Adherence and Dosing Frequency of Common Medications for Cardiovascular Patients
Published Online: March 16, 2012
Jay P. Bae, PhD; Paul P. Dobesh, PharmD; Donald G. Klepser, PhD, MBA; Johnna D. Anderson, MS; Anthony J. Zagar, MS; Patrick L. McCollam, PharmD; and Molly E. Tomlin, MS
Cardiovascular disease (CVD) continues to be the leading cause of mortality in the western world. In the United States alone, more than 830,000 people die each year from CVD, which accounted for 34.3% of all deaths in 2006.1 The prevalence of CVD in the US population is staggering, with 17.6 million, 5.8 million, and 6.4 million individuals living with coronary heart disease, heart failure, or a history of stroke, respectively.1 These numbers are likely to rise with the increasing elderly population, which is anticipated to be 20% of the US population by 2030.2
Over the last decade, numerous clinical trials of medications have demonstrated signifi cant benefi t in treating patients with CVD and associated risk factors, such as diabetes mellitus, and are now highly recommended in clinical guidelines.3-7 For these medications to provide their benefi ts, patients need to be adherent to the prescribed regimen. Adherence, as defi ned by the International Society for Pharmacoeconomics and Outcomes Research, is “the degree or extent of conformity to the recommendations about day-to-day treatment by the provider with respect to the timing, dosage, and frequency. It may be defi ned as ‘the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen.’”8 While this is one defi nition of adherence, it can basically be explained as “Does the patient take the medication as prescribed?”
Despite evidence of signifi cant clinical benefit, for patients with CVD, adherence is often suboptimal.9-16 It has been estimated that 40% to 50% of patients with CVD may be nonadherent, and this reduction in adherence may be seen at approximately 3 to 6 months of therapy.10-12 Medication nonadherence is a commonly recognized source of adverse patient outcomes and use of healthcare and associated costs.16,17 Studies have demonstrated that nonadherence to therapies for hypertension, dyslipidemia, or chronic stable angina results in greater morbidity, increased risk for hospitalization, or greater mortality. 14,18-25 For example, data from the PREMIER (Prospective Registry Evaluating Myocardial Infarction: Events and Recovery) registry have demonstrated that lack of adherence with the antiplatelet agent clopidogrel in patients with acute myocardial infarction was associated with a 10-fold increase in mortality (0.7% vs 7.5%; P <.0001) and increase in cardiac hospitalizations (14% vs 23%; P = .08) atthe end of 1 year.26
A number of factors may infl uence adherence, one being the complexity of the medication regimen.10,27-30 Complexity of a prescribed medication regimen has been shown to be inversely related to patient adherence.10,29 The complexity consists of 3 major domains: the number of medications prescribed, the complexity of administration, and daily dosing frequency.30 For patients with CVD, who often take multiple medications, including the use of combination products, it can be diffi cult to signifi cantly reduce the number of medications needed for optimal patient outcomes. The complexity of the administrations is not typically an issue in the management of chronic CVD since most medications are taken orally. Subsequently, the simplifi cation of daily dosing frequency may have the most potential to improve drug adherence in patients with CVD.
While it may seem intuitive that a simplifi ed dosing schedule would improve adherence, the literature investigating the relationship between adherence and daily dosing frequency is limited to smaller studies that are fairly old and meta-analyses of these previous studies.16,30,31 The research has suggested that patients are more adherent to drugs with a once-daily (QD) dosing schedule compared with drugs requiring more frequent dosing, but there are concerns about the generalizability of the results. Another major limitation of the current data is that much of the data focus on a single drug or drug class. Additionally, the data are limited to the assessment of adherence of a single therapeutic class, such as only hypertension, dyslipidemia, or diabetes. There have been studies that have compared medication adherence across a variety of different disease states, but these analyses often included disease states that are unrelated, such as epilepsy, hypertension, and osteoporosis. 32,33 Recognizing the scarcity of broad-based multitherapeutic evidence related to adherence and the need to generate relevant data for the patients with CVD, this study attempts to estimate adherence from the broader multi-therapeutic perspective of classes of medications that are commonly used by patients with CVD. The objective of this study is to compare patient adherence between QD and twice-daily (BID) dosing with chronic-use prescription medications commonly used by patients across the spectrum of CVD with a large, recent, commercial database.
Data Source and Data Selection
The study data are from the Thomson Reuters MarketScan Research Databases (Ann Arbor, Michigan). The MarketScan Commercial Claims and Encounters plus the Medicare Supplemental databases are large insurance claims databases with both working age employer-sponsored insurance and patients with Medicare Supplemental Insurance. Pharmacy claims contained quantities of drug dispensed, days supply, and costs.
Data were from July 1, 2006, to December 31, 2008. The first prescription fi ll date, or index date, for 1 or more of the drugs of interest, as described below, occurred between January 1 and December 31, 2007, and prescription data needed to be available for the entire period of time between 6 months prior to and 12 months after the index date. The unit of analysis was drug therapy for 1 year; therefore, patients were permitted to have prescription claims for more than 1 drug in this analysis.
Drugs were selected for inclusion in the study if they were in capsule or tablet form and could be grouped into 1 of the following therapeutic classes: antidiabetic (eg, metformin, thiazolidinediones, sulfonylureas), antihyperlipidemic (eg, statins, fi brates), antiplatelet (eg, clopidogrel, aspirin/dipyridamole, cilostazol), or cardiac agents (eg, ACE inhibitors, antiarrhythmic agents, alpha-beta blockers, calcium channel blockers). For each prescription claim, the quantity of pills per day was calculated. A drug was designated as having either QD or BID dosing if >80% of the claims had a quantity per day of either 1 or 2, respectively.
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