The polypill, a fixed-dose, once-daily gelcap combining several medications for cardiovascular (CV) disease prevention, offers a pragmatic strategy to simplify drug regimens and improve adherence. Yet despite its potential benefits and low cost of less than a dollar a day, the polypill has been a tough sell. When an FDA advisory panel debated the all-in-one pill in 2014, discussion was stymied by concerns about the inability to individually tailor drug components.
Pushing forward, a team of Vanderbilt University Medical Center researchers conducted a study in Mobile, Alabama to test polypill efficacy. Daniel Muñoz, M.D., William J. Blot, Ph.D., Thomas J. Wang M.D., and their team found that, when compared with usual care, polypill use translated to a 25 percent reduction in CV event risk and no significant adverse events. They published their results in the New England Journal of Medicine.
“The advantages of the polypill include its simplicity, convenience and ease in understanding its benefits,” first author Muñoz said. With CV medication compliance around 50 percent, these factors loom large. “The focus is really on population risk. The polypill’s low-cost and minimal side effects make it an example of a broadly-applicable, population-based strategy for CV risk reduction.”
A Real World Trial
The polypill in the study is a fixed-dose combination of four generic drugs: one statin and three antihypertensives (atorvastatin 10 mg, amlodipine 2.5 mg, losartan 25 mg, and hydrochlorothiazide 12.5 mg). “We chose this combination because they are road-tested, have minimal to modest side effect profiles, are easy to assemble, and fit in a gel capsule of reasonable size,” Muñoz said.
To raise awareness of the study and polypill, the researchers first conducted information sessions with community-based providers in Mobile. The providers helped the researchers recruit an underserved population of patients at risk of CV disease.
“We wanted to know what works and what doesn’t for at-risk patients who have not been traditionally included in clinical trials,” Muñoz said. “That was a really important part of the research for us – to make the results meaningful.”
“We wanted to know what works and what doesn’t for at-risk patients who have not been traditionally included in clinical trials.”
Together with community providers, the team recruited 303 adults without CV disease for the study, with almost half having stage 2 or higher hypertension and about half taking an antihypertensive medication. Ninety-six percent were African American, and 75 percent had annual incomes under $15,000. Participants were randomized into either a polypill or a usual care group.
In obtaining buy-in from community providers, the researchers emphasized that they were not out to dictate care. “This was a real-world test. Front-line clinicians were free to make therapeutic adjustments as they saw fit,” Muñoz said.
At baseline, blood pressure readings averaged 140/83mm Hg, and LDL, 113 mg/dl. At the end of 12 months, with polypill adherence at 86 percent, mean systolic blood pressure dropped a net 7 mm Hg compared to the usual care group, and LDL levels decreased a net 11 mg/dl. “Sustaining these improvements would be expected to lower CV risk over the next ten years by about 25 percent, an unquestionably meaningful reduction.” Muñoz said.
Small Nudge Toward Big Steps
This research was preceded by large overseas studies, but despite its success abroad, the polypill has yet to gain traction in the U.S. Muñoz says one impediment is the disincentive for private industry to produce a low-cost generic pill, suggesting creative public-private partnerships focused on public health would likely be required for broad-scale production and implementation.
Muñoz argues that the polypill, while not precision medicine, is an invaluable tool that could be used in conjunction with individualized care. “There are the clear virtues of precision medicine, and there are the realities of population medicine,” he said. “What the polypill may do, particularly for vulnerable populations, is give them a running start toward risk reduction.”
“What the polypill may do… is give them a running start toward risk reduction.”