LOS ANGELES, CA—A fixed dose ‘polypill’ including antiplatelet, statin, and anti-hypertensive drugs improves adherence, blood pressure, and cholesterol in patients with cardiovascular disease, according to a study presented November 5, 2012, at the American Heart Association Scientific Sessions.

For the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) trial, researchers led by Simon A. Thom, MD, of Imperial College, London (London, United Kingdom), randomized 2,004 patients with established cardiovascular disease or at high risk of developing the condition to either a treatment strategy based on the polypill (n = 1,002) or continued usual care (n = 1,002). Patients were enrolled at 28 sites in India and Europe from 2010 to 2011.

There were 2 versions of the polypill used depending on physician preference—both included aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg plus either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Patients in the polypill arm received the study drug free of charge, while patients in the usual care group, which consisted of standard conventional therapies, were subject to local payments or exemptions.

One Pill Solves Several Problems

After a median follow-up of 15 months, patient adherence, systolic blood pressure and LDL cholesterol had all improved in the polypill arm compared with the usual care group (table 1).

Table 1. Effects of Treatment on Adherence, Blood Pressure, and Cholesterol

^aRR for adherence and mean difference for BP and cholesterol.

Adherence favored the polypill in all prespecified subgroups, especially in patients who were not adherent to indicated medications at baseline (P < 0.001). In addition, patients treated with the polypill had lower diastolic BP (72.8 mm Hg vs. 75.2 mm Hg; P < 0.0001), higher creatinine (94.6 mmol vs. 91.9 mmol; P < 0.002), and a higher quality of life based on the EuroQoL 5D Questionnaire (76.1 vs. 73.7; P = 0.002).

Patients in the study and control arms reported roughly the same number of serious adverse events (154 vs. 142) and there were no significant differences by type of event.

Closing the Adherence Gap

“The effect, a 33% increase in adherence over a 15 month interval, was evident in a trial population with an unusually high reported use of indicated medication at the outset,” Dr. Thom said.

After completion of the trial, Dr. Thom noted that patients preferred to continue on the polypill if they had the choice. “There is a universal enthusiasm for it,” he said, noting that recruitment for the trial was the “quickest of any trial I’ve ever been involved in.”

The medical community needs to focus on developing and adopting additional measures to close the adherence gap, he emphasized. “If we can persuade physicians and patients through partnership and understanding to develop a technique of enhancing continued adherence of medication, we would address a great deal of the targets of cardiovascular disease prevention that face us,” Dr. Thom concluded.

Lifestyle Complementary to Polypill

Commenting on the trial, Andrew M. Tonkin, MD, of Monash University (Melbourne, Australia), said that the “free provision [of the polypill] probably favored adherence,” but the decrease in systolic BP, though seemingly small, could translate to “major public health benefits.”

He questioned the appropriate setting for use of the polypill depending on patient demographics, geography, and economic status, but said that UMPIRE “establishes the case for [using the polypill in all] atherosclerotic [cardiovascular disease].”

Further, Dr. Tonkin said that it is “high time that we saw lifestyle modification and the polypill as complementary and not competitive,” noting that both can be impacted by government policies.

The polypill lies at the “other end of the spectrum” from personalized medicine, Dr. Tonkin concluded. “In terms of where we are, I really believe that UMPIRE is headed toward the information that will really inform government strategies.”

Study Details

Baseline characteristics were well balanced between study cohorts, with patients averaging 62 years of age. More than 80% were male and, importantly, 59.7% of patients in the polypill arm were already adherent to the indicated medications.

Source:

Thom SA. UMPIRE trial: Use of a multidrug pill in reducing cardiovascular events. Presented at: American Heart Association Scientific Sessions; November 5, 2012; Los Angeles, CA.