From Prevention When will all this nonsense end?
WHO trial shows acceptability of polypill in a developing county
January 28, 2011
Winston-Salem, NC - A pilot trial of a polypill for primary prevention of cardiovascular disease in Sri Lanka has shown this approach to be practical in a developing country and demonstrated that the polypill is highly acceptable among both patients and doctors .
"This study has fulfilled its purpose; we wanted to check the feasibility of doing a large-scale clinical trial with a polypill in a developing country, and from this perspective we now know that it's feasible," lead author Dr Elsayed Z Soliman (Wake Forest University School of Medicine, Winston-Salem, NC) told heartwire. Soliman and colleagues report their findings, the only such study sponsored by the World Health Organization (WHO), online January 5, 2011 in Trials.
The polypill was as effective as standard treatment in the population studied, but Soliman points out that "standard" treatment in this trial was administered from a tertiary-care center, and so it was "very sophisticated, complicated therapy."
And he says that although feasibility has been demonstrated, there are many questions to resolve before going forward with future, large trials of polypills. First, which patient population should a polypill be aimed at: primary or secondary prevention? What components and what doses should be in the pill? He notes that there is now a question mark over aspirin, at least in the primary-prevention population. And what should it be compared with? The separate components of the pill, placebo, or "standard treatment," and if the latter, how should that be defined? "All of these questions will never be answered by a single trial," he notes.
Polypill deemed acceptable by 90% of patients and >80% of doctors
Soliman et al conducted an open-label, parallel-group, randomized clinical trial that enrolled a total of 216 patients without established cardiovascular disease with an estimated 10-year total CVD risk score >20% from three sites in Sri Lanka. Patients were randomized to a polypill containing 75 mg of aspirin, 20 mg of simvastatin, 10 mg of lisinopril, and 12.5 mg of hydrochlorothiazide (Red Heart pill 2b; Reddy's Laboratories, India) or to standard practice and followed for three months.
Prespecified primary outcomes included reduction in systolic BP, total cholesterol, and estimated 10-year CVD risk. The researchers also assessed the recruitment process and the acceptability of the polypill by physicians and patients.
Of the patients, 203 completed the three-month treatment and returned for their three-month follow-up visit; both the polypill and standard treatment resulted in marked reductions in systolic BP, cholesterol, and 10-year risk of CVD, but there was no significant difference between the groups.
Of the patients who completed the trial, 90% said they would take the polypill "for life" if it were proven to be effective in reducing CVD risk; 86% of doctors supported the use of the polypill for primary prevention and 93% for secondary prevention.
Lessons learned should guide future studies
Soliman and colleagues explain they were unable to estimate the risk-factor reductions on the polypill "because the control group received similar treatment with individual drugs." However, they note that the polypill was "simpler" and achieved comparable risk-factor reductions, "highlighting its potential usefulness in the prevention of CVD."
And they point out that the three tertiary-care hospitals involved in this study "do not reflect the level of medical care provided at primary-care centers and secondary-level hospitals in Sri Lanka. Thus, the findings from the selected trial sites cannot be generalized to other levels of care.
"Further studies assessing the polypill in developing countries should take into consideration the study design lessons and challenges that we encountered," they conclude.
Other polypill trials are ongoing, including the TIPS 2 study and a collaborative effort called Single Pill to Avert Cardiovascular Events (SPACE), which includes the Use of a Multidrug Pill in Reducing Cardiovascular Events (UMPIRE), the Kanyini Guidelines Adherence with the Polypill (Kanyini GAP) and Improving Adherence Using Combination Therapy (IMPACT) trials.
UPDATE: Sept 8, 2014 - An FDA advisory committee looks at a new cardiovascular polypill about which FDA staff expressed serious reservations http://1.usa.gov/1CNj7AM