INTRODUCTION — Nonadherence to evidence-based pharmacotherapy is associated with excess morbidity and mortality [1,2]. The importance of adherence with lipid-altering medications in patients with dyslipidemia was demonstrated in a post hoc analysis of data from the West of Scotland Coronary Prevention Study (WOSCOPS) [3]. In this primary prevention study of men with hypercholesterolemia, pravastatin therapy was shown to decrease cardiovascular morbidity and mortality (figure 1).
The mean adherence for the entire group was 70 percent. Those patients in the treatment group with more than 75 percent adherence had the following benefits:
●Fewer definite coronary events (risk reduction of 38 versus 31 percent compared with patients treated with placebo)
●Lower cardiovascular mortality (risk reduction of 37 versus 32 percent)
This dose-response effect associated with better adherence argues for improving medication adherence to maximize therapeutic response. Other benefits of adherence to drug therapy may include decreased utilization of medical services, better quality of life, and reduced social costs such as lost productivity [4].
Similarly, a population-based cohort study of Swedish patients with type 2 diabetes showed that higher refill adherence to lipid-lowering medications was associated with a lower risk of cardiovascular disease in primary and secondary prevention patients. Furthermore, non-persistence (not having medications on hand for over 180 days) was associated with a mortality risk 6 percent higher in primary prevention patients and 18 percent higher in secondary prevention patients [5].
In addition, since the risk factors for coronary heart disease (eg, lipid abnormalities, smoking, sedentary lifestyle, hypertension, diabetes mellitus) tend to be additive, nonadherence to medical or behavioral treatment of any individual risk factor results in a higher level of risk [6,7]. Furthermore, nonadherence to one part of the medical regimen may increase the likelihood of nonadherence to other components.
The American Heart Association (AHA) expert panel on compliance has reviewed existing adherence-enhancing strategies found effective in clinical research and has made recommendations involving patient education, contracts, self-monitoring, tailoring interventions to individual needs, telephone follow-ups, and social support [8]. Strategies likely to be effective to address patient nonadherence to lipid-altering therapy and lifestyle change recommendations are reviewed here. A discussion of the data concerning the effectiveness of lipid-altering medication is presented separately. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)
FACTORS AFFECTING TREATMENT ADHERENCE — Numerous patient-related factors that are not specific to the type of treatment can affect adherence to treatment regimens.
Cognitive impairment — Memory or concentration problems, or loss of capacity to understand the impact of treatment versus no treatment may have a substantial impact or be relatively subtle following stroke, myocardial infarction, hypoxia, surgery, and other disorders or procedures.
Psychopathology — Clinical depression (found in 18 to 44 percent of cardiac patients over the course of their disease [9]) influences a patient's energy to make and sustain changes, increases hopelessness, and promotes thoughts that treatment does not matter. Anxiety may be associated with the negative interpretation of side effects and greater somatic sensitivity to symptoms and side effects, both of which may lead to avoidance of medical treatment and caregivers [10,11]. A high level of anger and hostility is four times as likely in heart transplant patients with persistent medication compliance problems [12].
Motivation for treatment — Feeling pressured by others and conflicted about change is associated with nonadherence; by comparison, intrinsically motivating reasons which involve positive self-related outcomes help sustain adherence (eg, "I want to stay healthy to see my grandchildren grow up") [13]. Fear tends to promote initial but not sustained adherence and also can lead to denial and fatalism [14].
Functional illiteracy — Functional health illiteracy is common in some patient groups. In one study, 41 percent of patients age 60 and older did not understand the phrase "take on an empty stomach"; 50 percent of their spouses and 25 percent of their children were unaware of the patient having this difficulty [15].
Interactions with clinicians — Improved adherence often results when clinicians use nontechnical language when communicating with patients, provide precise information about the effects of treatment and potential side effects, and collaborate on a treatment plan that incorporates the patient's values, motivations, and difficulties with treatment [16-18].
Lack of clinical follow-up — Lack of clinical follow-up may adversely affect adherence and treatment outcomes. These can be substantially improved using a case management approach in which follow-up phone calls to deal with adherence problems are made by nurses or allied health care providers. In a study of 585 patients hospitalized for an acute myocardial infarction and randomized to a case management intervention with frequent follow-up or usual medical care, the case management approach resulted in the following benefits [19]:
●Increased smoking cessation rate at two month follow-up (70 versus 50 percent, p = 0.03)
●Decreased plasma low-density lipoprotein (LDL) cholesterol levels at two months (107 versus 132 mg/dL [2.77 versus 3.41 mmol/L], p = 0.001)
●Improved functional capacity at six months (9.3 versus 8.4 metabolic equivalents [METS], p = 0.001)
Complexity and organization of regimen — Complex regimens involving many medications taken at different times are associated with poor adherence. As an example, a cohort study found that nonadherence to statins and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers increased with the complexity of the treatment regimen and prescription filling as measured by numbers of prescribed medications, prescribers, pharmacies, pharmacy visits, and pharmacy visits per prescription fill [7].
Simplified regimens or the use of charts or pill organizers can improve adherence, as can involving spouses, other family members, or home nursing [12].
Side effects of medications — Although statins are first-line, low-density lipoprotein (LDL) cholesterol-lowering medications for the primary and secondary prevention of cardiovascular disease, adverse effects are often reported by patients. For example, statin-associated muscle symptoms have a prevalence of 7 to 29 percent in registries and observational studies [20,21]. (See "Low-density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors" and "Statins: Actions, side effects, and administration" and "Low-density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors", section on 'Fibrates'.)
Cost, inconvenience, and lifestyle barriers — Financial cost is a barrier for many patients. The inconvenience of changing a daily routine to incorporate medications, or the maintenance of a medication schedule while traveling, camping, or on vacation, may affect adherence. A study found that obtaining statins through a mail-order pharmacy rather than a local pharmacy was associated with improved control of LDL cholesterol [22]. Medications also often require lifestyle changes (eg, in alcohol consumption and diet) that may be difficult to implement or maintain.
Health beliefs — Health beliefs are particularly important in medication adherence (table 1) [23,24].
●Risk perceptions concerning illness – The perceived threat of cardiovascular disease is often minimized by patients (eg, patients in their 30s or 40s who believe they are not susceptible to an "old person's" disease).
●Perceived benefits of treatment – Clear communication of progress (changes in lipid values and their meaning to the patient) is essential. The lack of perceived symptoms in lipid disorders means that the patient's understanding of the benefits of treatment and his or her motivation to continue is based upon the effectiveness of communication with the medical team.
●Barrier beliefs concerning medicines or a specific medicine – Patients often are concerned about medication interactions or taking too many medications (eg, "When I have to take so many medications, I feel old"). They also frequently have misinformation or misunderstandings about treatment (eg, "When my labs are normal, I can quit treatment"). Personal beliefs about "becoming dependent" upon medicine or preferences for lifestyle changes or alternative approaches to healthcare also frequently affect medication adherence.
SPECIFIC FACTORS AFFECTING ADHERENCE TO LIFESTYLE RECOMMENDATIONS — In addition to medication adherence concerns, other factors affect adherence to lifestyle changes. Patients often struggle with remembering and following through on lifestyle recommendations [16,25].
Stage of change — The patient's stage of change (their readiness to adopt a change in lifestyle) is a more important consideration for lifestyle recommendations than when medications are prescribed. The discussion which follows is based upon the Stages of Change Model [26].
Effective clinician intervention differs at each stage (table 2). In assessing stage of change, the question for the clinician is whether the patient is ready to adopt the recommended lifestyle change.
If not, is the patient:
●Not thinking about it at all (precontemplation stage)
●Thinking about it (contemplation stage)
●Ready to start planning (preparation stage)
If so, is the patient:
●Ready to implement it (action stage)
●Already making the change (maintenance stage)
Cost, inconvenience, and lifestyle barriers — In addition to the cost, lifestyle, and readiness issues identified above, past experience with the recommended behavior is often critical in making a lifestyle change such as stopping smoking or losing weight. Although patients often characterize past experiences as failures, these experiences may provide useful information regarding why they "failed" and give clues about what they need to do to succeed.
Health beliefs — The perceived risk of illness discussed above is relevant to both medication and lifestyle adherence, but the following health beliefs are primarily relevant to making successful lifestyle changes.
●Perceived benefits of lifestyle change – Patients may need information regarding the connection between exercise, weight reduction, or other lifestyle change and the desired medical outcome. Misinformation or ignorance is common (eg, patients often are not aware that a modest weight loss or increase in exercise can be medically beneficial, or that even infrequent smoking increases the risk of sudden cardiac death). Poor lifestyle assessment by the patient is also common (eg, patients often overestimate the amount of exercise they get on their job).
●Perceived barriers to lifestyle change – Personal barrier beliefs may be challenging (eg, "Smoking is my only pleasure") but often may be addressed indirectly (eg, by helping the patient develop other sources of pleasure). Cultural barrier beliefs about lifestyle changes may also need to be discussed (eg, "If you're too thin, you're not healthy"), as will peer group beliefs and pressures.
●Self-efficacy beliefs – Based upon past experience, patients often believe they are not capable of making recommended lifestyle changes. This is highly predictive of the initial effort in making change [25]. Low self-efficacy can be changed over time with education and positive experiences of success.
Social support — Social support for making lifestyle change is particularly important. Absence of support can add to the patient's sense that having an illness or treating it doesn't matter, and this may exacerbate depression. Attitudes of spouse, family and friends can support or undermine motivation for medication treatment or lifestyle change. Their specific behaviors can directly affect the ability to adhere to a treatment plan (eg, quitting smoking when a spouse smokes; changing to a low-fat diet when family traditions involve high-fat foods).
STRATEGIES FOR INCREASING ADHERENCE — Clinicians can incorporate knowledge of the above factors into regular patient visits without adding significantly to the amount of time spent with patients.
Reduce the likelihood of nonadherence in advance — The patient's difficulties in initiating change need to be addressed at the time recommendations for medications or lifestyle changes are made.
The following initial measures may therefore improve patient adherence and outcome:
●Provide a rationale for the treatment in the patient's language – Health care providers should identify and support the patient's positive, personal reasons for treatment and lifestyle changes; address misperceptions of illness risk; and reinforce the positive medical benefits of treatment.
●Use motivational interviewing strategies where possible – Perhaps the most difficult task of a clinical encounter that includes a discussion of adherence is conducting it in such a way as to allow the patient to maintain a high level of personal motivation for adherence to treatment after the encounter. Motivational interviewing strategies such as eliciting the patient's perspective on taking medication and making lifestyle changes, expressing acceptance and support for the patient's difficulties and successes, affirming the patient's freedom to choose the best course of action, and accurately identifying and responding to the patient's stage of change have research-based evidence of success in accomplishing this [27,28].
●Identify and address general barriers to adherence – Formal assessment of general barriers does not need to be conducted with every patient. However, the caregiver should assess suspected cognitive impairment with a mental status examination and suspected psychopathology with questions relating to mood, coping, sleep, and appetite disturbance. Caregivers should always assess motivation for treatment by asking patients why they want to undergo treatment and encouraging them to have personal as well as medical reasons for treatment. Assessment for functional illiteracy can be accomplished by asking patients to repeat and explain treatment instructions.
●Collaborate on the treatment plan – The patient's health beliefs and concerns should be incorporated into the treatment plan.
●Identify and address specific barriers to implementation – The caregiver should assess the patient's stage of change and develop an appropriate stage intervention (table 2); address cost and functional barriers to treatment and barrier beliefs regarding medications or lifestyle changes; and confirm agreement and patient understanding by asking the patient to describe schedule and specific directions for taking medications, or define the lifestyle treatment goal and the method for achieving it.
●Encourage the patient to obtain social support for treatment – In making lifestyle changes, family and friends can help with encouragement and motivation during the action stage and with stimulus control and reinforcement during the maintenance stage (table 3). Support groups of others making similar changes (eg, WomenHeart, Mended Hearts) are helpful in reinforcing positive health motivations and behaviors and in providing good role models.
●Frequent follow-up – Phone calls or messages via the electronic patient portal from nurses or other clinic staff can improve adherence substantially by answering patient questions, monitoring and addressing patient-initiated cessation of treatment, and reinforcing motivation for continuing engagement in medical treatment or lifestyle change.
●A 2016 Cochrane Review recommends intensive team-based interventions to improve patient adherence to lipid-lowering medications [29].
Identify and address nonadherence — In follow-up visits, patient adherence needs to be assessed and nonadherence dealt with using the following principles:
●Assess adherence during each appointment by two simple questions – "In the past two weeks, what percent of your cholesterol medicine have you taken?" (If less than 100 percent, "What is the main reason you might miss your medication?")
●Ask about medication side effects or problems associated with nonadherence to lifestyle change.
●Identify nonadherence and distinguish it from ineffectiveness of treatment – The caregiver should maintain an open, nonjudgmental attitude to encourage truthful discussion about adherence and should assess patient understanding of treatment protocol by asking the patient to describe treatment plan in detail [28]. Patient adherence should be assessed using multiple information sources (treatment outcome, patient report, spouse report, etc), and additional evidence should be obtained as needed (eg, note if prescriptions are being renewed at appropriate times and, when feasible, have patients bring pill bottles to every doctor visit to examine use). Finally, the clinician should decide whether the percentage of likely nonadherence accounts for treatment ineffectiveness.
●Address nonadherence from the patient's perspective – Both general and specific factors influencing adherence should be identified for discussion. Also, discuss nonadherence in the context of the patient's values, but let the patient come to a decision about what should be done (eg, "You said you wanted to be around to see your grandchildren grow up, but you are not taking your medication. What do you make of that?").
●Get help from other clinic staff in monitoring the patient, following up, and reinforcing positive aspects of adherence.
Deal with continuing nonadherence — Continuing nonadherence can be frustrating for the clinician as well as the patient and can affect their short- and long-term relationship. Although caregivers should actively support adherence, they should also encourage an ongoing discussion about adherence issues from the nonadherent patient's perspective. While acknowledging patient concerns, caregivers can help patients notice symptom remission and improved laboratory results associated with treatment and lifestyle change and can encourage them to find social support or assistance for adherence.
In addition, health care providers should decide how continuing nonadherence will affect their relationship with the patient. If necessary, clinicians should give patient conditions to meet if they expect to continue treatment. However, offering understanding and being willing to work with a nonadherent patient may improve future adherence or adherence with other caregivers. Clinicians should also remain patient since progress may be slow and meaningful change often takes time.
OTHER STRATEGIES — Financial incentives can improve lipid reduction, in part through improved adherence. A randomized trial conducted in primary care practices in the United States found that financial incentives to patients improved medication adherence, and combined financial incentives to patients and providers led to small additional reductions in low-density lipoprotein (LDL) cholesterol compared with a control group (-33.6 mg/dL versus -25.1 mg/dL [-0.87 mmol/L versus -0.65 mmol/L]) [30].
RECOMMENDATIONS OF OTHERS — The American College of Cardiology/American Heart Association (ACC/AHA) recommends performing a fasting lipid profile 4 to 12 weeks after initiating statin therapy so as to assess adherence [31]. A high-intensity statin regimen should reduce low-density lipoprotein (LDL) cholesterol by at least 50 percent from baseline, while a moderate-intensity statin regimen should reduce LDL cholesterol by 30 to 50 percent.
Patients who do not demonstrate this reduction in LDL cholesterol and who are tolerating statin therapy should have the importance of adherence to medications and lifestyle changes reinforced and secondary causes of hypercholesterolemia excluded. Repeat lipid testing should be performed in 4 to 12 weeks. If LDL cholesterol levels do not fall as anticipated, adherence should again be reinforced and consideration given to increasing statin intensity or adding nonstatin lipid-lowering medications.
Patients who demonstrate an appropriate reduction in LDL cholesterol should also have the importance of adherence reinforced and have repeat lipid testing performed every 3 to 12 months.
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 5th to 6th 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 10th to 12th 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 e-mail 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
●Adherence to lipid-altering medications and lifestyle changes is associated with better clinical outcomes. (See 'Introduction' above.)
●Patient factors that can affect adhering to treatments include cognitive impairment, psychopathology, the patient's motivation for treatment, and the patient's health literacy. Other general factors affecting adherence include patient-clinician interactions and how follow-up is arranged. (See 'Factors affecting treatment adherence' above.)
●Factors specific to medication adherence include medication side effects, the complexity of the medication regimen, the burdens of medication adherence (eg, cost, inconvenience, and required changes in lifestyle), and patient beliefs about medication therapy. (See 'Factors affecting treatment adherence' above.)
●Factors specific to lifestyle adherence include the patient's readiness to make changes, the burdens of lifestyle changes, patient beliefs about lifestyle changes, and the availability of social support for lifestyle changes. (See 'Specific factors affecting adherence to lifestyle recommendations' above.)
●Clinicians can work to increase the likelihood of adherence preemptively by explaining the rationale for treatment in language the patient can understand, using motivational interviewing techniques, identifying and addressing potential barriers to adherence, and collaborating on the plan of treatment. (See 'Reduce the likelihood of nonadherence in advance' above.)
●Clinicians should identify nonadherence and its causes by asking nonjudgmental questions about adherence and by asking about medication side effects and the burdens of lifestyle changes. Clinicians should try to address issues by working from the patient's perspective. An excellent clinician-patient relationship is key. The clinician must work toward establishing a collaborative process for problem solving. (See 'Identify and address nonadherence' above.)
