Fixed-Dose Combination Therapy for Hypertension Improves Compliance,Lowers Costs
Patients with hypertension treated with both an angiotensin-converting enzyme (ACE) inhibitor and a calcium-channel blocker (CCB) are more likely to take their medications on schedule if the drugs are combined in a single fixed-dose pill, according to a recent study of a large managed-care population. The retrospective analysis also showed a lower combined cost of medications and clinical care for patients on fixed-dose combination therapy than for those taking the drugs in separate pills.The greater compliance with fixed-dose combination therapy was independent of the severity of their clinical condition, reported Omar Shoheiber, PharmD (Tricord, Princeton, NJ), and Paul M. Pinkston, PharmD (Novartis, East Hanover, NJ) at the November, 2002, scientific meeting of the American Society of Health-System Pharmacists. And with increasing age, the gap in compliance between patients on the 2-pill regimen widened, they reported.
Patients with hypertension are notorious for frequently not fully complying with their prescribed drug regimens.The cost of multiple drugs and the complexities of taking them throughout the day are thought to be part of the cause. Such undercompliance likely contributes to the low overall rate of blood-pressure (BP) control among patients on antihypertensive therapy.
In addition, shortfalls in compliance could potentially increase in the coming years as current treatment recommendations call for many patients to take more medications earlier in the course of antihypertensive therapy. The recently released updated management guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) cite considerable data suggesting that most patients with hypertension will require multiple drugs to achieve their BP goals (Chobanian AV, et al.
2003;289:2560-2571).Compliance and cost issues are therefore integral to efforts to improve the overall rate of BP control among hypertensives. In the recent compliance study conducted by Tricord and referenced earlier, investigators reviewed medical and pharmacy claims from more than 6500 adults enrolled in a large managed care organization who were on an ACE inhibitor and a CCB and initially given 2-months or more supply of drug therapy.The patients had been prescribed either a fixed-dose combination of benazepril and amlodipine (Lotrel
or an ACE inhibitor plus a dihydropyridine CCB as separate medications. Patient compliance with prescribed therapy throughout the next year or more was measured according to the "medication possession ratio" or MPR.This was defined as the proportion of days the patients were in possession of the correct daily medication dose of both agents, as determined from the regularity of prescription refills.Compliance during the follow-up period was significantly greater among the patients
assigned to fixed-dose combination therapy.The MPR for those taking Lotrel was 81.0%, as compared to 73.7% for patients taking the drugs separately (
< .0001).Put another way, the patients on Lotrel were compliant with both drugs in their prescribed regimen for 27 more days of the year. In addition, compliance increased with age among the patients on Lotrel but increased only slightly for the 2-pill patients, with the difference between them significant for almost every age group by decade (Table 2).
More patients in the 2-pill group had at least 2 other disorders in addition to hypertension,
including ischemic heart disease, heart failure, or diabetes. But the single-pill regimen?s compliance advantages held steady regardless of the number of comorbidities (Table 3).
In addition, the cost of clinical care was less for patients on the Lotrel regimen. In a follow-up analysis based on data from 88% of the original cohort of 6541 patients, those on the single-pill regimen on average incurred significantly lower combined pharmacy and medical services costs. In addition, those same costs were consistently lower for patients on Lotrel when patients were stratified according to the severity of their overall cardiovascular disease status (Table 4).
Current treatment recommendations support the use of fixed-dose combination therapy to control costs and lower the risk of dosing-related adverse effects, the researchers noted. "These agents," they concluded, "may also provide convenience for patients, thereby increasing compliance with antihypertensive therapy."