Polypills may improve adherence in CVD patients

Less may be more when it comes to improving medication adherence in patients with cardiovascular disease. In the Use of a Multidrug Pill in Reducing Cardiovascular Events (UMPIRE) trial, patients were more likely to continue their drug regimens on a long-term basis if they used fixed-dose combinations (FDCs). These “polypills” also improved systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C).

The researchers, led by Simon Thom, MB, BS, MD, of Imperial College London in the U.K., undertook the UMPIRE trial in response to a request by the European Commission for research evaluating combination medications in the treatment of chronic disease. They published the results in the Sept. 4 issue of JAMA.

UMPIRE included more than 2,000 adults from England, Ireland, the Netherlands and India considered to be at high risk for CVD.  They were randomly assigned to receive either care at the discretion of their physician or one of two FDCs daily. One FDC contained aspirin, simvastatin, lisinopril and atenolol; the other contained aspirin, simvastatin, lisinopril and hydrochlorothiazide. Patients were followed for an average of 15 months.

At the end of the trial, 86.3 percent of the patients in the FDC group continued to take their medications compared with 64.7 percent of patients in the doctor’s care group.

In addition, the FDCs modestly lowered SBP and LDL-C . In the experimental group, SBP decreased by 2.6 mm Hg and LDL-C decreased by 4.2 mg/dL.

Among the subgroups, there were larger benefits in patients who were less adherent and those at higher risk for CVD at the start of the study. Their SBP and LDL-C were also lower than the overall group.

The reasons for better medication adherence in some patients and not in others are complex, but the authors hypothesize that using a polypill approach may offer some considerable advantages. “These encompass ease of prescription, overcoming physician inertia, patient acceptability, packaged delivery and ease of taking,” they wrote.

One important limitation of their study they noted, however, was that patients in the FDC group received their medications for free throughout the study while the usual care group were left to obtain their medications on their own.

Despite this and other limitations, their findings, they added, could someday improve access to critical cardiovascular medications and meet CVD prevention goals in the U.S., Europe and India. The effects could also have a more global impact and “contribute importantly to World Health Organization goals for noncommunicable disease control.”

J. Michael Gaziano, MD, MPH, of Brigham and Women’s Hospital in Boston expanded on the global health prospects of the polypill in an accompanying editorial.

The UMPIRE trial yielded promising findings, but “it would be useful to conduct trials in patients who are less adherent to their medications, as well as trials testing whether a combination pill is useful in lower-income countries where costs and systems of delivering preventive medications to appropriate patients are less developed. It is in this setting that a polypill may have the greatest benefit.”

And while the notion of combination medications seems feasible and promising at the outset, there are a number of challenges to making it a widely used treatment option.

Among them, he noted, are the possibilities that medications may lose stability when combined and they may not interact well with each other. There are also the challenges of producing the drug in a way that is economically feasible.

“Although the potential remains for use of various CVD polypills in certain settings, the precise advantage of this strategy remains largely unproven,” he concluded.