In our prospective cohort of patients undergoing warfarin therapy, higher education level, current employment, and lower scores on mental health and cognitive functioning were associated with poor adherence to warfarin therapy.
The association between active employment and poor adherence to warfarin is consistent with the finding of Palareti et al
. who reported active employment as risk factors for INR instability.8
Moreover, a link between poor adherence and active employment has also been noted in other disease settings.23
Although the underlying relationship is not certain, active employment might reflect numerous competing interests which take precedence over consistent pill-taking. The finding of decreased adherence among those with higher educational attainment is consistent with a previous case–control study of dropouts from warfarin clinic.24
Poor adherence by more educated subjects might relate to more independent decision making or, as has been suggested in other settings, to decreased trust in physicians relative to less educated subjects.25
Among the psychosocial variables studied, low cognitive functioning and lower mental health functioning stood out as risk factors for poor adherence to warfarin. Cognitive scores were not associated with warfarin adherence in a prior study that used patient self-report as a means to measure adherence,26
but poor cognition has been related to nonadherence to other medications in elderly patient populations.27
Lower self-assessed mental health status (as scored on the SF-36) has also been associated with worse self-reported adherence in other areas:28
We found no association between adherence to warfarin and depressive symptom scores, in contrast to selected reports in settings such as anti-hypertensive medication use.12
Nearly all of the health care access, utilization, and pill-taking practice variables in our study failed to demonstrate close associations with warfarin adherence. However, these factors varied little among our patients, in part because specialized anticoagulation clinics limit this variability in practice. Thus, we cannot exclude these as important factors outside of specialized clinics or in other settings.
The strengths of our investigation are the prospective design; comprehensive examination of demographic, clinical, psychosocial, health utilization, and pill-taking practice variables; and precision of assessment of the outcome of adherence by use of MEMS cap data. Limitations include, first, the large number of variables analyzed, which could have led to false positive findings. However, all variables included were hypothesized a priori to be associated with adherence. Second, we may not have detected factors with relatively small effects on adherence. Third, there may be selection bias in terms of the subjects willing to agree to psychosocial evaluation and MEMS cap monitoring, although there were no significant differences in baseline demographic factors compared to those who declined MEMS cap monitoring.
A fourth limitation involved use of MEMS caps to measure adherence. This method raised design challenges as many patients used MEMS caps as a diary while they employed a pillbox reminder system to organize all of their medications. The higher odds of nonadherence associated with this practice may be explained by study subjects’ forgetting to activate the MEMS cap after taking their medications directly from their pillbox. Another possibility is that patients who need pillbox reminders have worse overall adherence. Regardless, we accounted for this practice by adjusting for use of MEMS cap as a diary in our multivariable model. We had insufficient sample size to limit the analysis to only visits where MEMS caps were used directly on pill bottles. However, our prior study demonstrated that nonadherence to warfarin was closely linked to out of range INR values both in those who used the MEMS cap as a diary and those who accessed their warfarin directly from the MEMS cap container.4
Lastly, although derived from subjects recruited from two different centers, our study findings may not generalize to warfarin management outside of specialized anticoagulation clinics.
In summary, poor adherence to warfarin appears most strongly associated with patient-level factors related to time, memory, and mental health functioning. Within the carefully controlled anticoagulation clinic setting, health utilization variables, and pill-taking practices were not associated with adherence but there was limited variability of these factors in our cohort. These results suggest that in the anticoagulation clinic setting, interventions to improve adherence should focus on memory prompts and evaluation of patient priorities rather than system-level variables.
- Warfarin is one of the most prescribed medications in the United States and serves as the gold standard therapy to prevent both stroke and venous thromboembolism
- Poor adherence is a major contributor to poor anticoagulation control. However, relatively little is known about risk factors for poor adherence with daily warfarin use
- In our prospective cohort study of 111 adults monitored via electronic MEMS caps, over 20% of doses were taken incorrectly
- Factors independently associated with nonadherence included education beyond high school, current employment, lower mental health functioning, and poor cognition. Other pill-taking practices and indices of health care access and utilization were not closely associated with poor adherence to warfarin
- Within the carefully controlled anticoagulation clinic setting, these patient-specific factors may be the basis of future interventions to improve nonadherence