AJMC: Simplifying dosing regimens may improve medication adherence

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Source: AstraZeneca
A once-daily dosing regimen was related to greater adherence versus a twice-daily regimen with prescription medications used by patients with cardiovascular disease (CVD), according to a large analysis in the March issue of the American Journal of Managed Care.

“Despite evidence of significant clinical benefit, for patients with CVD [cardiovascular disease], adherence is often suboptimal,” wrote the study authors. “It has been estimated that 40 percent to 50 percent of patients with CVD may be non-adherent, and this reduction in adherence may be seen at approximately three to six months of therapy. Medication non-adherence is a commonly recognized source of adverse patient outcomes and use of healthcare and associated costs.”

The researchers also noted that the complexity of a prescribed medication regimen consists of three major domains: the number of medications prescribed, the complexity of administration and daily dosing frequency. “While it may seem intuitive that a simplified 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,” they wrote.

Thus, Paul P. Dobesh, PharmD, from the College of Pharmacy at the University of Nebraska Medical Center in Omaha, and colleagues assessed 1.08 million patients (at least age 18 years) with a prescription index date from Jan. 1, 2007, to Dec. 31, 2007, for an antidiabetic, antihyperlipidemic, antiplatelet or cardiac agent with once-daily or twice-daily dosing. The adherence, defined as medication possession ratio (MPR), was the number of days of medication supplied between the first prescription fill date and the subsequent 365 days divided by 365 days.

For the study, the researchers assessed mean MPR and comparisons between dosing frequency groups with a generalized estimating equation. Covariates included age at index date, gender, Charlson comorbidity index, therapeutic class, dosing frequency, as well as the interaction between therapeutic class and dosing frequency group.

Overall, they found the adjusted mean MPR value for once-daily agents was 13.6 percent greater than twice-daily agents (0.66 vs. 0.57). The adjusted mean MPR value for once-daily agents was 2.9 percent, 17.5 percent and 29.4 percent greater than twice-daily agents in the antidiabetic, antihyperlipidemic and antiplatelet therapeutic classes, respectively.  

For cardiac agents, the adjusted mean MPR value was similar between once-daily and twice-daily agents. Carvedilol (Coreg, GlaxoSmithKline) represented approximately 80 percent of the cardiac agents in the twice-daily group. Dobesh and colleagues reported that the adjusted mean MPR for carvedilol phosphate once-daily was 0.73 and 0.65 for carvedilol twice-daily—an 11 percent difference.

This study found a once-daily dosing regimen was related to a 16 percent higher rate of adherence over a twice-daily regimen. “While the study did not compare clinical outcomes related to the adherence difference, it is likely that such an increase would lead to improved clinical outcomes,” wrote the study authors. “Providing patients with access to simplified dosing regimens may be an important factor in maximizing therapeutic success.”

According to the researchers, the current study is the first large-scale effort to validate the often-held assumption that the complexity of a cardiovascular dosing regimen impacts medication adherence, and presented these takeaway points:
  • ­Across the four therapeutic classes studied (antidiabetic, antihyperlipidemic, antiplatelet and cardiac), adherence for once-a-day regimens was 14 percent higher than for twice-daily agents.
  • ­Regardless of dosing regimen, adherence for many patients remains suboptimal.
  • ­Providing patients with access to simplified dosing regimens may be an important factor in maximizing therapeutic success.