Prescription consolidation and fewer pharmacies filling prescriptions were the two most important factors leading to medication adherence, according to a study published online Jan. 10 in the Archives of Internal Medicine.

“In the design of this study, we were attempting to assess the difficulties that patients have in filling their prescriptions, and their effects on subsequent rates of adherence,” the study’s lead author Niteesh K. Choudhry, MD, PhD, from the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women's Hospital in Boston, told Cardiovascular Business News.

The study population comprised 1.83 million individuals prescribed a statin and 1.48 million patients prescribed an ACE inhibitor/ARB between June 1, 2006, and May 30, 2007. The researchers estimated complexity by measuring the number of medications, prescribers, pharmacies, pharmacy visits and refill consolidation (a measure of the number of visits per fill) during the three months from the first prescription. The number of daily doses also was measured in ACE inhibitor/ARB users. After this period, adherence was evaluated over the subsequent year.

“During a three-month period, we evaluated the patients’ use of other healthcare services, such as: How many times did they go to pick up medications at the pharmacy? How many different medications did they pick up? How many different prescribers were there?” Choudhry explained. “By these markers, we determined the complexity of a patient’s medication filling patterns. Over the following year, we assessed their adherence.”

To gather their data, the researchers used prescription claims data from CVS Caremark, based in Woonsocket, R.I., a pharmacy benefit manager with more than 50 million beneficiaries throughout the U.S.

During the three-month complexity assessment period, the statin cohort (mean age of 63 years; 49 percent male) filled an average of 11.4 prescriptions per person for 6.3 different medications, had prescriptions written by two prescribers and made five visits to the pharmacy, reported the researchers, who noted that the results for ACE inhibitor/ARB users were similar.

“More striking,” the authors wrote, “during this same [three-month] timeframe, 10 percent of patients filled prescriptions for 23 or more medications, 12 or more unique medications and 11 or more different drug classes, had prescriptions written by four or more prescribers, filled them at two or more pharmacies and made 11 or more visits to the pharmacy.”

Choudhry and colleagues concluded that “greater prescribing and filling complexity was associated with lower levels of adherence.” In adjusted models, patients with the least refill consolidation had adherence rates that were 8 percent lower over the subsequent year than patients with the greatest refill consolidation.

Choudhry noted that the results between the statin and the ACE inhibitor/ARB cohorts were “amazingly similar.” For example, in the adjusted models, the patients who had fully consolidated their prescriptions in the statin arm were 8.4 percent more adherent than those who had not at all, whereas in the ACE inhibitor/ARB cohort, these patients who had fully consolidated their prescriptions were 8.1 percent more likely to be adherent. “All of our markers were nearly as identical,” he explained.

The two most important determiners of medication adherence were refill consolidation and the number of pharmacies at which the patients are filling their prescriptions, according to the researchers. “For example, patients were 2 percent less adherent to their medications for every additional pharmacy at which the patients filled their prescriptions,” Choudhry said.

The researchers also tried to assess if economics played into adherence. “Based on patients’ zip codes, we assessed the average income of the residents in that area,” he said. “We found that patients in more affluent areas were 1 to 2 percent more adherent than patients in less affluent areas, which is consistent with previously published data.” Of note, the majority of the study participants received healthcare insurance from their employers, but Medicare beneficiaries also were included.

“Chronic disease is extremely difficult to manage. Of late, we are advocating more and more medications to treat multiple comorbidities, such as diabetes, hypertension and high cholesterol, and we provide patients numerous medications to treat symptoms and reduce their risk of complications,” Choudhry said. “Our findings amplify the sheer volume of medications that patients are typically filling. As physicians, we know what medications to prescribe, but we rarely think about the next step in the cascade, especially if our patients are receiving prescriptions from various providers.

“We found that aspects of therapeutic complexity can undermine the goals of chronic disease management,” he concluded. “Individual physicians and our healthcare system as a whole need to consider these factors when attempting to address medication non-adherence.”