A team of researchers in Iran, the U.S. and the U.K. may have cracked the code of the elusive polypill, they reported after finding their four-drug concoction effectively reduced adverse CV events in nearly 3,500 patients in the PolyIran study.
It’s been around a decade and a half since the so-called polypill was first proposed as a solution for primary and secondary prevention of CVD, Gholamreza Roshandel, PhD, and co-authors wrote in the August 24 issue of The Lancet, and since then scientists have spent years tackling different formulas of the combo drug. But even successful studies have failed to prove the long-term effects of a polypill.
“These formulations are not yet widely available to clinicians and patients,” Roshandel, of Tehran University of Medical Sciences in Tehran, Iran, and colleagues wrote. “Long-term effects of the polypill on fatal and nonfatal hard endpoints (such as mortality or cardiovascular events) are less established, particularly in primary prevention settings.”
For their study, Roshandel et al. enrolled 6,838 individuals from the PolyIran study, a pragmatic, cluster-randomized trial nested within the larger Golestan Cohort Study in Iran. Participants were randomized 1:1 to a regimen of non-pharmacological preventive interventions alone or the same regimen with an added once-daily polypill. Randomization was stratified by three Iranian districts: Gonbad, Aq-Qala and Kalaleh.
The minimal care group—those randomized to treatment without the polypill—were encouraged with literature about healthy lifestyles, low-salt, -fat and -sugar diets, exercise, weight control and abstinence from smoking and opium. Packages of these educational tools were delivered to patients by the PolyIran field visit team at three and six months, then every six months thereafter.
Participants randomized to prevention with the polypill were first treated with the team’s primary formula—a mixture of 12.5 mg of hydrochlorothiazide, 81 mg of aspirin, 20 mg of atorvastatin and 5 mg of enalapril. Those who developed a cough during follow-up were switched to an alternate formula that subbed 40 mgs of valsartan for the enalapril.
People in the study were followed for 60 months, and during that period 8.8% of the 3,417 individuals in the minimal care group and 5.9% of those in the polypill group experienced a major adverse cardiovascular event (MACE), defined as ACS, fatal MI, sudden death, heart failure, coronary artery revascularization procedures or stroke. Average adherence to the polypill was 80.5% in the treatment group.
Roshandel and his colleagues reported no statistically significant relationship with the presence or absence of pre-existing CVD in patients, but patients who adhered most closely to their polypill regimen saw a 57% reduced risk of MACE compared to the minimal care cohort.
The authors said the frequency of adverse events seemed relatively similar between the two study groups, with 10 and 11 intracranial hemorrhages reported in the polypill group and minimal care group over five years, respectively. There were also 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group.
In a related editorial, Anushka A. Patel and Mark D. Huffman, both of the University of New South Wales in Sydney, called Roshandel et al.’s work “a monumental effort by a dedicated research team to understand the potential value of the polypill.”
“Despite some limitations, this study makes a major contribution to the evidence base for polypills in the prevention of cardiovascular disease globally,” they wrote, noting the findings could be particularly important for low- to middle-income countries where major treatment gaps exist.
“The widespread availability of low-cost polypills, with the inclusion of aspirin for people with established cardiovascular disease, would probably facilitate global goals to provide effective and efficient access to essential medicines to reduce cardiovascular disease morbidity and mortality, whether through initiation, step-up or even substitution of individual medicines.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.