September 11, 2013
Fixed-Dose Combination Pill Improves Medication Adherence for CVD Prevention

London—Dispensing a fixed-dose combination medication to lower cardiovascular risks significantly improved medication adherence compared to usual care in a 15-month trial of 2,000 patients with or at high risk of cardiovascular disease (CVD).

The combination pill for blood pressure, cholesterol, and platelet control also led to small improvements in systolic blood pressure and low-density lipoprotein cholesterol, according to the study published recently in the Journal of the American Medical Association.

“The long-term use of cardiovascular disease preventive therapy is low among people with established disease. 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,” according to the article’s background.

The authors suggest that “fixed-dose combination (FDC) therapy may reduce these treatment gaps by reducing cost, complexity, therapeutic inertia, and low adherence.” Their study compared cardiovascular FDCs to usual care over a longer period of time, compared to previous trials that looked at the combination pills in the short term and compared to placebo.

The study, led by researchers from the International Centre for Circulatory Health at Imperial College in London, sought to assess whether FDC delivery of aspirin, statin, and two blood pressure–lowering agents was more effective than usual care in improving long-term therapy adherence, systolic blood pressure, and low-density lipoprotein cholesterol. The randomized trial included 2,004 participants with established CVD or at risk of CVD enrolled from July 2010 to July 2011 in India and Europe, with trial follow-up continuing until July 2012.

Half of the participants were randomly assigned to a combination pill strategy containing one 75-mg aspirin, 40-mg simvastatin, 10-mg lisinopril, and 50-mg atenolol or two 75-mg aspirin, 40-mg simvastatin, 10-mg lisinopril, and 12.5-mg hydrochlorothiazide. The other half received usual care as determined by their physicians, which may have included a variety of medications taken separately.

At baseline, average blood pressure was 137/78 mmHg and low-density lipoprotein cholesterol was 91.5 mg/dL. More than half of the study participants, 61.5%, reported that they used an antiplatelet, statin, and two or more antihypertension medications.

At study’s end, 829, 86.3%, of the 961 remaining participants in the FDC group were continuing with prescribed medications compared with 621, 64.7%, of the remaining 960 in the usual care group—a 21.6% difference in treatment rates. Overall, blood pressure (-2.6 mm Hg) and low-density lipoprotein cholesterol (-4.2 mg/dL) levels showed small but significant reductions in the combination-pill group compared with the usual care group.

The authors note that, in a subgroup of 727 patients with lower adherence at baseline, 77% stuck with the combination pill treatment versus 23% of those receiving usual care. In addition, blood pressure was reduced by 4.9 mmHg, and low-density lipoprotein cholesterol was reduced by 6.7 mg/dL.

No significant differences in serious adverse events or cardiovascular events were noted between the groups, however, according to the authors.

“To the best of our knowledge, this was the first randomized trial to assess the long-term use of an FDC containing antiplatelet, statin, and BP-lowering drugs compared with usual care in patients with CVD,” according to the study’s conclusions. “The results show that access to FDCs in patients with CVD or 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."

Despite the results, an accompanying editorial by J. Michael Gaziano, MD, MPH, of the VA Boston Healthcare System, Brigham and Women’s Hospital and Harvard Medical School, all in Boston, suggests that 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,” Gaziano suggests. “Another way to reduce the number of pills patients are taking is to eliminate those medications for which the benefits are marginal.”

U.S. Pharmacist Social Connect