 While most interventions center on patient-related factors can improve adherence, failure to account for other dimensions of adherence typically leads to suboptimal improvements in adherence and associated clinical outcomes. To highlight the importance of these other dimensions, patient-related factors, which are important, were presented last in the 2003 WHO Report and the current review.
Some patients do not accept the diagnosis, which is obviously a major impediment to adherence. While not denying the diagnosis, other patients may fail to perceive the potentially severe impact of a currently asymptomatic disease on future health risk, including symptomatic and life-threatening conditions, such as coronary heart disease, chronic heart failure, stroke, or dementia. If patients perceive that prescription medications are ineffective in controlling hypertension or are likely to have major adverse effects, then adherence is likely to be adversely impacted. A lack of knowledge about hypertension and its consequences are logically linked to suboptimal adherence. Yet, adherence interventions based only on education often lead to suboptimal results,6,7,11,18,34,57 although education is often a component of successful multimethod interventions. One example of a common misunderstanding that adversely affects adherence is the term hypertension, which connotes too many patients that stress or behavioral issues are the root cause of the elevated BP.58 In fact, patients with this perception of hypertension are less likely to take antihypertensive medications.
Forgetfulness is a common contributor to suboptimal adherence, a conclusion supported by evidence that multimethod interventions, which improve adherence often address this barrier.1–5 Low self-efficacy, or lacking confidence in one’s ability to self-manage effectively a condition or disease, is another frequently documented barrier to adherence.6,7,11,18,34,59
Patients who use alternatives to traditional or Western medicine are less likely to adhere with prescription medications.60,61 Preference for alternative therapies appears to be more common among black than white adults in the United States and may contribute to lower adherence in the former.62
Less well appreciated and investigated is the issue of future discounting. Individuals who discount the future at higher rates appear less likely to engage in preventive health behaviors including taking medications for chronic conditions, although additional research is needed.62–64 In other words, understanding that hypertension is a serious condition and that treatment is effective may be insufficient to foster adherence if the patient believes that the consequences will occur at a future date, for example, 5 years or more, that does not have value today.
Multiple lines of evidence indicate that adherence is a complex, multidimensional variable. The WHO 2003 Report provides a useful conceptual model (Table 2) for grouping the multiple variables that impact adherence.18 This conceptual model can serve to inform effective approaches for identifying nonadherence as well as designing, evaluating, and revising interventions to enhance adherence.
In chronic diseases where medication primarily serves as a preventive measure, and not to suppress symptoms, maintaining long-term adherence is particularly difficult, and the risk of treatment discontinuation is very high. Thus, among various cardiovascular medication classes, prescriptions of antihypertensive and lipid lowering drugs have the highest rates of noninitiation.65 In addition, in these clinical conditions, only about half of the patients remained on therapy after 2 years.23,66 Of interest, Naderi et al67 have found similar low figures in the 50% range in primary as well as in secondary cardiovascular prevention. Thus, in real life, prolonged discontinuation of antihypertensive therapies is extremely common as shown by Corrao et al23 who analyzed the Lombardy database.
Though poor adherence is recognized as a major contributor of uncontrolled hypertension in surveys, meta-analyses and clinical practice guidelines, detection of suboptimal adherence remains a major challenge for all physicians and healthcare partners. Indeed, as of today, there is no simple, cheap, reliable methods to assess medication adherence in clinical practice. As illustrated in Table 3, simple methods tend to be relatively unreliable, and methods providing the best information tend to be more expensive and demanding in terms of infrastructures. The ideal method to assess drug adherence should provide a reliable capture, storage, analysis, and communication of dosing history data in ways that make it difficult or impossible for patients or trial staff to censor or otherwise manipulate the data.21 As of today, none of the available systems fulfills all these criteria.
The adverse impact of suboptimal adherence to antihypertensive medications is multi-fold (Table 4), and the untoward economic impact potentially large.
While the table may be perceived as splitting categories of adverse outcomes, it is important to recognize the broad impact of inadequately or untreated hypertension that can result from suboptimal adherence to effective prescription medications. Hopefully, the list will serve to raise the value of adherence from the perspective of clinicians and the patients they serve as well as healthcare payers and policy makers as integrative approaches are required to optimize adherence. There is, however, a caveat. Before amplifying items in Table 4, it is important to recognize the potential for overestimating the adverse effects of nonadherence. Evidence suggests that differences beyond BP reduction or hypertension control between more and less adherent patients may account for a substantial proportion of variance in adverse outcomes.7,144–146 For example, more adherent patients appear to generally have a more positive attitude toward preventive health measures, which could favorably impact multiple outcomes.7,144
The literature documents the multiple adverse clinical consequences of suboptimal adherence. The adverse effects include uncontrolled hypertension and hypertensive crises. Suboptimal adherence is also associated with various target organ changes linked to a greater risk of cardiovascular events, including vascular stiffness, left ventricular hypertrophy (LVH), and microalbuminuria. Suboptimal adherence is also associated with multiple adverse cardiovascular events including acute coronary syndromes, stroke and transient ischemic attack and chronic heart failure as well as mortality.
Evidence supports the notion that patients with controlled hypertension are more likely to adhere to antihypertensive pharmacotherapy than are individuals with uncontrolled BP.116,117 Conversely, patients staying on therapy are more likely to achieve long-term BP targets.118
Several of the initial randomized, double-blind, placebo-controlled studies in hypertension showed that treating hypertension reduced progression to more severely elevated levels of BP as well as accelerated and malignant hypertension.147,148 In a similar vein, more recently reports found that poor medication adherence was linked with the occurrence of hypertensive crises.119
Greater vascular stiffness, as measured by arterial pulse wave velocity, was associated with a clinically and statistically significant increase in the first occurrence of a major cardiovascular event (composite myocardial infarction, unstable angina, heart failure, or stroke).149 Low adherence to antihypertensive medications, in turn, was associated with increased arterial stiffness derived from 24-hour ambulatory BP monitoring.120
Incident LVH by electrocardiography did not occur in either black or white adults with hypertension during the 5 years of stepped-care therapy in the Hypertension Detection and Follow-Up Study. However, in the 7 years of follow after completing stepped-care therapy, LVH was a relatively common occurrence, especially among black adults.121 The authors noted specifically that adherence to antihypertensive medications declined substantially among black men during the follow-up period and viewed that fact as contributing to incident LVH. In another report, LVH by electrocardiography was significantly associated with poor adherence to antihypertensive medications before stroke among patients that suffered an acute stroke.122
Among 40 473 Korean adults with hypertension, 2657 had urine albumin/creatinine ≥30 μg/mg including 499 with values ≥300 μg/mg. Low adherence to antihypertensive medications was independently associated with the presence of albuminuria.123
In view of the association of poor adherence with uncontrolled hypertension, hypertensive crises, and several risk factors for cardiovascular disease, the association of suboptimal adherence with major adverse cardiovascular events is expected.124–130 Some reports included very large numbers of patients such as a meta-analysis with 1 978 919 unique patients and the Italian Lombardy Region with 242 594 newly treated hypertensives.125,126 Moreover, suboptimal adherence has also been associated with individual components of composite cardiovascular disease, including myocardial infarction, stroke, and chronic heart failure.127,128,131
Suboptimal adherence to medications generally is associated with faster progression of chronic kidney disease.132 Moreover, suboptimal adherence to antihypertensive medications specifically is independently linked to greater risk for incident end-stage renal disease.133
Cognitive dysfunction and dementia are well-recognized causes of poor adherence in elderly patients53,54 because they impair the abilities in planning, organising, and executing medication management task. Because BP control plays a role in the prevention of cognitive dysfunction and dementia,134 a good adherence to antihypertensive should be favorable. Studies have demonstrated that it is possible to improve drug adherence in patients with cognitive dysfunction or dementia, but none has really demonstrate a clear impact on the reduction of health outcomes.135
The US National Hospital Ambulatory Medical Care Survey for 2005 to 2007 indicated that ≈13% of emergency department admissions were related to medication nonadherence. The likelihood of emergency department visits for hypertension was strongly related to nonadherence.136,137 In addition, 20% of emergency department admissions associated with nonadherence led to hospital admission compared with 12.7% unrelated to adherence. Other reports confirm that adults with suboptimal adherence to antihypertensive medication have more hospital admissions for cardiovascular-related events.127,137
More intensive hypertension control to BP values below 140/90 was associated with more serious adverse events attributable to more intensive therapy or lower BP levels.150,151 Yet, other data indicate that better hypertension control and greater adherence to BP medications are associated with a higher quality of life.138
Ischemic heart disease was the leading cause of disability-adjusted life-years in the US during 1990 and 2016 with stroke 10th in 1990 and 12th in 2016.139 Uncontrolled hypertension is a major contributor to both events. Self-reported low adherence to antihypertensive medication was linked to higher levels of work impairment and presenteeism, that is, individual present but less productive.140
In the United States, suboptimal adherence is estimated to account for up to 10% of total healthcare costs.141 With regard to adherence and hypertension, among employees of a large manufacturer and their dependents below 65 years old,142 hypertension-related healthcare costs were lower for individuals with 80% to 100% at $4871/y than the 4 groups with lower adherence (range $4878−$6062/y). Similarly, total healthcare costs for hypertensive adults with high adherence ($8386) were lower than for the other 4 lower adherence groups ($8929−$11 238). In another report,143 data on 112 757 hypertensive patients were obtained from a large pharmacy benefit manager. Annual medication costs were $429 greater for patients with high than low adherence but were associated with $3908 lower annual medical expenditures.
Analysis of large claims database indicated that mean annual healthcare costs were lower for hypertensive patients with 80% to 100% adherence to BP medications ($7182, n=467 006) than for patients with 60% to 79% adherence ($7560, n=96 226) and below 60% adherence ($7995, n=62 338).137 Patients with moderate and low adherence were more likely to have emergency department and hospital admissions for cardiovascular conditions than those with high adherence.
In a model derived from observational data, both ideal and real-world adherence were linked with survival advantages. There was an estimated incremental cost of real world adherence over no adherence of $30 585 per life-year gained.137 While several reports suggest that suboptimal adherence generally and cardiovascular and hypertension medications specifically is associated with higher healthcare costs, other evidence indicates incremental cost per life-year gained.
Once poor adherence is detected, efforts should focus on implementing interventions to improve and maintain long-term adherence. This can be achieved using several different approaches, which concern not only patients but also physicians, health care systems and the medical therapy itself as already partly discussed in Suboptimal Adherence: Contributing and Associated Factors of this review and illustrated in Table 5. Despite the multiplicity of possible interventions, meta-analyses and systematic reviews on interventions to ameliorate adherence conducted between 1996 and 2014 tended to conclude that current methods of improving medication adherence for chronic health problems were mostly complex, not very effective and with a minor effect size.152–155 In addition, it was difficult to demonstrate that one approach is better than another is at increasing adherence and combination of approaches appeared to be best.