Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.
The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.
The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.
The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.
Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).
The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.
After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.
At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).
The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.
Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).
The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.
The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.
"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.
Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.
Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.
Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.
Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.
The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.