A Retrospective Database Analysis of Prescribing Patterns

Abstract and Introduction

Angiotensin II receptor blockers (ARBs), one of the fastest-growing drug classes for hypertension, have shown some differences in use in terms of daily dose, which can translate into increased costs and decreased compliance. The prescribing patterns for all products in the ARB class, including both single entities and combinations with hydrochlorothiazide, were investigated by calculating daily average consumption (DACON) scores for each agent. Data were obtained from medical and pharmacy claims of Horizon Blue Cross Blue Shield of New Jersey for a 7-month study period. A total of 13,391 members met the inclusion criteria and generated 82,640 pharmacy claims for ARB products for analysis. Valsartan was the most frequently prescribed ARB, followed by losartan. ARBs were more likely to be prescribed alone than in combination with hydrochlorothiazide. Losartan accounted for a higher proportion of total annualized costs (based on average wholesale price), according to the DACON score. Because ARB and ARB-plus-diuretic combination products contain many of the higher-cost antihypertensive agents, small differences in DACON scores may translate into a great impact on pharmacy costs to the health plan, as well as compliance issues from the patient's perspective.

The newest class of available antihypertensive agents is angiotensin II receptor block ers (ARBs). Recently, several ARBs proved beneficial in the management of cardiovascular disease, diabetic nephropathy, and heart failure and are now approved for conditions beyond their initial indication for hypertension. Utilization data at Horizon Blue Cross Blue Shield of New Jersey have indicated that β-blockers are the most commonly used medication for hypertension, followed by angiotensin-converting enzyme inhibitors, calcium channel blockers, and ARBs. An analysis of ARB utilization has indicated prescribing differences in daily doses that may contribute to additional costs and decreased compliance. For this reason, understanding how these drugs are prescribed is of paramount importance to MCOs.

All ARBs initially received FDA approval for the treatment of essential hypertension. While data have shown that these agents effectively lower blood pressure, duration of the antihypertensive effect may not always be sustained for a full 24-hour period. Thus, twice-daily dosing of some agents may be necessary. To assess whether a drug can be dosed once daily, a drug's trough: peak ratio is calculated. This ratio evaluates the maximum plasma concentration (peak) achieved after a single dose and compares it with the minimum concentration reached immediately before the next dose is given (trough). If a drug's trough: peak ratio is less than 0.5, once-daily dosing is inappropriate.

The trough:peak ratios for most ARBs are in excess of 0.5 ( Table 1 ). However, the value of losartan (Cozaar) is 0.55, which approaches the limit for once-daily dosing. For this reason, it is stated in the prescribing information for losartan that this product can be given once or twice daily. Eprosartan (Teveten) and candesartan (Atacand) also can be dosed once or twice daily, but dos-ing decisions are up to physicians, who base such decisions on each patient's response to the medication. The ARB valsartan (Diovan) has an additional indication for use in heart failure, for which twice-daily dosing is recommended.

While most ARBs are dosed once daily and the majority of clinicians consider these products effective for a 24-hour period in most patients, a review of pharmacy claims data from Horizon Blue Cross Blue Shield of New Jersey indicated that ARBs and ARB combination products are being used in excess of once daily. Because even nominal use of a product in excess of once daily can have a significant financial impact when multiplied by 150,000 prescriptions annually, we undertook a retrospective claims data analysis to assess prescribing patterns for the ARB class among our members.

Cite this: A Retrospective Database Analysis of Prescribing Patterns for Specific Angiotensin Receptor Blockers - Medscape - Jan 01, 2005.

Sidebar: Editorial Comment: Off-Label Use Is A Common Though Underexamined Practice

The concept of off-label prescribing, first described to the FDA in 1972, was primarily derived from the 1938 Federal Food, Drug, and Cosmetic Act and its 1962 amendments.^[1] Although the FDA strictly regulates how drugs are advertised and promoted to physicians, these regulations do not preclude a physician's prescribing drugs at dosages different from those indicated or for a condition(s) not described in the package inserts. Often, physicians decide to prescribe a drug for an off-label use or at an unindicated dosage after evaluating available clinical information, such as evidence from peer-reviewed literature and their own observations of patients for whom the drug was prescribed.

Off-label prescribing is a relatively common practice. The American Medical Association estimates that about 50% of all prescriptions in the United States are written for unapproved purposes.^[2] There is no evidence that off-label prescribing results in more frequent adverse outcomes. However, there is a need for more studies of off-label prescribing. Such studies should provide clear descriptions of the methods used to compare drugs or outcomes. In this article, Dr Jan and colleagues provide such an example, explaining how off-label use of angiotensin II receptor blockers (ARBs) is determined and how such practice may increase costs and decrease compliance.

The study findings point to losartan as being the ARB most frequently prescribed for more than once-daily dosing, even though labeling for losartan calls for once-daily initial dosing. In future studies, it may help to differentiate between prescriptions for initial dosing and refill prescriptions. It might be the case, for example, that adjustments in the dosage of losartan are recommended for at least weekly intervals, and patients may undergo a few dosage adjustments during a maximum interval of 7 months.^[3] In addition, some monitoring dosages could have been included as part of the data intended to show only initial dosing. The ramification is that the once-daily dosing parameter needs to be put in context, because inadequate control of hypertension in patients taking losartan can call for dividing the same total daily dose into twice-daily dosing.^[4] This may explain why losartan and eprosartan—the only ARB agents in the study that have been approved for twice-daily dosing and that have proved to produce larger trough responses than once-daily dosing at the same total dose—had the 2 highest percentages for patients dosed more than once a day.^[4,5]

These study results are important but need to be interpreted in light of the limitations in methodology.

Fadia T. Shaya, PhD, MPH,* Jung Kim^†
*Assistant professor and associate director of the Center on Drug and Public Policy, University of Maryland School of Pharmacy, Baltimore
^†PharmD student, University of Maryland School of Pharmacy, Baltimore

References

Torres A. The use of Food and Drug Administration–approved medications for unlabeled (off-label) uses: the legal and ethical implications. Arch Dermatol. 1994;130:32-36.
Gorman C. Double-duty drugs: approved medications are being widely prescribed for unapproved uses. Time. September 18, 1995:96.
Klasco RK, ed. DRUGDEX System. Greenwood Village, Colo: Thomson Micromedex; 2004.
Cozaar [package insert]. Whitehouse Station, NJ: Merck & Co; 2003.
Teveten [package insert]. Bridgewater, NJ: Biovail Pharmaceuticals; 2003.

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A Retrospective Database Analysis of Prescribing Patterns for Specific Angiotensin Receptor Blockers

Abstract and Introduction

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References

Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar: Editorial Comment: Off-Label Use Is A Common Though Underexamined Practice

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