Drug Compliance and Persistence — A Major Public Health Problem

Abstract & Commentary

By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.

Synopsis: Patients who adhered to prescribed anti-hypertensive medication experienced a significantly decreased risk of acute cardiovascular events, yet only 6 months after diagnosis, only 8.1% of patients were classified as having high adherence, 40.5% demonstrated intermediate adherence, and 51.4% demonstrated low adherence to prescribed medication regimens.

Source: Mazzaglia G, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation 2009;120: 1598-1605.

Hypertension (HBP) has been demonstrated to be one of the most preventable causes of cardiovascular disease morbidity and mortality.1 Besides decreases in the incidence of stroke (by 34%) and ischemic heart disease (by 21%), multiple clinical trials have clearly reported that an appropriate reduction in HBP is also associated with significant decreases in the incidence of congestive heart failure and renal failure irrespective of age, gender, race or ethnicity, type of antihypertensive used, or severity of hypertension.2-4

Despite these compelling data, the National Health and Nutrition Examination Survey recently reported that roughly 40% of hypertensive individuals were untreated and 65% did not have their HBP controlled (to a blood pressure level < 140/90 mm Hg).5 One of the main reasons for these poor long-term results is the overall lack of patient compliance and persistence with drug therapy. Antihypertensive drug therapy discontinuation rates range from 5% to 10% per year and have been reported to climb to 50%-60% of patients within 6 months after initiation of therapy.6,7

Mazzaglia and his colleagues explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. They selected 18,806 newly diagnosed and treated hypertensive patients older than age 35 years who were initially free of cardiovascular diseases. They evaluated the risk of developing acute cardiovascular events in patients who had high adherence (proportion of days covered ≥ 80%), intermediate adherence (proportion of days covered = 40%-79%) and low adherence (proportion of days covered ≤ 40%) to prescribed medication. Six months after the diagnosis of HBP and initiation of drug therapy, only 8.1% demonstrated high adherence, 40.5% were classified as intermediate adherence, and 51.4% of patients were at the low adherence level. Only high adherence to antihypertensive medication therapy was associated with a relevant decrease in acute cardiovascular events.


Increasing numbers of obese and/or aging patients are among the several important factors responsible for the increasing rate of HBP, which is now resulting in more office visits annually to primary care physicians than occurs with any other medical condition.8 Unfortunately, medical care for HBP in the United States is inadequate often because of a failure by physicians to follow guidelines, but especially because of poor patient compliance with drug therapy, which is due to many factors.

For example, it must be recognized that health literacy (i.e., the degree to which individuals have the capacity to obtain, process, and understand basic health information and health services needed to make appropriate health decisions) in general is extremely poor in that only 36% of U.S. adults possess basic or above basic health literacy skills9 and, among the elderly, more than 50% of patients age 80-84 years and more than 70% of patients age 85 years and older have marginal or limited health literacy.10 Health literacy in the United States is so poor that only 13% of patients understand the meaning of "terminal," only 35% understand "orally," only 18% understand "malignant," only 52% understand "take every six hours," 68% are unable to understand blood sugar values, fully 27% are unable to understand fourth-grade level instructions such as "take medicines on an empty stomach," and up to 100% of subjects did not understand a statement concerned with patient Medicaid rights written at a 10th grade level.8 Adherence to a prescribed antihypertensive medication regimen is complicated by the fact that most patients with HBP require three or more medications to reach appropriate blood pressure goals.

Most medical caregivers and many physicians often do not have the education, training, skill, and (especially) the time to communicate with and therefore to properly educate patients on the importance of properly taking medications. This universal failing is not just with antihypertensive medication, but also with almost all drugs that are taken chronically and is equally true of medications used for control of abnormal serum lipids. Numerous attempts at improving drug therapy compliance have been made including developing motivational communications, lifestyle and disease educational brochures, telephone and device reminders, dosage modification techniques, and medication diaries, but the results with these multiple approaches have been only marginally successful. More recently patients have been enrolled in very expensive and elaborate programs through which they receive regular communications, educational data, and refill letters, and various incentive programs have also been used to reward patients for adhering to their medication regimens — all of these techniques have been, at best, only minimally successful.

Newer quite creative education and behavior modification systems have been created and are being used in early demonstration projects. Hopefully, these efforts at behavior modification will change the perceptions and attitudes of patients to the degree that they will actually feel uncomfortable if their medications are unavailable to them or if, by mistake, they forget to take their prescribed drugs. Mazzaglia and his associates have again demonstrated the medical importance of adequate antihypertensive therapy and have highlighted advanced methods for improving patient compliance and persistence, which may soon be available to help patients achieve appropriate blood pressure goals.


1. Ezzati M, et al; Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of disease. Lancet 2002;360:1347-1360.

2. Law M, et al. Lowering blood pressure to prevent myocardial infarction and stroke: A new preventive strategy. Health Technol Assess 2003;7:1-94.

3. Mancia G, et al; ESH-ESC Task Force on the Management of Arterial Hypertension. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension. J Hypertens 2007;25:1751-1762.

4. Chobanian AV, et al. Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-1252.

5. Cutler JA, et al. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 1999-2004. Hypertension 2008;52:818-827.

6. Mazzaglia G, et al. Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: A retrospective cohort study in primary care. J Hypertens 2005;23:2093-2100.

7. Burke TA, et al. Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice. J Hypertens 2006;24:1193-1200.

8. Williams MV. Recognizing and overcoming inadequate health literacy, a barrier to care. Cleve Clin J Med 2002;69:415-418.

9. Kunter M, et al. The health literacy of America's adults: Results from the 2003 national assessment of adult literacy (NECS 2006-483). Washington, DC: U.S. Department of Education, National Center for Education Statistics; 2006.

10. Williams, MV, et al. Recognizing and overcoming inadequate health literacy, a barrier to care. Cleve Clin J Med 2002;69:415-418.