LONDON, UK — Taking a single pill with a fixed-dose combination of an aspirin, a statin, and two antihypertensives improved adherence to medication and slightly improved systolic blood pressure and LDL-cholesterol levels compared with usual care in a 15-month study of patients with or at high risk of CVD.
These findings, from the Use of a Multidrug Pill in Reducing Cardiovascular Events (UMPIRE) study, were published September 4, 2013 in the Journal of the American Medical Association. Part of the study results had been presented at the American Heart Association 2012 Scientific Sessions, as previously reported by heartwire .
"This is the first trial to our knowledge evaluating [fixed-dose-combination] FDC-based care over a prolonged interval in participants with established CVD or at similarly high levels of risk, among whom more than 40% of all cardiovascular events occur," Dr Simon Thom (Imperial College London, UK) and colleagues write. "These data suggest that FDCs could play a role in increasing uptake of statins, aspirin, and combination blood-pressure–lowering drugs in patients with CVD not currently receiving such treatment."
Did this study hit a home run for this controversial strategy? Not necessarily. According to an accompanying editorial by Dr J Michael Gaziano (Brigham and Women’s Hospital, Boston, MA), this research was done in a select, high-risk population, and "although the potential remains for use of various polypills in certain settings, the precise advantage of this strategy remains largely unproven ".
UMPIRE Designed to Test Pill Suited for Poor Countries
According to the researchers, UMPIRE was designed to meet an appeal from the European Commission in 2009 for research to test "a single daily . . . fixed-dose-combination pill [that is] low-cost and suitable for production and widespread use in resource-poor countries."
UMPIRE randomized 2004 patients with known or at high risk for CVD living in India, England, Ireland, and the Netherlands. Half of the patients received usual care and half received a daily tablet containing 75 mg of aspirin, 40 mg of simvastatin, 10 mg of lisinopril, and either 12.5 mg of hydrochlorothiazide or 50 mg of atenolol (depending on physician preference).
The primary outcome was self-reported adherence to the medication and change in systolic blood pressure and LDL cholesterol from baseline.
The patients had a mean age of 62, and 82% were men. At baseline, their mean blood pressure was 137/78 mm Hg and mean LDL cholesterol was 91.5 mg. Most were receiving a statin (87.8%), an antiplatelet drug (91.4%), two or more blood pressure-lowering drugs (68.4%), or all of these indicated drugs (61.5%).
After a mean follow-up of 15 months, compared with patients in the usual-care group, those in the polypill group had improved adherence (86% vs 65%) and a small but statistically significant greater improvement in systolic blood pressure (-2.6 mm Hg) and in LDL cholesterol (-4.2 mg/dL).
Benefits were larger in the subgroup of 727 patients with low adherence to begin with. In this group, randomization to a polypill resulted in a threefold increase in adherence: 77% vs 23%.
There were no significant differences in serious adverse events or cardiovascular events between the two groups.
"Assess Multiple Pills, Eliminate Marginal Ones"
The current study shed light on using a polypill in high-risk patients who were already taking multiple pills and were generally compliant in taking their medications, Gaziano writes. However, it would be useful to test this pill in different settings: patients who were less compliant to taking medications or patients in low-income countries with less access to healthcare. More research is also needed to examine risks and benefits in older patients taking a polypill as a preventive strategy.
In the meantime, physicians should verify whether some patients are taking too many pills. "Until additional rigorous data are available that demonstrate that the polypill improves clinical CVD outcomes, it may be more important to carefully assess the multiple medications many patients currently are prescribed, often by several physicians," he writes. "Another way to reduce the number of pills patients are taking is to eliminate those medications for which the benefits are marginal."
Thom received reimbursement from Dr Reddy’s Laboratories for travel costs related to visiting India for the UMPIRE trial start-up meetings and again for trial-site visits. Disclosures for the coauthors are listed in the paper. Gaziano reports having no conflicts of interest.
Heartwire from Medscape © 2013 Medscape, LLC
Cite this: Polypill May Benefit Certain Patients With CVD: UMPIRE - Medscape - Sep 06, 2013.