In a randomized trial that included about 2,000 patients with or at high risk of cardiovascular disease, use of a fixed-dose combination medication for blood pressure, cholesterol and platelet control resulted in significantly improved medication adherence after 15 months and small improvements in systolic blood pressure and low-density lipoprotein cholesterol when compared with usual care.
The long-term use of cardiovascular disease preventive therapy is low among people with established disease, researchers wrote in the Sept. 4 issue of the Journal of the American Medical Association. This shortfall is greatest in low- and middle-income countries, but even in high-income countries treatment coverage in the community is only about 50% in those with coronary disease and 35% in those with stroke. People who are at similar risk but have not reached the clinical threshold of experiencing a CVD event are even less likely to be adequately treated.
Fixed-dose combination therapy may reduce these treatment gaps by reducing cost, complexity, therapeutic inertia and low adherence. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.
Simon Thom, MB, BS, MD, of the International Centre for Circulatory Health, Imperial College London, and colleagues conducted a study to assess whether fixed-dose combination delivery of aspirin, statin and two blood pressure-lowering agents versus usual care improves long-term adherence to indicated therapy and two major CVD risk factors, systolic blood pressure and low-density lipoprotein cholesterol.
The randomized trial included 2,004 participants with established CVD or at risk of CVD who were enrolled in India and Europe between July 2010 and July 2011. The trial follow-up concluded in July 2012. Participants were randomly assigned to a fixed-dose combination-based strategy containing either 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril and 50 mg atenolol, or 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide; or to usual care.
At baseline, average BP was 137/78 mm Hg, LDL-C was 91.5 mg/d, and 1,233 (61.5%) of 2,004 participants reported use of antiplatelet, statin and two or more BP-lowering medications. The median duration of follow-up was 15 months for both groups.
At the end of the study, 829 (86.3%) of 961 participants in the fixed-dose combination group were continuing with indicated medications, compared with 621 (64.7%) of 960 in the usual care group. Systolic blood pressure (-2.6 mm Hg) and LDL-C (-4.2 mg/dL) levels were modestly but statistically significantly lower in the fixed-dose combination group compared with the usual care group at the end of the study.
The authors noted that in a subgroup of 727 participants with lower adherence at baseline, adherence was 77% for those receiving fixed-dose combination therapy and 23% for those receiving usual care. Those in the subgroup who received fixed-dose combination therapy had a reduction of 4.9 mm Hg in systolic blood pressure and 6.7 mg/dL in LDL-C.
There were no significant differences in serious adverse events or cardiovascular events between the groups, the authors wrote.
To the best of our knowledge, this was the first randomized trial to assess the long-term use of an FDC containing antiplatelet, stain and BP-lowering drugs compared with usual care in patients with CVD, the authors concluded. The results show that access to FDCs in patients with CVD of similarly high risk improved adherence, BP and cholesterol levels. The reductions in BP and cholesterol level were small overall in this comparatively well-treated population but were larger in the subgroup not receiving all recommended treatments at baseline.
In an accompanying editorial, J. Michael Gaziano, MD, MPH, of the VA Boston Healthcare System, Brigham and Womens Hospital and Harvard Medical School in Boston, and associate editor of JAMA, wrote: Although the potential remains for use of various CVD polypills in certain settings, the precise advantage of this strategy remains largely unproven.
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. Another way to reduce the number of pills patients are taking is to eliminate those medications for which the benefits are marginal.