A Polypill Strategy to Improve Adherence: Results From FOCUS (Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention) Project

Study Questions:

In the post-myocardial infarction (MI) setting, what are predictors of medication adherence, and what is the effect of a fixed-dose combination (or polypill), compared to drugs administered separately, in this population?

Methods:

There were two phases to the FOCUS study. Phase 1 was a cross-sectional analysis to characterize factors associated with patients’ adherence to treatment in five different countries (Argentina, Brazil, Italy, Paraguay, and Spain). Although the inclusion criteria were initially limited to patients with an acute MI in the preceding 2 years, this was amended to allow for inclusion of patients with any history of acute MI. In phase 1, the authors determined adherence to guideline-based medical therapy (aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and statin) based on responses to the self-reported Morisky-Green medication adherence questionnaire (MAQ) and identified factors contributing to inadequate adherence to treatment. Phase 2 was a randomized, open label, active-controlled, two-group parallel trial of patients who participated in Phase 1. Patients were randomized to the polypill (aspirin 100 mg, simvastatin 40 mg, and ramipril at three different doses of 2.5, 5, and 10 mg), or the three medications given separately. Both polypill and control groups received medications at no cost and had an identical visit plan. In Phase 2, adherence was determined through responses on the self-reported MAQ and pill count. The primary outcome was percentage of patients taking medication adequately at 9 months in each arm, assessed by attendance at the final 9-month follow-up visit and the MAQ and pill counts. Risk factor control (blood pressure and low-density lipoprotein cholesterol levels at 1 and 9 months) was also assessed in each arm.

Results:

A total of 2,118 patients were enrolled in Phase 1; mean time from index MI was 3.5 years. Average baseline adherence (based on a score of >20 on the MAQ) was 45.5%. The following were independent predictors of inadequate adherence: younger age (younger than 50 years old), depression, and complex treatment regimen (defined as administration other than oral). In Phase 2, 695 patients were randomized. In the intention-to-treat analysis, 41% and 50.1% of patients in the usual care and polypill groups, respectively, were taking medication adequately at 9 months (p = 0.019). There were no significant differences in blood pressure and cholesterol levels between control and polypill groups. There were no significant differences in adverse events.

Conclusions:

Younger age, depression, and a complex drug treatment plan are associated with lower medication adherence post-MI. The use of a polypill, compared to drugs given separately, is associated with significantly improved adherence at 9 months.

Perspective:

This is an important study that provides valuable insight into medication adherence post-MI. The authors identified depression as the single most important factor impacting medication adherence, corroborating other reports from the literature. Targeted strategies to improve adherence may be well justified in this population. Although access to a polypill improved adherence significantly by 22% in this study, the results from this study are sobering. Only half of patients in the polypill group (in the intention-to-treat analysis) were adherent to medications at 9-month follow-up; medications were given for free and patients had frequent follow-up. Under the same circumstances (medications given for free), only 41% of patients were adherent in the control group. While a polypill strategy may be a useful strategy to improve adherence (particularly in resource-limited settings), such data (and that from others which may even suggest lower adherence at a mean time since MI of 3.5 years, as in FOCUS) is certainly a call to action to address the issue of nonadherence.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Statins

Keywords: Depression, Myocardial Infarction, Blood Pressure, Simvastatin, Ramipril, Italy, Lipoproteins, LDL, Medication Adherence, Cholesterol, Drug Combinations, Brazil, Intention to Treat Analysis, Spain, Questionnaires, Patient Compliance, ESC Congress


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