Medication Adherence: The Missing Link In Cholesterol Care

Adherence in cholesterol therapy is taking medication for lowering lipids on time (on the right days and the right dose) for the right period of time. Adherence is a critical component of achieving intended health benefits such as heart attack and stroke prevention. As risk stratification methods and treatment options improve, and as a new and innovative pipeline emerges, adherence to prescribed lipid lowering therapies remains a key determinant of success between healthcare provider intention and desired health outcomes.

Why It Matters

Management of cholesterol levels is a long term investment – the majority of the rewards are gained gradually over time. In order to achieve these rewards, the right amount and type of lipid lowering medication needs to be prescribed and taken regularly and on time. The body doesn’t store yesterday’s tablets for next month – it is essential to realise the true potential of the powerful agents we have at our disposal for the risk reduction of major cardiovascular events, and that is by giving them to patients on time and every time. In addition to statins, consideration should also be given to adding ezetimibe or PCSK9 inhibitors to the patient’s treatment regimen.

1) The prescription is not the outcome

The gap between what doctors prescribe and what patients actually take can explain many so-called “treatment failures.” Are missed doses or delayed refills masquerading as ineffective medications? Unresolved side effects, even ones that patients attribute to the medication but never report to their doctor, can greatly decrease adherence to a powerful regimen. However, rather than investing time and money in a more intense regimen to address non-response, the doctor may be wasting both cost and patient misery by simply implementing the initial treatment plan more effectively.

The frame for the problem to be solved shifts for healthcare providers from “what medication should I prescribe?” to “what medication will this person be able to take for years to come?” and considers the factors that can be changed through good teamwork to address the patient level barriers to adherence that may interfere with successful medication taking.

2) Unacceptably low levels of adherence could lead to avoidable rates of heart and vascular disease

Missing doses of lipid lowering medication can lead to serious health problems for patients such as heart attacks and strokes, as well as unnecessary hospital admissions. The high risk to their health as a result of high cholesterol levels may not be apparent until something serious happens. Because of this patients on lipid lowering therapy often find it difficult to remember to take their pills on time. Patients with symptom visible symptoms of their condition, such as pain, find it easier to remember to take their medication as prescribed.

The risk of “no dosing” goes beyond complete discontinuation of lipid therapy to include episodes of intermittent or inconsistent dosing that produce large swings in the patient’s LDL levels. While a patient might take all of his or her lipid medication on the right days for several months, he or she is just as likely to miss several doses here and there and then go back on treatment. Thus, fluctuations in lipid levels can be misinterpreted as resistance to effective therapy.

3) To what extent do patients comply with treatment? And what implications does this have for the health system’s workload and costs, and for a number of quality indicators?

Nonadherence to cholesterol therapy leads to increased healthcare utilization such as repeat office visits, repeated laboratory tests, use of the emergency department, and invasive interventional procedures requiring additional follow ups on both primary care physicians and cardiologists. However, the reason for uncontrolled therapy is often related to issues of access and tolerability, resulting in increasing health care costs without corresponding increases in health outcomes.

The refill gaps also could make it more difficult to measure performance and to implement reimbursement schemes that pay for performance, such as targeting patients’ LDL levels. “Many quality measures are designed to measure the continuity of therapy throughout the year,” said Mr. Kowalcyk. “As a result, practices experiencing frequent refill gaps may not be performing as well as they would if they were initially prescribed the right amount and type of therapy.”

4) Adherence to medication is a health equity issue. Patients from minority or less affluent backgrounds are more likely to have suboptimal treatment outcomes

Medication adherence—completing a course of treatment as prescribed—is affected by many of the same factors that affect the rest of us on a daily basis. Factors like cost, transportation, language, health literacy, work, caregiver responsibilities, and pharmacy location affect a patient’s ability to complete his or her treatment. For example, financially stressed patients might skip or divide doses of costly or expensive to obtain medication in order to have money for other bills. Others might understand the treatment plan, but be unable to get to follow up appointments or the pharmacy for needed prescription refills. Patients and their families who speak little or no English may experience confusion about taking the correct dose or side effects when they interact with healthcare providers. Even long-term treatment for chronic conditions can be misinterpreted by patients who do not fully understand the benefits and consequences of taking a particular medication.

unless health adherence support is built- in to routine cardiovascular health care, health disparities will persist regardless of new treatment and biomarkers. First we need to translate the new medications and risk factors into practice for those most at risk.

5) Potential 5th risk: Misuse, Side Effects, Misinformation which can interfere with long-term use.

Side effects, long term effects, and misinformation from other sources can cause many patients to stop taking prescribed cholesterol medications. Although patients taking these medications report muscle pain or other symptoms, the evidence does not support any link to the medication. Patients are also concerned about the potential for liver damage, memory loss, and becoming dependent on the medication. These concerns are exacerbated if no one monitors for side effects after the patient picks up the prescription.

Patients want a treatment plan that fits within their preferences and tolerance. That means they want a say in their care. Shared decision making is not a “soft skill”, but it is a powerful clinical tool that can help patients stay on their planned course of treatment.

Who It Affects

The impact will be greatest for patients with very high levels of LDL (bad) cholesterol or with established cardiovascular disease on long term therapy for prevention of cardiovascular events. This will include patients with very high LDL cholesterol levels as well as patients with established cardiovascular disease, such as prior heart attack/stroke, diabetes, chronic kidney disease and patients with familial hypercholesterolemia who generally require initiation of therapy at earlier time points on higher doses of statin.

1) Patients with a high risk of disease progression for whom adherence to treatment is paramount

Patients in secondary prevention (those with established atherosclerotic cardiovascular disease) get large benefits from reliable long-term lipid lowering therapy. Their baseline risk is high, and the potential consequences of missing a dose of their lipid-lowering medication are avoidable lesions, events etc. Therefore adherence support should be part of standard and essential care, not an add on.

Patients with very high levels of LDL cholesterol, such as those with familial hypercholesterolemia (FH) and their families, are often subjected to misinformed health messages over a period of decades. Patients and the parents of children with very high LDL cholesterol levels are often put on pharmacological therapy for several decades, and hence, it is not adequate to develop only strategies to counsel patients in a single session. Instead, long-term adherence and engagement in treatment plans need to be promoted. Hence, persistence in correcting patients’ misconceptions over a long period of time is more important than immediate success.

2) Patients in primary prevention who may not feel urgency, therefore it is recommended that all patients receive individualized explanations regarding the purpose of the screening colonography and to discuss with them in advance the possibility that they will experience some discomfort during the procedure.

A particularly challenging problem for those for whom preventive therapy is indicated for a first event, is patient motivation. The majority of the population with high cholesterol has no symptoms and is unaware that they are affected by this condition. Most patients feel well and do not understand the necessity of taking a life-long daily pill for a condition which does not manifest itself in any symptoms. Compliance is enhanced when the patient is fully informed how the daily therapy can save him/her energy to continue to work, to live a active lifestyle and to take good care for his/her family.

Most medications have complicated dosing regimens and sometimes even unwanted side effects. But for patients with several medical conditions, the biggest challenge of all can be remembering to take all of their medications at the right time. Simplifying the dosing interval and association with common routines, such as meals, can help patients manage their “piles of pills.”

3) Clinicians, pharmacists, and care teams

Managing adherence to cholesterol treatment is not the sole responsibility of one health care profession. Rather, it should be managed by a group of health care professionals who work together to ensure that patients are taking the appropriate amount and type of cholesterol therapy medication at the appropriate time. Pharmacists can play a vital role in managing the patient on cholesterol therapy by identifying “refill gaps” in a patient’s current medication regimen as well as communicating with patients regarding their perceived effects and actual effects of cholesterol medications. The pharmacist can also prescribe or recommend various tools that can aid in adherence to recommended cholesterol therapy.

While there are many nonmedical factors that clinics cannot address, care coordinators and community health workers can make a difference. They can transport patients to and from clinics, schedule follow-up appointments, translate for patients who do not speak English, and connect patients and families with family members, friends, and community-based resources that can support patients and their families in managing illness and adherence to medication regimens.

4) Health systems and payers

The payer can strongly influence adherence of the treated patient through formulary placement, copay levels, prior authorization requirements and refill limits. Delays in processing approvals and high out of pocket costs are a recurring problem in many offices and can prevent the use of newer and more expensive agents. Uncontrolled cholesterol can lead to costly hospitalizations and readmissions as well as serious long-term health consequences for health system patients.

For prescription medications, PBMs and Insurers can either add friction to the system or mitigate it. Introducing friction into the system by the PBM/Insurer can negatively impact a patient’s likelihood to remain on therapy, especially for long term medications with established efficacy and safety profiles. Simplifying approvals, publishing stable copays, and increasing the day supply can all help to reduce friction and improve adherence.

5) Families, caregivers, and community organizations

Family members and caregivers can be used as adherence tools in supporting adherence both prior to and after individuals have received education and counseling from healthcare providers. In addition to clinic-based adherence tools and strategies, community-based programs and services such as those offered through community-based organizations, faith-based organizations, retirement communities, senior centers, and youth groups can provide health education and health promotion messages; screening and testing for various diseases and conditions; and facilitate navigation of the health care system for individuals and their families. For older adults, support from family members and caregivers such as remembering to take medication; supporting the individual in refilling medication; and accompanying the individual to clinic visits can be helpful.

What Changes

• Improving adherence requires routine measurement, empathetic conversation, and system level supports that make the right choice the easy choice. Below are practical changes that align with day to day clinical work and population health goals. 1) Make adherence assessment a standard vital sign Adherence should be checked at every encounter in a nonjudgmental way, using simple questions that normalize difficulty. Helpful examples include: “Many people miss doses sometimes. In the past two weeks, how many doses do you think you missed?” and “What gets in the way of taking this medicine every day?” This approach reduces shame and increases honesty. Link adherence questions to problem solving, not punishment. When a patient admits missed doses, the next step should be support: simplifying regimens, addressing cost, managing side effects, and setting up reminders. Practical tip for clinics Use refill history as a starting point, then confirm with the patient. Pharmacy refill measures such as proportion of days covered can flag gaps, but they do not explain why gaps occur. A quick discussion can uncover issues like pharmacy hours, travel, forgetfulness, or fear of side effects. 2) Treat side effects early and preserve trust Side effects are a leading reason people stop therapy, so early follow up matters. Many patients discontinue within the first months if symptoms appear and no one checks in. A planned follow up call or message after initiation can catch problems before the patient gives up. Clinicians can often maintain lipid lowering benefits by adjusting the plan rather than abandoning therapy. Options may include switching to a different statin, using a lower dose with gradual titration, trying alternate day dosing when appropriate, or adding a nonstatin agent to reach LDL goals with better tolerance. The key is to communicate that there are multiple paths to success and that stopping without discussion is risky. 3) Simplify regimens and reduce daily burden The fewer steps a patient must remember, the higher the chance therapy will be taken consistently. Once daily dosing is generally easier than multiple daily dosing. Aligning medication time with an existing habit such as brushing teeth, breakfast, or bedtime improves routine formation. Consider combination therapy when it reduces pill burden and improves consistency. For patients who need more than one lipid lowering agent, combination pills or coordinated refill schedules can reduce complexity. Practical tools that often help Low cost aids such as pill boxes, calendar packs, blister packaging, and labeled dosing schedules can improve day to day reliability. For some patients, a weekly pill organizer is enough. For others, pharmacy prepared packaging or family support is more effective. 4) Build team based workflows that support persistence Pharmacist led lipid management and nurse follow up can improve adherence while reducing physician workload. In many settings, pharmacists can provide medication counseling, refill coordination, side effect troubleshooting, and dose titration under protocols. Nurses and care managers can run check ins, reinforce education, and monitor labs. Create clear roles so adherence work does not fall through the cracks. For example: The prescriber starts therapy and sets LDL goals. The pharmacist checks refill patterns and provides counseling. Nursing staff contacts patients after initiation and after dose changes. Care coordinators address cost, transportation, and appointment barriers. 5) Optimize access and affordability Cost related nonadherence is common and often treatable. Many patients are reluctant to tell their healthcare providers that they are unable to afford to take their medications as prescribed. By asking the question, “Are you ever a doing a cheaper version of this medication or skipping a dose or a medication because of cost?” the physician can learn that affordable alternatives are available such as generics, therapeutic alternatives, patient assistance programs, larger day supply, mail order, and formulary friendly alternatives. Reduce administrative tasks for patients with High Risk Medical Conditions. Prior authorization can often cause significant treatment delays for these patients. Improve your company’s internal processes to make decisions earlier. Obtain early benefit determination with accurate documentation. 6) Use technology thoughtfully without widening disparities While digital tools like patient portals, telehealth, and automated reminders can help patients take their medication on time by sending reminders and other alerts, these tools only work as well as the patient’s smartphone, data plan, and experience with apps. Technology is most effective when paired with human support and when patients have alternative options for those who do not want to communicate by phone or in person. Our refill monitoring service identifies timely opportunities for the pharmacist or physician to contact patients to prevent a recurrence of elevated cholesterol by identifying the reason for the refill gap and resolving the reason for nonadherence prior to the next dose being due. 7) Measure adherence, then intervene quickly Instead of leaving adherence improvement to chance, Measurement makes it a target. Most programs aim to reach “covered days” over a span of time, and typically strive to hit nearly every day of the year. If coverage drops below a certain level, outreach should not be discretionary. • Programs that are high quality and effective connect data and action to improve results for children and families. Examples of effective approaches include • Early childhood programs designed to support the learning and social skills of young children with disabilities; • Family support programs which offer concrete support, education, advocacy and care coordination to parents and their children with disabilities and special health care Automated lists of patients with refill gaps Pharmacist counseling calls for gaps and side effects Same day prescription renewal workflows Education that focuses on personal risk and benefits Follow up labs paired with adherence review 8) Reframe escalation decisions: check adherence first Keep LDL levels that are above goal out of sight. Consider the cost to patient when goal LDL levels are in plain sight. Keep in mind that many expensive treatments and pejorative labels (such as “nonresponder”) are often given before doctor knows if patient is even taking all of their prescribed medication. Only after you have identified and addressed all patient level and system level barriers to adherence should you consider further escalation of therapy. Simplify the patient’s medication list as well. Rather than distributing limited resources thinly and evenly across the entire continuum of care, these strategies ensure that pharmaceuticals are used to maximum value at key points in time. Clinically and financially, this offers the best combination of effectiveness and cost. It avoids unnecessary changes to treatment for the patient, while enhancing the value of pharmaceuticals for the health system as a whole. 9) Use newly identified risk markers (Lp(a)) to motivate and to develop measures. Lp(a) is a unique, genetically determined risk factor. Discussing the patient’s level of Lp(a) can enhance the risk discussion and motivate the patient to continue on life-long therapy. The patient can gain insight into how their elevated Lp(a) contributes to their risk of CVD and learn how it impacts their individualized treatment goals. Knowing their Lp(a) level can motivate patients with elevated levels to be more diligent in controlling other factors that put them at risk for CVD and maintaining optimal levels of LDL. Patients should understand that their high Lp(a) was inherited and could not have been prevented. Their focus should be on being more vigilant with the other factors that put them at risk for CVD. We try to use your Lp(a) level for good and NOT for stress. The best use of your Lp(a) number is to empower you to take control of your health by eating healthy, lowering your LDL, lowering your blood pressure, quitting smoking, and controlling your diabetes. It should be a tool for you and your healthcare provider to follow your health course. 10) Make taking medication a part of your culture. This is a cultural revolution. The prescription is the beginning, not the end of good care. Include in your routine practice the education of patients and families, early follow up, the side effect issues, affordability assistance, tracking of refills, and long term behavioral coaching to ensure that medication is taken as prescribed. References: https://pmc.ncbi.nlm.nih.gov/articles/PMC3191684/