A Randomized Trial of the “Polypill” for Cardiovascular Risk Modification

Long-term use of recommended cardiovascular (CV) risk modifying medications is low among patients at high-risk for CV events.  Fixed-dose drug combination (FDC) therapy may reduce treatment gaps by lowering non-adherence, cost, complexity and therapeutic inertia. However, FDC may also reduce tailoring of individual medications and thereby lead to suboptimal risk control. The UMPIRE (Use of Multidrug Pill in Reducing Cardiovascular Events) randomized, open-label trial compared FDC versus usual care among individuals with high risk (>15% risk over 5 years) for CV disease and clear indications for aspirin, statin, and blood pressure lowering medications. A total of 2004 participants were randomized to FDC or usual care. Primary outcomes included change in self-reported adherence to all medications and changes in LDL and systolic blood pressure (SBP) from baseline.  Overall, 88% of participants had established CAD. Median follow-up duration was 15 months. Patients treated with FDC has significantly improved adherence (RR 1.13, 95% CI 1.08 – 1.18) and change in SBP (-2.6 mm Hg, 95% CI -4.0 to -1.1 mmHg) and LDL (-4.2mg/dL, 95% CI -6.6 to -1.9 mg/dL). There were no significant differences in adverse events between the two groups.

Conclusions:

Among patients at high-risk for CV events, use of FDC led to improved medication adherence and measures of CV risk compared to usual care. However, given that FDC was provided free of charge and usual care was not, it is uncertain how much of this effect simply reflects the cost of care. Future studies powered for CV events and accounting for cost differentials in therapy may further inform the role of FDC strategies for CV risk reduction.

  •  Thom S, Poulter N, Field J, et al. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA : the journal of the American Medical Association. Sep 4 2013;310(9):918-929.