Self-report instruments for assessing adherence to warfarin therapy: a systematic review

Abstract

Background

The assessment of adherence to warfarin therapy is useful in clinical practice due to its wide variability in dose–response and risks of complications. The aim of this study was to investigate validated instruments used to assess adherence to warfarin therapy.

Methods

Information was collected from the MEDLINE (PubMed), LILACS, EMBASE, and Cochrane Library databases. Search strategies were applied for each database, with no time limit or language restriction. Inclusion criteria consisted of study participants of ≥ 18 years of age, from both sexes, on chronic anticoagulation with warfarin for any indication and the use of validated instruments to assess adherence to warfarin therapy. Exclusion criteria consisted of duplicate articles, narrative or systematic reviews, and meta-analyses, as well as case reports/series and experimental studies involving animals. Two independent reviewers performed the following steps: evaluation of titles/abstracts, selection of studies after full reading, data extraction, and evaluation of potential bias. Discrepancies were resolved by a third reviewer.

Results

Overall, 19 articles were selected for this systematic review, including 17 cross-sectional studies, one cohort study, and one quasi-experimental study, published from 2009 to 2019. The validated instruments identified in this review were Morisky Medication Adherence Scale (MMAS), the eight-item Morisky Medication Adherence Scale (MMAS-8), Measurement of Treatment Adherence (MTA), and Brief Medication Questionnaire (BMQ). Only MMAS-8 was tested for reliability, using the internal consistency assessment, with Cronbach’s α range 0.56–0.71.

Conclusions

This review highlighted a gap in knowledge regarding the scarcity of validated instruments to assess adherence to warfarin therapy. Limitations were found in instruments that comprised the assessment of the isolated use of medication and the lack of analysis of other relevant therapeutic aspects. Future studies are needed to develop and validate more comprehensive instruments in an attempt to assess adherence to warfarin therapy.

PROSPERO

Registration number CRD42019128324

Appendices

Appendix 1 - Quality assessment of the included study, according to the Newcastle-Ottawa Scale

Study	Selection				Comparability	Outcome
	Representativeness of the exposed cohort	Selection of the non-exposed cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at the start of the study	Comparability of cohorts on the basis of the design or analysis	Assessment of outcome	Was followed up long enough for outcomes to occur	Adequacy of follow-up of cohorts	Total
Tang et al., 2017 [26]	1	1	1	1	1	2	1	1	9

Appendix 2 - Quality assessment of the included study, according to the ROBINS‐I tool of the Cochrane Library

Study	Lee et all., 2016 [20]
Bias due to confounding factors	Moderate
Bias in selection of participants into the study	Serious
Bias in classification of interventions	Moderate
Bias due to deviations from intended interventions	Moderate
Bias due to missing data	Moderate
Bias in measurement of outcomes	Serious
Bias in selection of reported results; Overall Bias	Low
	Risk of severe bias

Appendix 3 - Quality assessment of the included study, according to the Agency for Research and Health Quality (ARHQ) Methodology Checklist for Cross Sectional/Prevalence Studies

Ababneh et al, 2016 [13]

Balkhi et al., 2018 [14]

Bennaghmouch et al., 2019 [15]

Castelluci et al., 2015 [16]

Fernandes et al., 2019 [17]

Jorgensen et al., 2013 [18]

Kitahara et al., 2014 [19]

Obamiro et al., 2018 [21]

Oliveira Kamakura et al., 2019 [22]

Rolls et al., 2017 [23]

Shilbayeh et al., 2018 [24]

Souza, Colet and Heineck, 2018 [25]

Tulek et al., 2019 [27]

Volterrani et al., 2018 [28]

Wang, Kong and Ko, 2012 [29]

Yahaya et al., 2009 [30]

Zhao et al., 2017 [31]

1) Define the source of information (survey, record review)

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

Yes

Yes

yes

yes

2) List inclusion and exclusion criteria for exposed and unexposed subjects (cases and controls) or refer to previous publications

yes

yes

yes

yes

yes

no

no

yes

yes

yes

yes

yes

yes

Yes

Yes

yes

yes

3) Indicate time period used for identifying patients

yes

yes

yes

yes

yes

yes

yes

no

yes

no

yes

yes

yes

Yes

Yes

yes

yes

4) Indicate whether or not subjects were consecutive if not population-based

yes

yes

yes

yes

yes

unclear

yes

yes

yes

yes

yes

yes

yes

Yes

Yes

yes

yes

5) Indicate if evaluators of subjective components of study were masked to other aspects of the status of the participants

yes

no

no

yes

no

no

no

no

no

no

no

no

no

no

no

unclear

yes

6) Describe any assessments undertaken for quality assurance purposed (e.g., test/retest of primary outcome measurements)

no

yes

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

7) Explain any patient exclusions from analysis

no

no

yes

no

yes

no

no

yes

no

yes

yes

yes

no

no

yes

yes

yes

8) Describe how confounding were assessed and/or controlled

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

9) If applicable, explain how missing data were handled in the analysis

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

10) Summarize patient response rates and completeness of data collection

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

11) Clarify what follow-up, if any, was expected and the percentage of patients for which incomplete data or follow-up was obtained

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

no

Total

6

6

6

6

6

3

4

5

5

5

6

6

5

5

6

6

7