In this study, we tested an innovative intervention designed to enhance medication adherence. We demonstrated that patients in either of the intervention groups had better medication adherence and a longer event-free survival compared to patients in the control group who received usual care. The estimated medical costs for HF for 2010 are $39.2 billion and are continuing to rise.2
Medication nonadherence resulting in HF exacerbation and subsequent hospital readmission is the most common cause of high health care costs,8, 10, 45
demonstrating how important it is to discover effective interventions to improve adherence.7–11
Our study needs to be considered in light of the findings from similar studies. To date, there have been seven investigations testing the impact of interventions designed to improve medication adherence on adherence and outcomes in patients with HF.5, 26, 27, 46–49
In all studies,5, 26, 27, 46–49
adherence rates improved in the intervention compared to control group, but outcomes were improved in only four.5, 26, 27, 48
In the other three studies,46, 47, 49
no change in hospitalization or mortality was noted between the intervention and usual care groups. Potential reasons for failure to demonstrate a difference in outcomes, despite an increase in adherence, include: (1) short follow-up period46, 49
and 2) use of self-report measure, which is subject to reporting bias.47
Among the four studies in which outcomes were better in the intervention group, in only one was the MEMS used to assess medication adherence. The intervention lasted nine months, and involved an interdisciplinary team.27
The effects of the intervention were evident only during the intervention period. The intensity of the intervention and the limited effectiveness suggested that the intervention would not be sustainable in usual practice settings. The remaining three studies in this group were limited by the use of self-report to measure adherence.5, 26, 48
Self-report is subject to recall bias and social desirability.
In our study, the mean medication adherence of patients in the control group was 94.5% at baseline; however, the rate dropped to 90.7% at 2 months and dropped even more to 84.2% at 9 months. The finding was consistent with the previous study, medication adherence rate decreases as time progresses.22, 23
To our knowledge, this is the first study to explore the natural pattern of medication adherence over 9 months in patients with HF. It is important to note that two thirds of patients in the control group were adherent using the cutpoint of 88% at baseline. However, the number of adherent patients dropped dramatically in the control group. The number of adherent patients was maintained over the 9 months in the intervention groups. Therefore, even patients who were adherent at baseline still need interventions and/or reminders to help them sustain their adherence level.
Post hoc test showed there was a difference in medication adherence between the PLUS and control group at 2 months and 9 months, but not PLUS and LITE groups. We also did not find a difference between PLUS group and LITE group in cardiac event-free survival. In previous studies MEMS report as feedback for medication-taking behavior was effective in improving medication adherence of HIV positive,30
smoking (adherence to bupropion),50
individuals and people with diabetes.36
It is unclear why we could not find a difference between PLUS and LITE groups. There are a few possibilities. First, feedback from the MEMS is to help patients with HF to understand their actual medication-taking behavior and track back on those days they missed doses. Then, it will be easier to help patients recognize their barriers of missing doses and find ways to target on those barriers. However, patients may have established and known their patterns of taking their medication and their reasons of missed doses without the help from a MEMS report.
Second is dose response. In the most effective studies, patients in the intervention group received more sessions of feedback intervention (3 to 7 sessions) than our study. It might take more than two sessions of feedback intervention to see their medication-taking patterns, identify the reasons of missed doses, and gain skills to adhere to their medications. Third, in two30, 36
of the effective feedback studies, patients in the intervention group were offered another type of MEMS caps during the intervention: the so-called SmartCap that displays how often it has been opened during that day and helps patients to increase their adherence. No matter which possibility is correct, the findings need to be verified in a larger sample size and recruiting more non-adherent patients in the future study.
Our findings should be interpreted with the following limitations in mind. First, it is assumed that patients take one dose of their prescribed medication after each MEMS bottle opening although this assumption could be questioned. The MEMS device is a valid, objective, and considered a “gold standard” measure to assess medication adherence in the current adherence literature.42
Prior researchers have demonstrated that opening of the bottle does, indeed, reflect actual medication taking,31, 34
and that use of the MEMS does not increase adherence artificially.35
However, we did not measure serum drug levels and cannot say with absolute certainty that when patients opened the MEMS cap, that they really took out the medication and consumed it. Our finding, however, of an association between increased medication adherence and improved outcomes make this likelihood quite small.
Another potential limitation has to do with the applicability of the MEMS to clinical practice. The use of the MEMS to measure medication adherence is likely too expensive and not practical in the clinical settings. Therefore, even though self-report measures are subject to recall bias and social desirability, it is important to develop a reliable and valid self-report instrument to measure medication adherence for researchers and clinicians in order to translate the results of this study to clinical settings.
Although we demonstrated significant differences (better medication adherence and less cardiac event) between intervention and control groups, a larger sample size of non-adherent HF patients is needed to generalize these results. This study had a total sample of 82 participants who were recruited from one Southern tertiary hospital. Our sample only included 36% non-adherent patients. Therefore, findings from this study warrant further study in a larger non-adherent sample. Finally, there were more married patients randomized to the intervention group than to the control group, and for this reason we adjusted for marital status in the multiple Cox regression.