Adherence Among Patients Treated With Combination vs. Separate Agents
Purpose: Adherence patterns of patients treated with a fixed-dose combination of amlodipine-benazepril versus an angiotensin-converting-enzyme (ACE) inhibitor plus a dihydropyridine calcium-channel blocker (CCB) prescribed as separate drugs were studied.
Methods: In this retrospective analysis of pharmacy claims from a managed care organization in the northeastern United States, patients who received at least two prescriptions for fixed-dose amlodipine-benazepril (n = 2839) or at least two prescriptions for an ACE inhibitor plus a dihydropyridine CCB (n = 3367) were followed over one year. Adherence, defined as the medication possession ratio (MPR), was calculated based on daily possession of the prescribed drug or drugs over the study period. To estimate the impact of overall drug burden on adherence to antihypertensive therapy, concomitant medication use was calculated as the number of American Hospital Formulary Service (AHFS) drug classes prescribed.
Results: Adherence rates among patients receiving fixed-dose amlodipine-benazepril versus an ACE inhibitor plus a dihydropyridine CCB were 87.9% and 69.2%, respectively (p < 0.0001) over a mean follow-up of 259 and 247 days, respectively. Patients received a mean 4.0 major AHFS drug classes in the amlodipine-benazepril group and 5.2 in the ACE inhibitor plus dihydropyridine CCB group. As the number of concomitant drugs increased, the difference in the MPR between the two treatment groups increased in favor of fixed-dose amlodipine-benazepril.
Conclusion: Fixed-dose amlodipine-benazepril was associated with higher adherence rates versus an ACE inhibitor plus a dihydropyridine CCB taken as two separate tablets, regardless of the number of concomitant medications prescribed.

The risks of elevated blood pressure are well established, as are the benefits of blood pressure reduction with antihypertensive therapy, yet the majority of people with hypertension fail to reach blood pressure goals. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended that consideration be given to initiating antihypertensive treatment with combination therapy in patients with a systolic blood pressure of 20 mm Hg higher or a diastolic blood pressure of 10 mm Hg higher than the target of 140/90 mm Hg (130/80 mm Hg for patients with diabetes or chronic kidney disease). Combination therapy offers the potential for more timely achievement of target blood pressure, a lower risk of adverse effects using lower doses of component agents, and greater convenience.

Many individuals with hypertension require two or more agents to reach target blood pressure. Many of these patients have diabetes, hyperlipidemia, or other conditions requiring multiple medications. Adherence to antihypertensive mono-therapy regimens has been shown to be poor in both prospective and retrospective studies and steadily decreases over time, even in populations with access to health care. Adherence is negatively affected by numerous factors, including difficulties in managing treatment regimens that include multiple medications or multiple doses. Simplification of the antihypertensive regimen may contribute to improved adherence with therapy; in turn, higher rates of adherence with antihypertensive therapy are associated with a higher likelihood of blood pressure control.

The objective of this study was to compare adherence rates of hypertensive patients prescribed fixed-dose amlodipine-benazepril with those of patients prescribed an angiotensin-converting-enzyme (ACE) inhibitor plus a dihydropyridine calcium-channel blocker (CCB) as two separate agents. This subject is of interest because of the large and growing number of fixed-dose combination products that are available for the treatment of hypertension and hyperlipidemia. In particular, this study extends the results of a previous study reporting increased adherence with fixed-dose amlodipine-benazepril compared with an ACE inhibitor and a dihydropyridine CCB prescribed as two separate agents.