Prescription Drug Adherence: A "Challenge" for So Many…

JANUARY 01, 1970
Marile L. Santamarina, MS, PharmD, CPh, and Elizabeth C. DiMaggio, PharmD Candidate

Dr. Santamarina is an assistant professor of pharmacy practice at Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, Florida. Ms. DiMaggio is a fourth-year PharmD candidate at Palm Beach Atlantic University.

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Despite the abundance of clinically effective prescription medications for the treatment of chronic diseases, achieving optimal clinical goals is still elusive.1,2 Achieving suboptimal outcomes in the presence of effective medications has highlighted the ever-present problem of poor medication compliance.3 Data show that only 50% of patients take their medications as originally prescribed.4,5 Poor compliance in chronic diseases such as hypertension, type 2 diabetes, and dyslipidemia, where a lifelong medication commitment is needed to achieve adequate control and prevent long-term complications, is a wellknown public he alth problem.6

Health care providers prefer the term adherence over compliance.3 Adherence implies that both the health care provider and the patient are actively involved in choosing the best regimen for the patient. In contrast, compliance implies that the patient passively follows the health care provider’s orders.3 Poor medication adherence can cause serious clinical and economic consequences for the patient and for society at large7,8—called “America’s other drug problem” by the National Council on Patient Information and Education (NCPIE), it is a costly public health problem.9 Data from the 2007 NCPIE report show that poor adherence costs the United States about $177 billion annually—$47 billion per year in drug-related hospitalizations, a 40% increase in nursing home admissions, and an added $2000 in physician visits per year.9 Poor adherence can be described in multiple ways, such as forgetting doses of medication, taking an incorrect dose, stopping treatment sooner than prescribed, and taking the medication at an incorrect time. Some clinical trials describe adequate adherence as >80%,3 while others describe adequate adherence at 95%.10 Currently, no unified gold standard exists to measure adherence. Clinical efficacy data demonstrate that therapeutic benefits of medications will be attained only if patients follow the prescribed regimen, however.11

Studies have shown that patients suffering from chronic conditions exhibit lower adherence than patients suffering from acute conditions,3 with adherence declining drastically during the first several months of therapy.4,12 For example, one study reflected that statin adherence dropped to 50% after a 6-month regimen was initiated.13 This is a critical factor to keep in mind when reviewing adherence rates for some of the most important and prevalent chronic conditions: type 2 diabetes and hypertension.

According to the American Diabetes Association standards of medical care, only 37% of adult patients with diabetes reach the recommended glycosylated hemoglobin A1C goal of 7%.14 Abundant data indicate that patients with diabetes not reaching glycemic control may suffer serious long-term clinical consequences, such as retinopathy, nephropathy, and peripheral neuropathies.15 Perhaps one of the reasons why such a small percentage of patients reach glycemic goal relates to poor medication adherence. Rubin16 reported oral adherence ranging from 65% to 85% in patients with type 2 diabetes, and 60% to 80% for patients using insulin. Newly treated patients with type 2 diabetes had a 54% adherence rate.17 Some studies report adherence rates as low as 36% in patients with type 2 diabetes, however.18,19

Low adherence to antiglycemic agents is associated with increased medical costs and hospitalization risk (defined as the chance of having ≥1 hospitalizations during a 1-year period). 8 Patients with diabetes with <60% adherence had annual medical costs of $6522 and hospitalization risk of 25%. Patients who were 80% or more adherent had annual medical costs estimated at $4570 and hospitalization risk of 13%.8

Patients with uncontrolled hypertension and poor medication adherence fared similar to those with type 2 diabetes. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends a blood pressure goal of <140/90 mm Hg in individuals with uncomplicated hypertension.20 Blood pressure goals are lower (<130/80 mm Hg) for individuals with diabetes or chronic kidney disease.20 An estimated two thirds of US adults with hypertension are untreated or undertreated. Although hypertension is generally considered an asymptomatic condition, it is a significant risk factor for fatal and nonfatal cardiovascular events.21 Randomized clinical trials have shown that antihypertensive pharmacotherapy decreases the risk of stroke by approximately 30%, coronary heart disease by 10% to 20%, and congestive heart failure by 40% to 50%.22 Approximately 45 million people treated with antihypertensive medications report 40% nonadherence. 23 According to Sokol et al,8 patients with hypertension having <60% medication adherence had a total annual medical cost of $5297 and a 24% hospitalization rate, while those having ≥80% adherence experienced annual medical costs of $4871 and a 19% hospitalization risk.

Given the serious clinical and economic consequences of poor medication adherence, it is important to identify contributory factors. Some reasons include: patients are not convinced they need treatment, especially when the condition treated is asymptomatic with no immediate apparent benefits12,13; patients do not accept that the severity of their condition requires medication24; poor communication exists between the physician and the patient25; the patient fears adverse events25; medications are too costly26; numerous medications are already prescribed3; and the patient is being treated by multiple physicians.3 Because medication nonadherence is affected by multiple factors, including those that are educational and behavioral, a multidisciplinary approach appears to be the most effective means toward improvement.27

Important interventions to improve medication adherence include: (1) patient education, (2) improving communication between physician and patient, (3) decreasing medication dosing frequency, and (4) decreasing pill burden by using fixed-dose combination medications.

First, patients need to be educated about their condition, present prognosis, and medication adherence for preventing long-term disease complications. Individuals who do not perceive their disease to be a threat exhibit 1.5 times greater nonadherence; individuals who perceive their malady to be treatable with their current medication have 2.5 times greater adherence.28

Second, good communication between the health care provider and patient will ensure that patients understand the details of their therapy. Neuwirth29 reported that physicians’ instructions, coupled with patients’ motivation, resulted in improved clinical outcomes and increased medication adherence.

Third, clinical trials have shown that decreasing the frequency of daily dosing improves adherence.30 Patients with hypertension treated with a once-daily dosing regimen had an 84% adherence rate, whereas adherence of patients with a 3-times-daily regimen decreased to 59%.31 When optimal adherence, defined as no medication omission, was studied in patients with type 2 diabetes, adherence showed a dramatic decline with increased daily dosing. Optimal compliance was achieved by 79% of patients with diabetes on a once-daily regimen, 66% on twice-daily dosing, and 36% on 3-times-daily dosing.32

Lastly, and perhaps most beneficial, is the use of fixed-dose combination medications. As most patients with chronic conditions require multiple agents to attain therapeutic goals,33-35 fixed-dose combination medications allow patients to decrease their pill burden,36 improve adherence,36 and gain the economic benefit of a single copayment.37

A fixed-dose combination product frequently combines medications from different drug classes with varied mechanisms of action into a single tablet for added synergy and to improve adherence. Studies have ex amined different combinations of products to achieve therapeutic goals in chronic conditions. In a trial that included patients with diabetes, those receiving a glyburide/ metformin combination tablet experienced a significant drop in A1C (2.02%) when compared with 1.49% for patients receiving coadministration of glyburide and metformin (P <.0001). In addition, adherence was significantly higher in the glyburide/metformin tablet group at 84% versus 76% (P <.0001) in the glyburide and metformin coadministration group.38 Similar adherence results were obtained with combination antihypertensive medications. In a retrospective analysis of pharmacy claims from a managed care organization, adherence rates over a 12-month period were compared in patients prescribed fixed-dose amlodipine/ benazepril with those in patients prescribed an angiotensin-converting enzyme inhibitor plus a calcium channel blocker.39 Adherence rates were significantly higher in patients receiving fixed-dose amlodipine/benazepril at the 12-month follow-up (88% vs 69% with separate agents; P <.0001), and during each 3-month assessment period (P <.0001).39

Increasing the rate of medication adherence for chronic conditions will improve clinical outcomes, lower health care costs, and reduce morbidity and mortality. Pharmacists’ knowledge of medications, counseling skills to decrease pill burden, ability to modify dosing regimens, and recommendation of the most appropriate and affordable fixed-dose products provides a unique opportunity for pharmacists to optimize medication use in patients suffering from chronic conditions.





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2. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.

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7. Straton IM, Adler AI, Neail HA, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.

8. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on hospitalization risk and healthcare cost. Med Care. 2005;43(6):521-530.

9. Enhancing Prescription Medicine Adherence: A National Action Plan. National Council on Patient Information and Education. August 2007. Accessed October 22, 2009.

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11. Poor medication adherence increases healthcare costs. Pharmacoeconomics Outcomes News. 2005;480:5.

12. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndrome. JAMA. 2002;288(4):462-467.

13. Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288(4):455-461.

14. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13-S61.

15. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317(7160):703-713.

16. Rubin RR. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med. 2005;118:27S-34S.

17. Hertz RP, Unger AN, Lustik MB. Adherence with pharmacotherapy for type 2 diabetes: a retrospective cohort study of adults with employer-sponsored health insurance. Clin Ther. 2005; 27(7):1064-1073.

18. Rozenfeld Y, Hunt JS, Plauschinat C, Wong KS. Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care. 2008;14(12):71-75

19. Odegard PS, Capoccia K. Mediation taking and diabetes: a systematic review of the literature. Diabetes Educ. 2007;33(6):1014-1029.

20. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252.

21. Wang TJ, Vasan RS. Epidemiology of uncontrolled hypertension in the United States. Circulation. 2005;112(11):1651-1662.

22. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA. 2003;289(19):2534-2544.

23. Sanz G, Fuster V. Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population. Nat Clin Pract Cardiovasc Med. 2009;6(6):101-110.

24. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.

25. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):1349-1357.

26. Nag SS, Daniel GW, Bullano MF, et al. LDL-C goal attainment among patients newly diagnosed with coronary heart disease or diabetes in a commercial HMO. J Manag Care Pharm. 2007;13(8):652-663.

27. McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA. 2002;288(22):2868-2879.

28. van Servellen G, Chang B, Garcia L, Lombardi E. Individual and system level factors associated with treatment nonadherence in human immunodeficiency virus-infected men and women. AIDS Patient Care STDS. 2002;16(6):269-281.

29. Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations. J Gen Intern Med. 2004;19(6):638-645.

30. World Health Organization. Adherence to long-term therapies. Evidence for action, 2003. Accessed October 24, 2009.

31. DiMatteo MR, Haskard KB, Williams SL. Health beliefs, disease severity, and patient adherence: a meta-analysis. Med Care. 2007;45(6):521-528.

32. Neuwirth ZE. An essential understanding of physician-patient communication. Part II. J Med Pract Manage. 1999;15(2):68-72.


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