Patients with or at high risk for cardiovascular disease who took a pill that combined aspirin, a statin, and 2 antihypertensives had significantly higher adherence levels than those who received usual care.
After more than a decade of speculation on the possibility of a single pill that combines multiple medications to prevent and treat cardiovascular disease, a European study provides evidence that such a “polypill” may markedly improve adherence and modestly improve blood pressure and cholesterol control in high-risk patients.
, published in the September 4, 2013, issue of the Journal of the American Medical Association
, analyzed the effect of a fixed-dose combination pill on long-term adherence, systolic blood pressure, and low-density lipoprotein cholesterol (LDL). A total of 2004 patients from England, Ireland, the Netherlands, and India who either had cardiovascular disease or were at high risk for cardiovascular disease were randomly assigned to continue with regular care or to receive a combination pill between July 2010 and July 2011. A trial physician determined whether participants in the combination pill group would receive version 1 (75 mg of aspirin, 40 mg of simvastatin, 10 mg of lisinopril, and 50 mg of atenolol) or version 2 (75 mg of aspirin, 40 mg of simvastatin, 10 mg of lisinopril, and 12.5 mg of hydrochlorothiazide).
Follow-up ranged from 1 to 2 years, and patients visited clinics or participated in telephone interviews at 1 month, 6 months, and 18 months. Blood pressure and fasting lipid levels were measured at baseline, 12 months, and at the end of the study in July 2012. Patients self-reported adherence levels by specifying the number of days they took their medication during the week preceding a clinic visit or phone call.
After 1 month, 97.3% of patients in the combination pill group were adherent, compared with 68.3% of regular care patients. At the end of the study, 86.3% of the combination pill patients remained adherent, compared with just 64.7% of regular care patients. Differences in blood pressure and cholesterol between the two groups were not as marked, but levels for patients in the combination group were still significantly lower than for control patients. On average, systolic blood pressure in patients taking combination pills was 2.6 mm Hg lower and LDL cholesterol was 4.2 mg/dL lower than in those receiving regular care.
The results also indicated no significant difference in serious adverse events between the 2 groups. (Patients in the combination pill group experienced 50 cardiovascular events compared with 35 in the usual care group, but this difference was not statistically significant.)
The authors conclude that fixed-dose combination pills may be a viable solution to improving adherence and cardiovascular health among patients at risk for cardiovascular disease. In an accompanying editorial, however, J. Michael Gaziano, MD, MPH, writes that more research should be conducted among the populations that might benefit the most from the polypill.
“[I]t would be useful to conduct trials in patients who are less adherent to their medications, as well as trials testing whether a combination pill is useful in lower-income countries where costs and systems of delivering preventive medications to appropriate patients are less developed,” he writes.
Until more research confirms the benefits of combination pills, Dr. Gaziano suggests that physicians take an inventory of the medications their cardiovascular patients are taking and remove any that may be unnecessary.