Cardiovascular diseases (CVDs) is a leading cause of death globally, accounting for approximately one-third of all deaths worldwide. Preventive therapy including combination therapy with aspirin, blood pressure, serum cholesterol-lowering, or diabetes medications is effective in reducing risk by as much as an estimated 80% when adherence to treatment is very high. However, among adults with CVD risk factors such as diabetes or hypertension, between 30% and 50% of medications are not taken as prescribed.1
Adherence is defined by the World Health Organization as the extent to which a person's behavior—taking medication, following a diet, and/or executing lifestyle changes—corresponds with agreed upon recommendations from a healthcare provider.2 Poor adherence decreases the effectiveness of evidence-based prevention therapies and is associated with increased morbidity and mortality.3 In addition, poor medication adherence represents a significant source of wasteful healthcare spending. An estimated $100 billion is spent annually on US healthcare services that are directly related to poor medication adherence.3 Poor adherence is pervasive and must be addressed by all members of the cardiovascular prevention team, across the care continuum.
The causes of poor adherence are myriad and complex with contributing factors at the patient, provider, and health system levels. Patient barriers to adherence include multiple comorbid conditions requiring complex medication regimens, convenience factors (eg, dosing frequency), health beliefs, behavioral factors and issues with treatment of asymptomatic diseases (eg, treatment side effects), resource constraints and high out-of-pocket costs, suboptimal health literacy, and lack of involvement in the treatment decision-making process. Provider barriers include prescription of complex drug regimens, communication barriers, ineffective communication of information about adverse effects, and poor care coordination. Health system barriers include office visit time limitations; limited access to care, prescription refills, or pharmacies; lack of team-based approaches; and inadequate health information technology. Because barriers to medication adherence are complex, solutions to improve adherence may be introduced at patient, provider, and/or healthcare system levels.4–6
Assessing Medication Adherence
Assessment of medication adherence can be direct (ie, directly observed therapy, measurement of serum levels) or indirect (ie, pill count, measurement scales, pharmacy records). Measurement scales commonly used in research and practice to assess self-reported medication adherence include the Morisky Medication Adherence Scale,7 Hill-Bone Compliance to High Blood Pressure Therapy Scale,8 the Brief Medication Questionnaire,9 and the Krousel-Wood Medication Adherence Scale-4.10 Although these assessment instruments have relatively high internal validity, they may overestimate adherence because of their reliance on self-report.
Electronic monitoring systems objectively assess medication adherence. An example is the Medication Event Monitoring System (Aardex, CH); microelectronics embedded in pill caps record the date and time when containers were opened and closed. Similar to the Medication Event Monitoring System is the Intelligent Drug Administration System, which records the date and hour that a drug was removed from blister packs.11 Major limitations include the inability of these systems to measure actual pill consumption and the limited practicality of their use in low-resource settings.
Two measures of adherence using prescription-claims data are the proportion of days covered (PDC) and medication possession ratio. The PDC is endorsed by the Pharmacy Quality Alliance as a high-quality measure of medication adherence, and the threshold of greater than 80% produces the most clinical benefit for a given medication.12 The PDC is the ratio of the number of days the patient is covered by the medication divided by the number of days the patient is eligible to have the medication on hand. The medication possession ratio is calculated as the ratio of the number of days for which a patient has medication on hand divided by the total number of days in the observed period.
Interventions and Toolkits to Improve Medication Adherence
No single strategy has proven to be the panacea for improving medication adherence. Rather, a combination of interventions that address patient-, provider-, and system-level barriers is more likely to be effective. Interventions that have been demonstrated to improve medication adherence in CVD prevention are listed in Table 1, with a summary of recent evidence supporting these interventions provided hereinafter.
Tailored Patient Education
It is essential to educate patients about the importance of adhering to prescribed medications. An informed patient is better able to collaborate to establish shared goals of therapy and a plan of care. Compared with education delivered in a single session, educational interventions that incorporate follow-up sessions are generally more effective and lead to sustained behavior change.14 In Nieuwkerk et al's15 nurse-led clinical trial of 201 patients who were newly prescribed statins, an educational intervention that consisted of a “personalized risk factor passport” and was tailored to the patient's risk for CVD resulted in significant improvement in statin adherence and reduction in patient anxiety. Other interventions that have used telephone counseling delivered by nurses or trained educators have demonstrated success in reducing hemoglobin A1c levels16 and increased refill adherence.17 Meducation, an innovative health literacy tool that includes a medication calendar and customized education written at a sixth-grade reading level, improved self-reported medication adherence, although the effect was small in this pilot study.18 The authors of these studies suggest that healthcare providers who delivered tailored education on CVD risk reduction and reinforce education at an appropriate literacy level are more likely to be successful in improving cardiovascular outcomes.
Fixed-Dose Combination Therapy
Fixed-dose combination therapy, also known as single pill combinations, has recently been recognized as a best practice to improve hypertension control globally. The World Health Organization added fixed-dose combination antihypertensive medications to the World Health Organization Essential Medicines List in July 2019.19 A systematic review of dual combination vs monotherapy as initial therapy, including 33 trials with more than 10 000 participants, showed a 27% increase in the rate of achieving blood pressure control among patients receiving dual combination therapy.20 Providers should consider prescribing combination therapy where appropriate to reduce patient burden and improve control of cardiovascular conditions.
Mobile Health Applications
Mobile phones provide a patient-centered strategy for addressing medication adherence because of the ubiquitous nature of smartphones and the ability to send alerts to take medications, track doses, and provide appropriate medication instructions. A recent systematic review21 of mobile health (mhealth) applications targeting medication adherence identified 704 applications with different features. Of those, 20 applications were identified through a quality assessment focused on behavioral strategies to enhance medication adherence through alerts, reminders, and logs; these were available in English, German, Spanish, French, Japanese, Russian, and Traditional Chinese. The MediSAFE-BP trial evaluated the impact of the Medisafe mhealth application on medication adherence and blood pressure control. The study authors found a slight increase in medication adherence in the intervention group after 12 weeks (between-group difference, 0.4 points in the Morisky Medication Adherence Scale; P = .01), but there was no corresponding improvement in blood pressure control.22 Although mobile apps offer promise, the evidence of meaningful impact on adherence and CVD risk factor management is limited, and mhealth applications have the downsides of consumer costs and limited trial periods.
Automatic Home Medication Dispenser
To address the technology gap for medication reminders especially for older adults, products such as the automatic home medication dispenser (AHMD) integrated with a smartphone application have been developed. The AHMD differs from other in-home medication dispensers because it can hold up to 90 day's supply of several medications and includes the following components to address cognitive impairment and age-related changes: counter, clock, dispensing mechanism, power source, input/output interface, locking system, transceiver and antenna, and physical indicator for alarms. Other functionalities include notifying the user of due dosage per set dosage time or due refills through audio/visual reminders and notifying the caregiver of missing dosages through calls or text messages. In a recent study,23 use of an AHMD (MedaCube) significantly increased adherence from 49% at baseline to 97% after 6 months. Although AHMD is an emergent strategy to improve medication adherence, the cost of these devices may be prohibitive in lower-income populations and low-resource settings.
Incentive-based medication adherence interventions have been demonstrated to be promising in several studies. Incentives such as a significant reduction in copayment have been associated with improved medication adherence.24 However, the reduced copayment incentives may not be applicable in some low- and middle-income countries where the health systems are not insurance based. Other incentive-based interventions have been in the form of cash, vouchers, gift cards, meals and food packages, clothing, and travel reimbursements for compliance to clinic visits and medication refills, although effectiveness has been inconsistent.25 A recent scoping review26 concluded that financial incentives were the most common behavioral economic intervention and the provision of physician-patient financial incentives was more effective in improving medication adherence than the provision of financial incentives to either physicians or patients alone.
Table 2 displays 4 medication adherence toolkits designed to support health professionals and educators. These toolkits offer best practices and resources for (1) assessing medication adherence, (2) improving medication adherence through the use of aids, (3) empowering patients to improve medication adherence, and (4) resolving barriers to medication adherence.
Medication adherence can be assessed and improved within the context of CVD prevention in the clinic, community, and home. However, improving medication adherence requires coordination and building on evidence-based strategies in practice and policy actions in both the public and private sectors. Using care coordination strategies, patient engagement and medication management tools can significantly improve medication adherence. Improving medication adherence also requires investments in health information technology and financial incentives for patients and providers. Innovations in drug delivery systems that offer a more holistic approach to managing adherence to drug therapy may help to alleviate the burden on patients.
1. Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med
. 2012;125(9):882–887.e1. doi:.
2. World Health Organization (WHO). Chapter XIII: hypertension in adherence to long term therapies-evidence for action. 2003. http://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf?sequence=1
. Updated 2003. Accessed May 19, 2018.
3. Iuga AO, McGuire MJ. Adherence and health care costs. Risk Manag Healthc Policy
. 2014;7:35–44. doi:.
4. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc
. 2011;86(4):304–314. doi:.
5. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev
. 2014;11:CD000011. doi:.
6. Viswanathan M, Golin CE, Jones CD, et al. Closing the quality gap: revisiting the state of the science (vol. 4: medication adherence interventions: comparative effectiveness). Evid Rep Technol Assess (Full Rep)
7. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich)
8. Kim MT, Hill MN, Bone LR, Levine DM. Development and testing of the Hill-Bone compliance to high blood pressure therapy scale. Prog Cardiovasc Nurs
9. Svarstad BL, Chewning BA, Sleath BL, Claesson C. The brief medication questionnaire: a tool for screening patient adherence and barriers to adherence. Patient Educ Couns
. 1999;37(2):113–124. doi:S0738-3991(98)00107-4.
10. Krousel-Wood M, Joyce C, Holt EW, et al. Development and evaluation of a self-report tool to predict low pharmacy refill adherence in elderly patients with uncontrolled hypertension. Pharmacotherapy
. 2013;33(8):798–811. doi:.
11. Park LG, Howie-Esquivel J, Dracup K. Electronic measurement of medication adherence. West J Nurs Res
. 2015;37(1):28–49. doi:.
12. Pharmacy Quality Alliance. PQA adherence measures. https://www.pqaalliance.org/adherence-measures
. Updated 2018. Accessed October 1, 2019.
13. Kini V, Ho PM. Interventions to improve medication adherence: a review. JAMA
. 2018;320(23):2461–2473. doi:.
14. Commodore-Mensah Y, Himmelfarb CR. Patient education strategies for hospitalized cardiovascular patients: a systematic review. J Cardiovasc Nurs
. 2012;27(2):154–174. doi:.
15. Nieuwkerk PT, Nierman MC, Vissers MN, et al. Intervention to improve adherence to lipid-lowering medication and lipid-levels in patients with an increased cardiovascular risk. Am J Cardiol
. 2012;110(5):666–672. doi:.
16. Walker EA, Shmukler C, Ullman R, Blanco E, Scollan-Koliopoulus M, Cohen HW. Results of a successful telephonic intervention to improve diabetes control in urban adults: a randomized trial. Diabetes Care
. 2011;34(1):2–7. doi:.
17. Rinfret S, Rodes-Cabau J, Bagur R, et al. Telephone contact to improve adherence to dual antiplatelet therapy after drug-eluting stent implantation. Heart
. 2013;99(8):562–569. doi:.
18. Zullig LL, McCant F, Melnyk SD, Danus S, Bosworth HB. A health literacy pilot intervention to improve medication adherence using Meducation® technology. Patient Educ Couns
. 2014;95(2):288–291. doi:.
19. Benjamin IJ, Kreutz R, Olsen MH, et al. Fixed-dose combination antihypertensive medications. Lancet
. 2019;394(10199):637–638. doi:.
20. Salam A, Kanukula R, Atkins E, et al. Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens
. 2019;37(9):1768–1774. doi:.
21. Park JYE, Li J, Howren A, Tsao NW, De Vera M. Mobile phone apps targeting medication adherence: quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth
. 2019;7(1):e11919. doi:.
22. Morawski K, Ghazinouri R, Krumme A, et al. Association of a smartphone application with medication adherence and blood pressure control: the MediSAFE-BP randomized clinical trial. JAMA Intern Med
. 2018;178(6):802–809. doi:.
23. Hoffmann C, Schweighardt A, Conn KM, et al. Enhanced adherence in patients using an automated home medication dispenser. J Healthc Qual
. 2018;40(4):194–200. doi:.
24. Chernew ME, Shah MR, Wegh A, et al. Impact of decreasing copayments on medication adherence within a disease management environment. Health Aff (Millwood)
. 2008;27(1):103–112. doi:.
25. Petry NM, Rash CJ, Byrne S, Ashraf S, White WB. Financial reinforcers for improving medication adherence: findings from a meta-analysis. Am J Med
. 2012;125(9):888–896. doi:.
26. Roseleur J, Harvey G, Stocks N, Karnon J. Behavioral economic insights to improve medication adherence in adults with chronic conditions: a scoping review. Patient
. 2019. doi:. Published ahead of print.
27. American Association of Colleges of Pharmacy. Medication adherence educators toolkit. https://www.aacp.org/sites/default/files/aacp_ncpa_medication_adherence_educators_toolkit_0.pdf
. Accessed October 1, 2019.
29. Million Hearts. Medication adherence: featured tools. https://millionhearts.hhs.gov/tools-protocols/medication-adherence.html#FT2019
September 30, 2019.
30. Preventive Cardiovascular Nurses Association. Customizable clinical forms. https://pcna.net/wp-content/uploads/2018/12/14-_medication_adherence.pdf?sfvrsn=2
. Accessed October 1, 2019.