Emerging evidence in NSAID pharmacology: important considerations for product selection.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain and inflammation. Emerging pharmacokinetic and pharmacodynamic evidence in NSAID pharmacology provides important criteria for selecting an appropriate NSAID. The inhibition of COX enzymes by NSAIDs affects physiologic functions in the gastrointestinal, cardiovascular, and renal systems. Of the 2 principal types of COX enzymes, COX-1 and COX- 2, the pain-relieving (anti-hyperalgesia) effects of NSAIDs are driven mainly by the inhibition of COX-2. Commonly, NSAIDs are categorized by in vitro selectivity (ie, the ratio of the NSAID concentrations required for inhibition of COX-1 and COX-2) as selective or nonselective. Theoretically, the concept of selectivity is convenient; however, the actual relative inhibition of COX-1 and COX-2 isoenzymes measured in vitro is dose-dependent. As a result, the predicted in vivo reduction of prostanoidinduced hyperalgesia and the expected adverse effects of an NSAID are dose dependent. Individual NSAIDs also differ on pharmacokinetic and pharmacodynamic parameters such as the absorption, time to availability of drug at the site of inflammation, and persistence at the site of inflammation. NSAIDs with longer half-life durations may offer longer durations of analgesia due to continued COX enzyme inhibition, but may provide less opportunity for recovery of COX activity between doses than NSAIDs with shorter half-lives. Understanding these pharmacokinetic and pharmacodynamic factors informs selection of an appropriate NSAID among this heterogeneous class of drugs.

Adherence patterns among patients treated with fixed-dose combination versus separate antihypertensive 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.

Relationship of blood pressure control to adherence with antihypertensive monotherapy in 13 managed care organizations.

OBJECTIVE: This study was conducted to evaluate the relationship between medication compliance and blood pressure (BP) control among members of 13 managed care organizations with essential hypertension (HTN) who received antihypertensive monotherapy for at least 3 pharmacy claims prior to the blood pressure measurement. METHODS: This was a retrospective review of medical and pharmacy claims over a 4-year period (1999-2002) from 13 U.S. health plans. Data were collected by trained health professionals from randomly selected patient medical records per Health Plan Employer Data and Information Set (HEDIS) technical specifications. Patients were selected if they (1) had received monotherapy or fixed-dose combination therapy (administered in one tablet or capsule) during the time BP was measured (thus those with no BP drug therapy were excluded); (2) had received 3 or more antihypertensive pharmacy claims for the antihypertensive drug therapy prior to BP measurement; and (3) had one or more antihypertensive pharmacy claims after BP was measured. Control of BP was defined according to guidelines of the Sixth Report of the Joint National Committee (JNC 6) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (<140/90 mm Hg, or <130/85 mm Hg for patients with diabetes). Medication adherence was measured using the medication possession ratio (MPR), and MPR was used to classify patients into 3 adherence levels: high (80%-100%), medium (50%-79%), and low (<50%). The relationship between medication adherence and BP control was assessed using a logistic regression model. RESULTS: There were 1,017,181 patients with a diagnosis of HTN in medical claims data from which 10,734 (10.6%) were randomly selected for chart review. There were 1,032 patients (9.6%) in the sample who had a diagnosis of HTN but who were excluded because they had no HTN drug therapy. Of the total 9,894 patients (92.2%) who were excluded from the sample, 3,029 patients (28.2%) met all other inclusion criteria but were receiving more than one HTN drug. Of the 840 patients on HTN monotherapy, the mean age was 59 12.2 years; 422 (50%) were women, 16% had diabetes, and 43% had dyslipidemia. The monotherapy HTN drug was an angiotensin-converting enzyme inhibitor (27% of patients), calcium channel blocker (22%), beta-blocker (20%), or diuretic (11%). Of the 840 patients, 629 (74.8%) were determined to have high medication adherence, 165 (19.6%) had medium adherence, and 46 (5.5%) had low adherence. Approximately 270 (43%) of high adherence patients achieved BP control compared with 56 (34%) and 15 (33%) patients with medium and low adherence, respectively. High-adherence patients were 45% more likely to achieve BP control than those with medium or low compliance after controlling for age, gender, and comorbidities (odds ratio=1.45; P =0.026). CONCLUSION: These results demonstrate that 75% of these health plan members with a diagnosis of essential HTN who were selected for receipt of at least 4 pharmacy claims for HTN monotherapy exhibited high medication adherence. However, only 43% of high-adherence patients attained their target (JNC 6) blood pressure goal compared with 33% to 34% of patients with medium or low adherence to antihypertensive monotherapy.

Appropriate antibiotic therapy for community-acquired respiratory tract infections.

Respiratory tract infections (RTIs) are expensive for MCOs and cause significant morbidity among their members. Although awareness of resistance to antibiotics is increasing, antibiotic selection for community-acquired RTIs remains largely empiric. When making formulary decisions, Pharmacy and Therapeutics Committees may want to consider the spectrum of coverage that an antibiotic provides and its vulnerability to resistance development. Through appropriate formulary management and provider education, MCOs can promote successful clinical and economic outcomes. This article examines the current status of antibiotic therapy for community-acquired RTIs and encourages the incorporation of new parameters into MCO formulary decision processes.