Impact of Drug Class on Long-Term Adherence to Antihypertensives

Abstract & Commentary

By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman serves on the speakers bureau for Forest Laboratories.

Synopsis: Important differences in adherence to antihypertensive drug therapy occurred depending on the drug class prescribed with the lowest adherence noted to occur with diuretics and beta-blocker therapy and the highest adherence was observed with ARB or ACI therapy.

Source: Kronish IM, et al. Meta-analysis: Impact of drug class on adherence to antihypertensives. Circulation 2011;123:1611-1621.

Hypertension (HBP) is the most common chronic illness in developed countries, affecting more than 50% of the U.S. population, and, therefore, is one of the most important risk factors for cardiovascular disease.1 Lowering blood pressure in hypertensive individuals has clearly been demonstrated to significantly reduce coronary events by 21%, strokes by 34%, incidence of congestive heart failure and renal failure, and also overall mortality2,3 irrespective of age, race, gender, ethnicity, or HBP severity. In addition to changing harmful lifestyle factors in hypertensive individuals, medical management of HBP remains the cornerstone of therapy.4 Clinical practice guidelines5 have been developed to assist physicians in selecting the proper antihypertensive medications. However, because of selection bias, run-in periods, and lack of effective behavior reinforcement, the published adherence to medication statistics may not be representative of the true adherence in real-world settings.6 Among the many reasons for poor long-term results in the treatment of HBP are the overall lack of patient compliance and persistency with drug therapy, leading to antihypertensive drug therapy discontinuation rates ranging from 5% to 10% per year, which results in drug discontinuation in 50%-60% of patients only 6 months after initiation of therapy.7,8

Because observational studies have suggested that there are differences in adherence to antihypertensive medications in different drug classes, Kronish and his colleagues performed a meta-analysis to quantify the association between antihypertensive drug class and adherence in clinical settings.9 Their comprehensive search yielded 115 unique articles relating the predictors of adherence to antihypertensive medication, and they selected 17 articles from this group that met their inclusion criteria. They determined that there was a significant relationship between adherence to antihypertensive medication and drug class. Patients who were prescribed diuretics and beta-blockers (BBs) had the lowest adherence to antihypertensive drug therapy, whereas patients prescribed angiotensin receptor blockers (ARBs) were approximately twice as likely to have good adherence. Angiotensin converting enzyme inhibitors (ACIs) appeared to have the second-best level of adherence followed by calcium-channel blockers (CCBs). In summary, patients prescribed diuretics and BBs demonstrated the lowest adherence to antihypertensive medication, especially compared with those patients who were receiving ARBs and even to those who were being treated with ACIs or CCBs.


Although rates of blood pressure control are improving in the United States, well more than 50% of hypertensive patients in the United States continue to have blood pressures above recommended levels1 resulting in an unnecessary increase in cardiovascular events and contributing to runaway health care costs.10,11 The increasing numbers of obese and/or aging patients and poor health literacy are among several important factors responsible for the increasing rate of HBP which is now resulting in more office visits annually to primary care physicians than any other medical condition.12 Adherence to a prescribed antihypertensive medical regimen also is complicated by the fact that most patients with HBP often require three or more medications in order to reach appropriate blood pressure goals. Another factor to be considered in antihypertensive drug therapy is the class of drugs that is used. The finding of the meta-analysis performed by Kronish and colleagues9 clearly emphasizes that physicians should pay special attention to adherence in patients who are prescribed diuretics and/or BBs because, although rates of adherence are suboptimal for all drug classes, they are particularly low for patients who've been prescribed diuretics and/or BBs. Diuretics may be discontinued by patients because the drugs may cause urinary frequency, erectile dysfunction, fatigue, muscle cramps, and/or electrolyte imbalance, whereas BBs may result in hypotension and/or bradyarrhythmias. Some studies have demonstrated differences in physician perceptions of the effectiveness and tolerability of antihypertensive medication in separate classes,10 which may explain why some of the noted differences in the class of antihypertensive drug selected may be related to drug selection factors rather than due to the drug class itself. Physicians will frequently select certain classes of antihypertensive drugs based on pharmaceutical marketing practices as well as their personal experience with these agents over the years and, therefore, the results of drug class selection may be biased by physician preferences, which undoubtedly are influenced by many factors.

Finally, it must be recognized that drug adherence to any class of drug (i.e., antihypertensive, lipid-lowering agents, etc.) will vary considerably based on the physician-patient interrelationship. Some physicians provide an increased level of patient education and careful follow-up, which encourages drug adherence unrelated to the class of antihypertensive drug that is used. Appropriate educational activities — including in-depth discussions regarding the need for treatment of HBP and the benefits that will follow, frequent office and telephone follow-ups, and home blood pressure monitoring — will help bring the patient into an active therapeutic environment and will improve drug therapy compliance. It often is difficult to get patients involved in their own therapy but it is the most effective way to improve patient compliance in all drug therapy. Unfortunately, most medical caregivers and many physicians often do not have the education, training, and skills — and especially the time to communicate — to properly educate patients on the importance of taking their medications as prescribed. Whatever the class of antihypertensive medication selected, all physicians should be aware of the critical need for them to spend more time with their patients to educate and motivate them to appropriately modify their behavior with respect to the medications that have been prescribed to them.


1. Egan BM, et al. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA 2010;303:2043-2050.

2. Gueyffier F, et al. Antihypertensive drugs in very old people: A subgroup meta-analysis of randomized controlled trials. INDANA Group. Lancet 1999;353:793-796.

3. Ogden LG, et al. Long-term absolute benefit of lowering blood pressure in hypertensive patients according to the JNC VI risk stratification. Hypertension 2000;35: 539-543.

4. Bernier M. Medication adherence and persistence as the cornerstone of effective antihypertensive therapy. Am J Hypertens 2006;19:1190-1196.

5. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA 2003;289:2560-2572.

6. Andrade SE, et al. Discontinuation of anti-hyperlipidemia drugs — do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995;332: 1125-1131.

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

9. Kronish IM, et al. Impact of drug class on adherence to antihypertensives. Circulation 2011;123:1611-1621.

10. Ho PM, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006;166:1842-1847.

11. McCombs JS, at al. The costs of interrupting antihypertensive drug therapy in a Medicaid population. Med Care 1994;32:214-226.

12. Williams MV. Recognizing and overcoming inadequate health literacy, a barrier to care. Cleveland Clinic J Med 2002;69:415-417.

13. Horne R, et al. Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999;47:555-567.