Fixed-dose combination pills may improve adherence, persistence in adults with hypertension

Prescribing fixed-dose combination pills to patients with hypertension may help improve their adherence and persistence to their medications, as well as encourage them to refill their prescription, according to a claims database analysis.

After adjusting for multiple variables, patients who initiated with fixed-dose combination oral therapy were 9 percent more likely to be persistent and 13 percent more likely to be adherent compared with patients who began with a single anti-hypertensive therapy. The fixed-dose combination group was also more likely to refill at least one anti-hypertensive medication.

Lead researcher Julie C. Lauffenburger, PharmD, PhD, of Harvard University and Brigham and Women’s Hospital in Boston, and colleagues published their results online in the Journal of General Internal Medicine on Jan. 3.

“Fixed-dose combination pills appear to enhance adherence and persistence to anti-hypertensive medications among commercially insured patients starting treatment compared with single therapy," Lauffenburger said in a news release. For patients beginning anti-hypertensive treatment, clinicians may therefore want to consider starting patients on a fixed-dose combination pill rather than a single therapy.”

The researchers evaluated claims from a large health insurance company and identified 484,493 patients who initiated oral hypertension treatment from Jan. 1, 2009 to Dec. 31, 2012. They included all oral anti-hypertensive medications except for sotalol, furosemide and bumetanide.

The patients were at least 18 years old and continuously enrolled in the insurance plan for at least 180 days before and 365 days after their index date. They were excluded if they had filled any anti-hypertensive medication before the index date.

Patients were considered to be persistent if they took any anti-hypertensive medication 12 months after starting treatment. They were considered to be adherent if they took at least one anti-hypertensive medication in the 12 months after starting treatment and also refilled at least one anti-hypertensive medication. The researchers defined full adherence as having at least 80 percent of potential days covered with medications.

The mean age was 47.2 years old, while 51.8 percent of patients were women and 46.9 percent were diagnosed with hypertension in the prior 180 days.

Of the patients, 78,958 patients initiated fixed-dose combinations, 383,269 initiated a single therapy and 22,266 initiated multi-pill combinations. The researchers defined a fixed-dose combination as a single pill containing multiple medications, a multi-pill combination as two or more anti-hypertensive tablets or capsules filled on the index date and single therapy as only one medication filled on the index date.

Lisinopril/hydrochlorothiazide was the most frequently initiated fixed-dose combination (38.4 percent), while lisinopril (26.5 percent), hydrochlorothiazide (12.3 percent) and amlodipine (13.3 percent) were the most frequently initiated single therapies.

The researchers mentioned they focused on patients initiating fixed-dose combinations and single therapies because they were more comparable in terms of baseline characteristics and medications initiated.

Patients in the fixed-dose combination group were more likely to be older and female and have chronic obstructive pulmonary disorder (COPD), asthma or concomitant liver disease. The single therapy group was more likely to have coronary artery disease or congestive heart failure.

The persistence rates were 51.2 percent for the fixed-dose combination group and 43.0 percent for the single therapy group, while the adherence rates were 51.3 percent and 42.1 percent, respectively. In addition, 84.4 percent of patients in the fixed-dose combination group and 76.8 percent of patients in the single therapy group refilled at least one anti-hypertensive medication.

Multivariable regression analyses found that the following variables were associated with persistence and adherence in patients initiating fixed-dose combinations compared with single therapies: increased age, dementia, congestive heart failure, coronary artery disease, COPD/asthma, diabetes, kidney disease, liver disease and previous stroke. Meanwhile, women and people with a previous hospitalization were less likely to be adherent and persistent.

The study had a few limitations, according to the researchers, including that it only evaluated commercially insured adults or those with Medicare Advantage. Thus, the results might not be generalizable to all U.S. adults. They also did not have blood pressure values, hypotension or patients’ other clinical information at baseline or during the follow-up period, so the patients might have received medications for indications other than for hypertension. In addition, the study did not assess clinical outcomes.