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Journals of Gerontology: Medical Sciences
cite as: J Gerontol A Biol Sci Med Sci, 2017, Vol. 00, No. 00, 1–7
Advance Access publication September 2, 2017
Research Article
Adherence and Persistence Among Statin Users Aged 65
Years and Over: A Systematic Review and Meta-analysis
Richard Ofori-Asenso, BPharm, MSc,1,2 Avtar Jakhu, BSc,1 Ella Zomer, BBiomedSci(Hons),
PhD,1 Andrea J. Curtis, BSc(Hons), PhD,3 Maarit Jaana Korhonen, LicSc (Pharm), PhD,4
Mark Nelson, MBBS (Hons), MFM, FRACGP, FAFPHM, PhD,5 Manoj Gambhir, BSc, PhD,2
Andrew Tonkin, MBBS, MD, FRACP, FCSANZ,6 Danny Liew, MBBS (Hons), BMedSc,
FRACP, PhD, CertHealthEcon,1 and Sophia Zoungas, MBBS, FRACP, PhD3,7,8
Centre of Cardiovascular Research and Education in Therapeutics (CCRET), Department of Epidemiology and Preventive Medicine,
Epidemiological Modelling Unit, Department of Epidemiology and Preventive Medicine, 3STAREE, Department of Epidemiology and
Preventive Medicine, and 4Centre for Medicine Use and Safety (CMUS), Faculty of Pharmacy and Pharmaceutical Science, Monash
University, Melbourne, Australia. 5Menzies Institute for Medical Research, University of Tasmania, Australia. 6Cardiovascular Research
Unit, Department of Epidemiology and Preventive Medicine, Monash University and 7Monash Centre for Health Research and
Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 8Diabetes and
Vascular Medicine Unit, Monash Health, Melbourne, Australia.
Address correspondence to: Sophia Zoungas, MBBS, FRACP, PhD, Department of Epidemiology and Preventive Medicine, Monash University,
5-6th Floor, Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia. E-mail:
Received: June 6, 2017; Editorial Decision Date: August 23, 2017
Decision Editor: Anne Newman, MD, MPH
Background: Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence
patterns among older statin users have not been comprehensively reviewed.
Methods: As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects,
CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/
or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling.
Results: Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up,
59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion
of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged
more than 75 years than those aged 65–75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion
of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users
were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year.
The proportion of statin users who were adherent based on self-report was 85.5%.
Conclusions: There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and
reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.
Keywords: HMG-CoA reductase inhibitors, Discontinuation, Cardiovascular disease prevention
The efficacy of statins in the prevention of cardiovascular diseases
(CVDs) has been well documented (1). Statins are used by over a
billion people globally (2) and are largely considered to be standardof-care such that new lipid lowering agents are investigated as addons to statins rather than as stand-alone treatments (3).
© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
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Journals of Gerontology: MEDICAL SCIENCES, 2017, Vol. 00, No. 00
However, despite the evidence supporting their clinical benefits,
as well being well tolerated by most patients and having a low cost
(for generic substitutes), many statin users fail to follow the prescribed dosing regimens (4,5). Studies have linked poor statin adherence and discontinuation to worse clinical outcomes, with significant
economic implications (5,6).
Statin use is widespread among older populations, being taken
by half of American men aged 65–74 years (7), as well as by 40%
of Australians aged 65 years and over (8). Further increases in statin
utilization are expected due to population ageing, and also as a result
of recent changes in cholesterol treatment guidelines recommending
the adoption of risk-based management approach (9). To achieve
the desired statin effect, optimal adherence is necessary. However, in
older patients, adherence to medication is particularly challenging
due to factors such as polypharmacy and increased susceptibility to
adverse events (10). The evidence supporting the use of statins in
the elderly, particularly for primary prevention, is also less clear, and
a matter of controversy (11). This is likely to further impact older
patients’ willingness to continue and adhere with treatment.
Despite the above, synthesized data on adherence and persistence
patterns among older statin users are limited; we have not identified any published systematic reviews that specifically address this
topic. While previous general reviews provided important information on statin adherence (4,5), they often focused on 12 months of
patient follow-up. It is unclear what the patterns of adherence and
persistence beyond this period are. In some instances, the distinction
between adherence and persistence has not been clearly made (12).
In the present study, we sought to (i) characterize the patterns of
adherence and persistence among older statin users and (ii) compare
adherence and persistence among primary and secondary prevention
users. This study was part of a larger review on the patterns and barriers to statin use among older people (13).
Search Strategy
The detailed protocol for our review on adherence/persistence and
their predictors among older statin users has been published (13).
We searched Medline, Embase, CINAHL, PsycINFO, Cochrane
CENTRAL, Database of Abstracts of Reviews of Effects (DARE),
and the National Health Service Economic and Evaluation Database
(NHSEED) through December 2016 to identify English articles
reporting adherence and/or persistence among older statin users.
The search terms adopted involved a combination of those related
to the intervention (ie, statins or HMG-CoA reductase inhibitors)
and outcomes (ie, adherence, persistence or discontinuation, etc.)
(Supplementary Table S1).
Study Selection and Evaluation
Articles reporting on adherence and/or discontinuation among older
statin users (aged ≥65 years) were eligible for inclusion. Studies utilizing any of a variety of methods including pill count, prescription
refill records or patient’s self-reports/recalls assessed via validated
scales were considered. For studies that measured adherence via
the medication possession ratio (MPR), proportion of days covered
(PDC) and proportion of doses taken (PDT), we included only those
in which adherence was dichotomized with an 80% cutoff. While
the 80% threshold is arbitrary, it is often cited to correspond to the
minimum adherence level required to achieve a satisfactory clinical
effect of statin treatment (12).
Persistence data were collected from studies that reported statin discontinuation. Studies on medication discontinuation usually
adopt the “permissible-gap” method whereby patients are considered to have discontinued treatment after exceeding the maximum
allowable period of no refill (12). The methodological quality of
the studies included in this report were assessed via a set of questions formulated with reference to the National Institute of Health
Quality Assessment Tool for Observational Cohort and CrossSectional Studies (14). This tool was selected based on its robustness
yet easy adaptability.
Data Extraction and Analysis
Two reviewers (R.O. and A.J.) extracted study data and authors
were contacted for unpublished data if necessary. When appropriate, meta-analysis using random-effect modeling techniques was
performed. Heterogeneity across studies was quantified via the I2
statistic (15). Assessment of publication bias was by direct observation of funnel plots and Egger’s regression test was used to assess
for statistical significance (16). The robustness of pooled estimates
was tested through leave-one-out sensitivity analyses (15). Subgroup
analyses based on anticipated sources of heterogeneity (eg, measurement technique, region of study, etc.) were performed. Statistical
significance was set at p less than .05. Analyses were undertaken
using StatsDirect Statistical Software (version 3.0, StatsDirect Ltd,
Cheshire, UK) and MetaXL.
Study Characteristics
A total of 93 articles were included in the current report (Figure 1).
We successfully linked 20 articles (as 9 studies) resulting in 82 unique
studies that reported data among 3,048,563 older statin users sampled from over 40 countries (Supplementary Table S2). The included
articles were published in the years 2002–2016, with the majority
(72.0%) published within the last 5 years (2012–2016). Among 45
studies involving 1,470,650 subjects for which gender breakdown
was available, 58.6% of the subjects were females. Per regional
distribution of studies, 45% were from North America, 40% from
Europe, 14% from the rest of the world, and 1% were cross-regional.
The studies included in the review were of reasonable quality, and
the majority (72%) were graded as good (Supplementary Figure S1),
and the remaining studies were graded as medium.
Patterns of Statin Adherence
Fifty-eight studies involving 2,274,890 subjects reported adherence
via assessment of database records (prescription, refill, or pharmacy
claims data) with duration of follow-up ranging from 6 months to
≥12.6 years. Of the 58 studies, 76% used the PDC method and 24%
used the MPR approach.
The most frequent follow-up period was 12 months; 39 studies
(60 datasets) reported 1-year adherence among 1,194,395 subjects.
The pooled proportion (Figure 2) of subjects adherent at 1-year was
59.7% (95% confidence interval [CI] 55.6–64.1). The proportion of
primary prevention subjects who were adherent at 1-year was 47.9%
(95% CI, 39.8–56.1), compared to 62.3% (95% C1 58.2–66.4) of
secondary prevention subjects (p value for difference <.0001). The
1-year adherence was higher among subjects aged 65–75 years than
those aged >75 years irrespective of statins being taken for primary (65–75 years = 49.6%, >75 years = 37.3%: p value for difference <.0001) or secondary prevention (65–75 years = 62.6%,
Journals of Gerontology: MEDICAL SCIENCES, 2017, Vol. 00, No. 00
Figure 1. Flow chart of systematic review process.
>75 years = 58.3%: p value for difference <.0001). Among studies
that used the MPR method, 58.5% (95% CI 48.9–67.7) of subjects
were adherent at 1 year, whereas 60.4% (95% CI 56.7–64.1) of
subjects in studies that utilized the PDC approach were adherent (p
value for difference <.0001). For new statin users, 51.8% (95% CI
42.6–61.0) were adherent within the first treatment year.
From the pooled data (Table 1), 59.9%, 59.6%, 55.3%, 35.9%,
35.7%, and 28.4% of older statin users were adherent at 6 months,
2, 3, 4, 5, and ≥10 years, respectively. The 6-month, 1, 2, and 3-year
pooled adherence were unchanged by a leave-one-out sensitivity
analyses (plots not shown). Funnel plot assessments showed no
obvious evidence of publication bias (Supplementary Figure S2) and
this was confirmed via Egger’s regression results for 6 months (p
value = .661), 1 year (p value = .6263), 2 years (p value = .5061),
3 years (p value = .4933), 4 years (p value = .4493), 5 years (p
value = .4987), and ≥10 years (p value = .2442).
Three other observational studies involving 190 subjects measured adherence using validated self-reporting scales; 85.5% (95%
CI 77.6–92.1, I2 = 0.99) of the subjects were adherent based on
Patterns of Statin Persistence
Thirty-three studies involving 872,098 subjects reported proportion of patients persisting with treatment. The majority (67%) of
studies adopted the permissible gap method, that is, they defined
a maximum break in refill beyond which patients were deemed to
have discontinued treatment (12). However, significant disparities in
the criteria applied were evident (eg, the permissible gap varied from
30 days to 365 days). The inconsistencies precluded the conduct
of a meta-analysis. Instead, we summarized the data descriptively
using median and interquartile range (IQR) as adopted in other
medication utilization reviews (17). We did not report the summary data in the form of range because the intervals were extremely
wide (Supplementary Figure S3). Statistical estimates of differences
between groups were not assessed as variance would have been
underestimated (18). Median was not computed when data were
available from less than four studies.
Figue 2. Proportion of subjects adherent at 1-year follow-up.
Twenty-six studies (49 datasets) involving 742,691 subjects
reported persistence for 1 year. The overall proportion of older statin
users persistent at 1 year was 76.7% (IQR 71.4–87.4). Among primary prevention subjects, 76.0% (IQR 39.5–85.0) were persistent
at 1 year compared with 82.6% (65.0–88.8) of secondary prevention subjects. For new statin users, 76.1% (IQR 71.1–82.8) persisted
with treatment at the first anniversary.
The median proportion of users persistent at 6 months, 2, 3,
and 4 years was 82.6%, 68.1%, 63.3%, and 61.2%, respectively
(Table 2). Few studies reported persistence at 5 and ≥10 years follow-up, 2 and 1, respectively. In all of these studies, the proportion of
patients persistent was less than 60%. Three studies did not involve
a specific year of follow-up and median was not computed.
We report suboptimal statin use among older patients, with 40%
nonadherence at 1 year and more than one-third discontinuing
treatment by 3 years. Although recent (2012–2016) publications
Journals of Gerontology: MEDICAL SCIENCES, 2017, Vol. 00, No. 00
Table 1. Proportion of Older Statin Users Adherent at Various Follow-up Periods‡
Follow-up Period
6 mo
Assessment method
Statin indication*
Primary prevention
65–75 y
>75 y
Secondary prevention
65–75 y
>75 y
Participant Type
New Users
Mixed patients
Region of Study
North America
Rest of the world
Publication period
≥10 y
Number of Studies
Sample Size
% Adherent (95% CI)
I2 Statistic
59.9 (57.3–66.0)
59.7 (55.6–64.1)
58.5 (48.9–67.7)
60.4 (56.7–64.1)
47.9 (39.7–56.1)
49.6 (43.5–55.7)
37.3 (20.0–56.5)
62.3 (58.2–66.4)
62.6 (52.6–71.9)
58.3 (44.4–71.5)
51.8 (42.6–61.0)
63.5 (59.5–63.7)
61.5 (57.1–65.8)
57.9 (50.7–64.9)
54.1 (41.9–66.0)
61.9 (58.3–65.3)
59.6 (49.6–61.9)
55.3 (46.6–63.9)
35.9 (14.3–61.0)
35.7 (19.2–54.0)
28.4 (13.3–46.3)
57.5 (50.3–64.5)
Note: CI = Confidence interval; MPR = Medication possession ratio; PDC = Proportion of days covered.
Only studies that reported adherence via assessment of database records (MPR or PDC) are included in this table. *The majority of studies involved mix of
patients but did not stratify results according to indication nor by age group (65–75 vs >75); †no specific defined year (eg, 18 mo, 4.3 y, etc.).
reported slightly higher adherence and persistence than earlier ones,
the trend is notable for a population at increased risk of cardiovascular events in whom more than 80% of CVD-related deaths occur
(19). It appears that the first 180 days of follow-up is the most critical period when many patients become nonadherent or discontinue
treatment. Nonetheless, we observed no clear evidence of plateau in
the adherence or persistence rates during follow-up, suggesting the
need to provide long-term treatment support.
The high self-reported adherence observed in our study is consistent with previous research, that suggest that adherence measured
via self-reporting scales or patient interviews tend to overestimate
levels of medication use for multiple reasons that include recall
and social desirability bias (20). Thus, while assessment of adherence via self-reports may be time saving, inexpensive and easy to
apply in routine clinical practice (20), the value of using them to
understand how well patients are following the statin dosing regimen is low.
There is strong evidence supporting the long-term use of statins
to achieve the desired effects both on cardiovascular morbidity and
mortality. In the Scandinavian Simvastatin Survival Study (4S) trial,
the biochemical effect of simvastatin was observed after a few weeks
of treatment but the effects on coronary artery disease morbidity and
mortality were only observed after approximately 24 months (21).
However, as per our analysis, nearly one in four patients newly initiated on statin discontinued within the first 12 months of treatment.
It is possible that patients stopped treatment as a result of poor drug
effectiveness or due to adverse effects especially as ageing may result
in altered pharmacokinetics and pharmacodynamics. Nonetheless,
an analysis of the tolerability of 4,924 older people in 50 statin trials showed that only 2.1% of treatment discontinuation was due to
adverse events (22). Similarly, in a retrospective cohort study with
over 100,000 patients, more than half discontinued statin treatment
but less than 4% of discontinuers cited adverse effects as the reason
for discontinuation (23).
The perceived benefits or susceptibility to disease as explained by
the Health Belief Model has been shown to positively correlate with
patients’ behavior (24). Since dyslipidaemia is an asymptomatic condition, patients may be unaware of their risk of adverse health outcomes. Statin users who have experienced an event (eg, myocardial
infarction [MI], ie, secondary prevention) may consider themselves
to be at higher risk, as well as exhibit greater belief in the severity
of the diseases being prevented and may therefore be more committed to treatment (24). Kronish and colleagues (25) reported that
among older patients who were nonadherent to statins, 38% became
adherent following hospitalization for acute MI. Thus, perception of
low risk may partly explain the poorer adherence and persistence
observed among the primary prevention subjects. Nonetheless, considering that only 62% of the secondary prevention subjects in our
study were adherent at 1 year, other factors beyond probabilistic
information (ie, benefit or risk) may additionally contribute to determining patients’ behavior.
Polypharmacy is prevalent among older populations and the
risk of drug–drug interactions (DDIs) increases with the number of
medications. For example, a patient on five to nine medications has
Journals of Gerontology: MEDICAL SCIENCES, 2017, Vol. 00, No. 00
Table 2. Proportion of Older Statin Users Persistent at Various Follow-up Periods
Follow-up Period
Number of Studies
Sample Size
% Persistent (IQR)
6 mo
Assessment method
Statin indication‡
Primary prevention
Secondary prevention
Participant Type
New Users
Mixed patients
Region of Study
North America
Rest of the world
Publication period
82.6 (71.1–89.0)
76.7 (71.4–87.4)
76.0 (71.0–82.4)
87.7 (80.2–88.8)
76.0 (39.5–85.0)
82.6 (65.0–88.8)
76.1 (71.1–82.8)
83.0 (73.5–88.6)
65.0 (57.7–88.0)
76.8 (74.1–85.6)
61.0 (41.3–73.9)
80.2 (76.3–88.3)
68.1 (46.7–76.3)
63.3 (60.3–68.7)
61.2 (58.4–70.6)
Note: IQR = Interquartile range.
*The permissible gap varied from 30 days to 365 days across studies; †Other includes for instance reliance on patient reports; ‡The majority of studies did not
stratify results according to statin indication and were excluded from this analysis.
about 50% probability of experiencing a DDI and this increases to
100% when the number of medications exceeds 20 (26). In addition,
metabolism enzymes become less functional at advanced ages resulting in increased statin area under the curve (AUC) and higher likelihood of DDIs. Side effects are also common when more medications
are used, with as much as 40% of hospitalizations in older patients
attributed to adverse drug events (26). As a result, increasing polypharmacy has frequently been correlated with poor statin adherence
(6). Older patients may also experience significant cognitive decline
as well as face other barriers (eg, difficulty in swallowing) which may
all affect adherence (10).
In recent years also, there has been intensified debate around the
use of statins in older adults (11). Analyses from several countries
including the United Kingdom (27) and Denmark (28) indicate that
the polarized views on the interpretation of the effects of statin treatment have had adverse impacts on patients’ adherence and continuation rates. In the very old (>75 years) particularly, guidelines suggest
a lack of evidence to support the use of statins for primary prevention (29). This may partly explain the worst adherence observed
among subjects aged more than 75 years who were taking statins for
primary prevention.
Ongoing trials such as STAREE (NCT02099123) and SITE
(NCT02547883) will provide important evidence about the use of
statin for primary prevention in the elderly. STAREE will examine
whether treatment with atorvastatin 40mg/day versus placebo in
healthy elderly individuals (≥70 years) will prolong overall survival
or disability-free survival. SITE will evaluate the cost-effectiveness
of stopping statins in people aged ≥75 years—the primary endpoints
being overall mortality and incremental cost per quality-adjusted
life-year (QALY) gained. The results of both STAREE and SITE are
expected after 2020.
The clinical implications of our findings are important. There is
increasing evidence linking poor statin adherence and discontinuation
to worse clinical outcomes (5). For example, patients who discontinue statin treatment following MI are about 3 times more likely to
die than those continuing treatment (30). Compared with adherent
patients, those nonadherent to statins and antihypertensive medications also have more than sevenfold increased risk of fatal stroke
(31). Unsurprisingly, a meta-analysis attributed nine excess CVD
deaths per 100,000 to nonadherence to cardiovascular medications
including statins (5). The observed poor statin adherence and persistence may also be indicative of widespread suboptimal preventive
medication use among the older population. Indeed, some studies
suggest that nonadherence to one medication class may predict suboptimal use of another. Among 2,695 older Americans who initiated statin treatment following hospitalization for acute MI, low
adherence to antihypertensive medications was associated with 62%
increased risk of statin nonadherence (32).
The economic impact of not using prescribed medications is significant, with studies frequently associating poor statin adherence and
discontinuation with lower cost-effectiveness (33). In most developed
countries, CVDs attract higher costs than any other disease class. In
six European countries (France, Germany, Spain, Italy, Sweden, and
the United Kingdom), the total financial impact of CVDs exceeded
€102 billion in 2014 (34). The use of evidence-based pharmacological therapies such as statins remains the cornerstone of CVD prevention and treatment. Thus, poor adherence/persistence represents a
missed opportunity to realize the full clinical potential of preventive
therapies that are intended to reduce CVD burden. Consequently, in
the United States alone, the yearly economic loss due to medication
nonadherence has been estimated as $290 billion (35).
It has been noted that if adherence to prescribed medications
were to improve, it would have far greater impact on population health than improvement in specific medical treatments (36).
Interventions targeted at patients and health professionals are
necessary to address the poor statin adherence and persistence.
Journals of Gerontology: MEDICAL SCIENCES, 2017, Vol. 00, No. 00
Patient counseling/education, reinforcement and reminders have
been observed to improve adherence (37). A Cochrane review
found reinforcement and reminders increased adherence by about
24% (38). Strategies that seek to enhance patient–physician communication or those aimed at minimizing regimen complexity
have also shown some degree of success (37). Other interventions
that target the health delivery system such as through provision
of extended care via ancillary health staff or those meant to eliminate health system cost-containment measures such as copayments
have been considered necessary (6). Ito and colleagues for instance
demonstrated that providing full medication reimbursement (for
cardiovascular drugs including statins) to post-MI patients is costeffective (39). However, in view of the complexity of the drivers of
suboptimal adherence/persistence, the greatest improvements are
likely to be achieved via the adoption of a mix of patient-tailored
long-term interventions (6,36–38).
This review has some limitations. First, studies do not report
in detail actual reasons for nonadherence or discontinuation. It is
possible that some discontinuation was due to adverse effects or
initiated by clinicians. Second, adherence/persistence was based on
indirect measurements and we cannot ascertain whether patients
actually took the medication (12). Third, we restricted our study
to English articles, and this is likely to limit the generalizability.
Fourth, patients who discontinue statins may reinitiate treatment
and this has not been incorporated in our analysis. Fifth, although
some publications have offered guidance regarding the definitions and measurement of medication adherence and persistence
(12), we noticed significant inconsistencies in the literature particularly with regards to the assessment of statin discontinuation.
Persistence was therefore analyzed descriptively, although, metaanalysis would have provided a more robust outcome. Finally,
we observed heterogeneity (I2 > 90 in many cases) which may be
attributed to multiple factors including patient characteristics and
data sources.
Our study has important strengths worth mentioning. We
applied a specific adherence cutoff ensuring consistency across
studies. No geographic or time restrictions were imposed allowing
the inclusion of a large body of evidence. Contact made with study
authors ensured the inclusion of a large amount of unpublished
data allowing us to provide for the first time a pooled estimate
of self-reported statin adherence. To our knowledge, ours is the
first systematic review to offer some understanding of the patterns
of long-term (>1 year) adherence and persistence among statin
users. Our pooled adherence estimates are robust and the absence
of publication bias supports the reliability of our findings. Lastly,
considering that >70% of the included studies were recently published, our reported adherence and persistence estimates may speak
to current trends.
There is poor short and long-term adherence and persistence among
older statin users. Strategies to improve adherence and reduce discontinuation are needed to close the gap if the intended cardiovascular benefits of statin treatment are to be realized.
Supplementary Material
Supplementary data is available at The Journals of Gerontology,
Series A: Biological Sciences and Medical Sciences online.
R.O. is sponsored by a Monash Graduate Scholarship and Monash International
Postgraduate Research Scholarship for his doctoral studies. S.Z. is funded by
a National Health and Medical Research Council Senior Research Fellowship.
No other funding has been required to undertake this work.
We are grateful to authors who generously provided us with unpublished data.
We also thank Lorena Romero, a Senior Medical Librarian (Ian Potter Library,
Alfred Hospital, Melbourne, Australia) who reviewed our initial search strategy and provided useful feedback.
Conflict of Interest
S.Z. reports past participation in advisory boards and/or receiving honoraria from: Amgen Australia; AstraZeneca/Bristol-Myers Squibb Australia;
Janssen-Cilag; Merck, Sharp, and Dohme (Australia); Novartis Australia;
Novo Nordisk; Sanofi; Servier Laboratories; Takeda Australia; and Monash
University (undertaking contract work for AstraZeneca Pty Limited/BristolMyers Squibb Australia Pty Limited) for work unrelated to this study.
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