Mind the Gap: Medication Adherence Divide Between Trials and the Real-World

By Devika Aggarwal, MD, Nishaki Mehta, MD

All of us have witnessed an adverse patient outcome due to a medication error- gastrointestinal bleeding from taking too much aspirin, acute stent thrombosis after stopping clopidogrel a month after coronary stent placement, or acute renal failure from taking the wrong dose of lasix. Often, we negotiate with patients about taking a medication in lieu of another one. We have also had patients rationing their medications or decide to selectively take the medications they regard as ‘most important’.

With the release of trials, new drugs are inevitably added to the armament of treatment regimens and eventually to patients’ pillboxes. Over the past few decades, the average number of pills a patient takes has increased steadily.1 Polypharmacy, the concomitant use of five or more drugs, is a commonly encountered problem in patients with cardiovascular diseases, who take a median of seven pills daily, with some patients taking up to 27 pills daily.2,3 A high pill burden is associated with medication nonadherence and hence poor outcomes. This is due in part to lower knowledge and understanding of the medications with increasing number of prescribed medications.4–6 Hence, the observed benefit noted in the trials may not translate into clinical practice for patients. Moreover, adverse consequences of medication nonadherence (consciously or inadvertently missing medications, taking the wrong dosage, incorrect frequency or timing) contribute heavily to health services utilization and costs.7,8 Older adults are an especially vulnerable population as they have a higher prevalence of polypharmacy, inadequate health literacy, nonadherence, and hence poor outcomes.

The field of HIV medicine has made the largest effort towards bridging this gap since adherence to antiretrovirals is crucial to prevent virologic failure and the development of resistance. However, this issue is common to all areas of medicine but is not accorded a high priority.  There has been some research into potential interventions to address this gap. Here we briefly discuss some of the potential interventions, ranging from simple to high-tech.


Deprescribing is a practice aimed at decreasing the medication burden and reducing the risk of medication-associated adverse events. It requires time, attention to detail, and effective communication and is not considered a priority in a system that rewards starting new medications. 9 Cardiovascular medications are commonly prescribed without an end date, although there is little evidence regarding efficacy and safety in the long run. 10 Classes such as lipid-lowering medications should be considered as potential targets for deprescribing during follow-up visits, as patients’ condition and the goals of treatment evolve. Shared decision making can help to align medications with patient goals at every visit.

Pharmacy-based Interventions

Pharmacy-based interventions are the most commonly proposed solutions for polypharmacy. These include incorporating clinical pharmacists into the patients’ care team in hospitals, clinics, and nursing homes. Pharmacists can review the list of medications and help physicians identify inappropriate or incorrect medications. This can be especially beneficial during the discharge process where medication reconciliation errors are common. Pharmacists can assist by conducting patient interviews and counselling. Although the data regarding pharmaceutical care in improving hard endpoints are conflicting, the impact in reducing the number of medications, drug interactions, and healthcare costs has been demonstrated.13–15

Visual Aids

Visual memory plays an important role in day-to-day activities, including medication administration. HIV clinics use standardized pill charts in examination rooms as a tool to gauge adherence. A similar intervention in cardiology practice could be the use of personalized visual pill charts to marry the language used by patients (pill color and shape) with the language used by healthcare teams (drug name and dosage). In prior small studies, visual pill charts have shown potential to help patients keep track of the medications and translate the medication regimen into a visual prompt that reminds the patient what needs to be taken when and how often.16,17

Technology-guided Interventions

As technology penetrates into all aspects of modern-day life, innovative solutions have been proposed for medication nonadherence. Smartphone applications are being developed that allow patients to upload customized medication regimens and reward patients for adherence through gamified interactions.18 Other tools such as smart pill bottles can provide reminders for the patients to take their medication and record data regarding adherence. Though more data is needed, technology-driven innovations may prove to be effective, low-cost interventions leading to behavioural changes promoting medication adherence.

A major limitation is that all the tools mentioned above have only been evaluated in small studies and are not implemented in routine practice. Large-scale studies with stakeholder input may motivate change in this critical area. Empowering our patients to adhere to their prescriptions is critical for applying the ‘trial outcomes benefits” to the real world.


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  17. Kripalani S, Schmotzer B, Jacobson TA. Improving Medication Adherence through Graphically Enhanced Interventions in Coronary Heart Disease (IMAGE-CHD): a randomized controlled trial. J Gen Intern Med. 2012;27(12):1609-1617. doi:10.1007/s11606-012-2136-z
  18. Li A, Del Olmo MG, Fong M, et al. Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial. BMJ Open. 2021;11(8):e047041. doi:10.1136/bmjopen-2020-047041