A polypill strategy to improve adherence: results from FOCUS (Fixed-dose Combination Drug for Secondary Cardiovascular Prevention) Project

BACKGROUND Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (AMI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of an FDC strategy on adherence in post-MI patients. OBJECTIVES The cross-sectional FOCUS study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an AMI. Additionally, 695 patients from Phase 1 were randomized into a controlled trial (Phase 2) to test the effect of a polypill (containing aspirin 100 mg, simvastatin 40 mg and ramipril 2.5, 5, or 10 mg) compared to the 3 drugs given separately on adherence, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C), as well as safety and tolerability over a period of 9 months of follow-up. METHODS In Phase 1, a 5-country cohort of 2,118 patients was analyzed. Patients were randomized to either the polypill or 3 drugs separately for Phase 2. Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire (MAQ) and pill count (patients had to meet both criteria for adherence at the in-person visit to be considered adherent). RESULTS In Phase 1, overall CV medication adherence defined as a MAQ score of 20 was 45.5%. In a multivariable regression model, the risk of being non-adherent (MAQ <20) was associated with younger age, depression, being on a complex medication regimen, poorer health insurance coverage, and a lower level of social support, with consistent findings across countries. In Phase 2, the polypill group showed improved adherence compared to the group receiving separate medications after 9 months follow-up: 50.8% vs 41% (p=0.019; intention-to-treat population) and 65.7% vs 55.7% (p=0.012; per protocol population) when using the primary endpoint, attending the final visit with MAQ=20 and high pill count (80-110%) combined, to assess adherence. Adherence also was higher in the FDC group when measured by MAQ alone (68% vs. 59%, p=0.049). No treatment difference was found at follow-up in mean SBP (129.6 vs 128.6 mmHg), mean LDL-C levels (89.9 vs 91.7 mg/dL), serious adverse events (23 vs 21), or death (1, 0.2% in each group). CONCLUSIONS For secondary prevention following AMI, younger age, depression, and a complex drug treatment plan are associated with lower medication adherence. Meanwhile, adherence is increased in patients with higher insurance coverage levels and social support. Compared with the 3 drugs given separately, the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an AMI. CLINICAL TRIAL INFO NCT01321255.