Interventions to improve adherence to lipid-lowering drugs: a systematic review and meta-analysis

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The review was reported in adherence to PRISMA guidelines and followed a protocol available on Open Science Framework.

“This review was reported in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines,8 following a protocol available at Open Science Framework (https://osf.io/9gx5h).”

• cites [8] Moher, 2009, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, BMJ sourceSupported

Classified as probably not a substantial claim.

The search period began in 2016 to ensure continuity with and update the previous review by van Driel et al. (2016).

“The search period began in 2016 to ensure continuity with and update the previous review by van Driel et al. (2016).6”

• cites [6] van Driel, 2016, Interventions to improve adherence to lipid-lowering medication, Cochrane Database Syst Rev sourceSupported

Classified as probably not a substantial claim. May combine two claims.

van Driel et al., 2016 described 7 categories of interventions and demonstrated their potential to enhance adherence and improve clinical outcomes.

“van Driel et al., 2016 described 7 categories of interventions (simplifying drug regimen, patient education, intensified patient care, behavioural approaches, decision support systems, administrative process improvements, pharmacy-led interventions) and demonstrated their potential to enhance adherence and improve clinical outcomes.6”

• cites [6] van Driel, 2016, Interventions to improve adherence to lipid-lowering medication, Cochrane Database Syst Rev sourcePartly supported

  The Results matrix lists the seven intervention categories. The Discussion reports improved adherence and cholesterol levels for intensified patient care, but says several other categories did not consistently improve adherence or physiological outcomes. Thus the claim overstates the evidence if it attributes demonstrated benefits to all seven categories. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Cochrane Risk-of-Bias tool (ROB-2) was used to evaluate risk of bias, with two reviewers independently assessing each study.

“The Cochrane Risk-of-Bias tool (ROB-2) was used to evaluate the risk of bias within the included studies.19,20 2 reviewers independently assessed each study, resolving discrepancies through discussion or consultation with a third author.”

• cites [19] Higgins, 2002, Quantifying heterogeneity in a meta-analysis, Stat Med sourceNot checked — no full text of the source
• cites [20] Sterne, 2019, RoB 2: a revised tool for assessing risk of bias in randomised trials, BMJ sourceSupported

May combine two claims.

Reasons for poor adherence to lipid-lowering medications are multifactorial, including polypharmacy, lack of understanding of why LLMs are needed, fear of side effects, and misconceptions about hypercholesterolaemia as a condition requiring medication.

“Reasons for poor adherence to LLMs are multifactorial in nature. Polypharmacy, a lack of understanding of why LLMs are needed, fear of true or perceived side effects, misconceptions about hypercholesterolaemia as a condition requiring medication, are all factors which can compromise adherence.4”

• cites [4] Mehta, 2024, Non adherence to lipid-lowering therapy and strategies to improve adherence, Indian Heart J sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Health outcomes may also be influenced by comorbidities such as depression, which is prevalent among individuals with cardiovascular disease.

“Health outcomes may also be influenced by comorbidities such as depression, which is prevalent among individuals with cardiovascular disease.82”

• cites [82] Goldstein, 2017, Relationship between depression and medication adherence in cardiovascular disease: the perfect challenge for the integrated care team, Patient Prefer Adherence sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

We adopted van Driel et al.'s, 2016 intervention categorisation for ease of comparison, which may have introduced classification biases.

“Furthermore, we adopted van Driel et al.'s, 2016 intervention categorisation for an ease of comparison,6 which may have introduced classification biases.”

• cites [6] van Driel, 2016, Interventions to improve adherence to lipid-lowering medication, Cochrane Database Syst Rev sourceSupported

May combine two claims.

In the clinical setting, inadequate treatment to achieve LDL-C targets is a persistent issue, with physician inertia contributing to suboptimal dosing or utilisation of LLMs and their combinations.

“In the clinical setting, inadequate treatment to achieve LDL-C targets is a persistent issue, with physician inertia contributing to suboptimal dosing or utilisation of LLMs and their combinations.74, 75, 76, 77, 78, 79”

• cites [74] Cinza-Sanjurjo, 2024, Achievement of LDL-cholesterol goals in patients receiving LLT in primary care: TERESA-AP study: LDL-cholesterol goals in primary care, Cardiovasc Ther sourceSupported
• cites [75] Lee, 2021, Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia–Pacific region, Lipids Health Dis sourcePartly supported

  The Introduction sections on lipid-lowering treatments and barriers to goal attainment report that many patients miss LDL-C targets and that physicians in several Asia–Pacific countries are reluctant to prescribe high-dose statins. They support the point about suboptimal dosing, but do not establish that physician inertia causes underuse of combinations of lipid-lowering medicines; the paper discusses combinations as guideline recommendations. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [76] Marquina, 2022, Attainment of low-density lipoprotein cholesterol goals in patients treated with combination therapy: a retrospective cohort study in primary care, J Clin Lipidol sourceNot checked — no full text of the source

May combine two claims.

Single-component interventions (categorised as attitudinal, reward, educational, or technical) were most efficacious in the short term (<10 months), whereas multicomponent interventions (strategies consisting of more than 1 category) yielded better long-term medication adherence (≥10 months).

“This is in-line with Wiecek et al.'s (2019) findings, which showed that single-component interventions (categorised as “attitudinal”, “reward”, “educational”, or “technical”) were most efficacious in the short term (<10 months), whereas multicomponent interventions (strategies consisting of more than 1 category) yielded better long-term medication adherence (≥10 months).59”

• cites [59] Wiecek, 2019, Temporal effectiveness of interventions to improve medication adherence: a network meta-analysis, PLoS One sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The predominance of indirect measures could be due to the accessibility of pharmacy data and the objectivity of this metric, making indirect measures ideal for clinical research.

“This could be due to the accessibility of pharmacy data and the objectivity of this metric, making indirect measures ideal for clinical research.61”

• cites [61] Lam, 2015, Medication adherence measures: an overview, BioMed Res Int sourcePartly supported

  Section 4 (page unavailable) says prescription-refill records are popular in research because they permit analysis of large populations, but obtaining a complete dataset requires a centralized computerized system and consistent records. Section 8 (page unavailable) favors pharmacy-refill measures for large research populations when balancing accuracy and cost. The paper does not say pharmacy data are generally accessible or that all indirect measures are ideal for clinical research. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

We were not able to assess publication bias as none of the outcomes studied included more than 10 studies, which is a pre-requisite according to Cochrane's recommendations.

“We were not able to assess publication bias as none of the outcomes studied included more than 10 studies, which is a pre-requisite according to Cochrane's recommendations.83”

• cites [83] Page, 2024, Chapter 13: assessing risk of bias due to missing evidence in a meta-analysis sourceCould not verify

  The Abstract defines publication bias, and the discussion of ROB-ME mentions funnel plots and tests for asymmetry, but neither passage states a ten-study prerequisite. A search for that threshold and for Cochrane guidance found no supporting passage in our copy. The paper also cannot establish how many studies were included in the citing authors’ outcomes. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

While less reliable in the research setting, subjective measures can offer practical insights to barriers to adherence to facilitate tailoring interventions to a specific patient.

“While less reliable in the research setting, subjective measures can offer practical insights to barriers to adherence to facilitate tailoring interventions to a specific patient.61”

• cites [61] Lam, 2015, Medication adherence measures: an overview, BioMed Res Int sourceSupported

May combine two claims.

While 2 studies noted the presence of depression, neither explored impact on adherence outcomes or quality of life.

“While 2 studies noted the presence of depression, neither explored impact on adherence outcomes or quality of life.27,40”

• cites [27] Choudhry, 2018, Effect of a remotely delivered tailored multicomponent approach to enhance medication taking for patients with hyperlipidemia, hypertension, and diabetes: the STIC2IT cluster randomized clinical trial, JAMA Intern Med sourceSupported
• cites [40] Campbell, 2023, Self-management support using advertising principles for older adults with low income at high cardiovascular risk: a randomized controlled trial, Circulation sourceSupported

May combine two claims.

Six distinct interventions were employed; most were conducted in primary care settings and employed intensified patient care.

“6 distinct interventions were employed; most were conducted in primary care settings and employed intensified patient care.”

May combine two claims.

Short-term interventions (≤6 months) showed stronger effects than long-term follow-up (>6 months), which showed no significant benefit.

“short-term interventions (≤6 months) showed stronger effects compared to long-term follow-up (>6 months), which showed no significant benefit (SMD 0.35, 95% CI [0.15, 0.54]; OR 1.59, 95% CI [1.21, 2.08]).”

May combine two claims.

The systematic review included 35 studies and the meta-analysis included 15 studies.

“The systematic review and meta-analysis included 35 and 15 studies, respectively.”

• Also stated in: § Included studies · plain

  “Finally, 35 articles were included in the systematic review, with 15 used for meta-analysis.”

The quote only partly states this claim.

Pooled estimates showed no significant differences between intervention and control groups for physiological outcomes (HDL-C, LDL-C, TC, TG).

“Pooled estimates suggest no differences in physiological outcomes between the groups.”

May combine two claims.

Despite overall improvement in medication adherence observed in both continuous and dichotomous outcomes, we found no significant improvements in physiological outcomes like TC and LDL-C.

“Despite the overall improvement in medication adherence observed in both continuous and dichotomous outcomes, we found no significant improvements in physiological outcomes like TC and LDL-C.”

May combine two claims.

Overall, there was a significant improvement in medication adherence, as demonstrated by both continuous and dichotomous measures.

“Overall, there was a significant improvement in medication adherence, as demonstrated by both continuous and dichotomous measures.”

May combine two claims.

Indirect measures of medication adherence were the most common, with PDC being the metric of choice for most studies that utilised indirect measures of medication adherence.

“Indirect measures of medication adherence were the most common, with PDC being the metric of choice for most studies that utilised indirect measures of medication adherence.”

May combine two claims.

In our analysis, interventions that employed intensified patient care, complex behavioural intervention, and patient education and information were the most common.

“In our analysis, interventions that employed intensified patient care, complex behavioural intervention, and patient education and information were the most common.”

May combine two claims.

Most studies did not standardise dosing and titration of LLMs according to physiological targets, nor did they control diet or physical activity levels.

“Most studies did not standardise dosing and titration of LLMs according to the said physiological targets, nor did they control diet or physical activity levels, which likely explains the lack of differences in physiological outcomes between intervention and control groups.”

May combine two claims.

Interventions classified as complex behavioural interventions that target both patient-related factors and social and economic factors were more successful in improving adherence, with significant improvements across adherence outcomes, reported both as continuous and dichotomous outcomes.

“In contrast, interventions which we have classified as “complex behavioural interventions” that target both “patient-related factors” and “social and economic factors” were more successful in improving adherence, with significant improvements across adherence outcomes, reported both as continuous and dichotomous outcomes.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Language restrictions were not applied to broaden the search of relevant studies.

“Language restrictions were not applied to broaden the search of relevant studies.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data extraction for included studies was performed independently by two reviewers using an extraction form.

“Data extraction for included studies were performed independently by 2 reviewers using an extraction form documenting study, group, and outcome codes.”

Probably not a substantial claim: may not pass S3 (load-bearing).

19 studies reported blinding of personnel or outcome assessors.

“19 studies reported blinding of personnel or outcome assessors.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The GRADE tool was employed to assess the quality of evidence for outcomes in the meta-analysis.

“The international Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool (GRADEpro GDT) was employed to assess the quality of evidence for the outcomes explored in the meta-analysis.21”

• cites [21]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Almost half of the studies indicated clear randomisation processes to assign participants, 4 studies scored high risk in this domain, and others had uncertainty due to unclear or unreported allocation concealment.

“While almost half of the studies indicated clear randomisation processes to assign participants, 4 studies scored “high risk” in this domain, and others had uncertainty due to unclear or unreported allocation concealment.”

May combine two claims.

Risk of bias due to missing outcome data was low; only 2 studies had high risk.

“Risk of bias due to missing outcome data was low; only 2 studies had high risk.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Two reviewers independently examined each study, resolving discrepancies through discussion or consultation with a third reviewer.

“2 reviewers independently examined each study, resolving discrepancies through discussion or consultation with a third reviewer.”

May combine two claims.

Studies with high risk of bias were affected by the randomisation process, deviations from intended interventions, and selective reporting of outcome data.

“Studies with “high risk” were affected by the randomisation process, deviations from intended interventions, and selective reporting of outcome data.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Publication bias was not performed as none of the outcomes had more than 10 studies available.

“Nonetheless, publication bias was not performed as none of the outcomes had more than 10 studies available.”

May combine two claims.

Current interventions bring about improvements in medication adherence, but such improvements are not sustained over the long-term.

“Current interventions bring about improvements in medication adherence, but such improvements are not sustained over the long-term.”

May combine two claims.

Following worst-case scenario analysis, 3 studies were assessed as low risk, 11 as high risk, and 21 as unclear risk of bias.

“A risk-of-bias assessment following worst-case scenario analysis assessed 3 studies as “low risk”, 11 as “high risk”, and 21 as “unclear risk”.”

• Also stated in: § Risk-of-bias · plain

  “Following worst-case scenario analysis, studies were categorised as “low risk” (n = 3), “high risk” (n = 11), and “unclear risk” (n = 21).”

May combine two claims.

Oñatibia-Astibia et al., 2021 focused on the potential of community pharmacist interventions on improving adherence to LLMs and clinical outcomes, but their impact on clinically-relevant outcomes remains insufficiently explored.

“Oñatibia-Astibia et al., 2021 focused on the potential of community pharmacist interventions on improving adherence to LLMs and clinical outcomes.7 However, their impact on clinically-relevant outcomes remains insufficiently explored.”

• cites [7] Oñatibia-Astibia, 2021, Community pharmacist interventions to improve adherence to lipid lowering medication and their influence on clinical outcomes: a systematic review and meta-analysis, J Eval Clin Pract sourceNot checked — no full text of the source

May combine two claims.

GRADE quality of evidence was high for HDL-C, moderate for LDL-C, high for TC, and low for TG.

“medication adherence measured as a continuous variable: moderate; medication adherence measured as a dichotomous variable: high; HDL-C: high; LDL-C: moderate; TC: high; TG: low.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Study design, result inconsistency, indirectness of evidence, imprecision, and publication bias are factors which affect the quality of evidence.

“Study design, result inconsistency, indirectness of evidence, imprecision, and publication bias are factors which affect the quality of evidence.22”

• cites [22] Schünemann, 2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Reporting quality was inconsistent; some reported all outcomes, but others did not specify or register analysis plans in advance.

“Reporting quality was inconsistent; some reported all outcomes, but others did not specify or register analysis plans in advance.”

May combine two claims.

Prior systematic reviews did not provide sufficient information on how adherence was measured, nor assessment of physiological outcomes, and lacked information on evaluation of adverse events.

“However, these reviews did not provide sufficient information on how adherence was measured, nor assessment of physiological outcomes, and lacked information on evaluation of adverse events.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The analysis followed the intention-to-treat (ITT) principle.

“The analysis followed the intention-to-treat (ITT) principle, with a significant level of 0.05 set for two-sided tests.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The WHO framework emphasises the need to address healthcare team and system-related factors.

“This further cements the important applications of the WHO framework which emphasises the need to address healthcare team and system-related factors.60”

• cites [60] 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Medication adherence is influenced by numerous factors, including patient characteristics, medication-related issues, physician practices, and system-based factors.

“This highlights the complex nature of medication adherence, which is influenced by numerous factors, including patient characteristics, medication-related issues, physician practices, and system-based factors.58”

• cites [58] Yap, 2016, Systematic review of the barriers affecting medication adherence in older adults, Geriatr Gerontol Int sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The lack of significant differences in health outcomes in studies with comorbidities could be a result of under-powering of the studies.

“This could be a result of under-powering of the studies since the presence of comorbidities would necessitate for a larger sample size to show a difference.”

Classified as probably not a substantial claim.

The World Health Organisation (WHO) defines 5 dimensions of medication adherence: social and economic factors, healthcare team and system-related factors, condition related factors, therapy related factors, and patient-related factors.

“According to the World Health Organisation (WHO), there are 5 dimensions of medication adherence, each encompassing multiple factors—social and economic factors, healthcare team and system-related factors, condition related factors, therapy related factors, and patient-related factors.60”

• cites [60] 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Presence of concomitant medications, comorbidities, and duration of medication use can affect medication adherence, clinical outcomes, and health outcomes.

“As the presence of concomitant medications, comorbidities, and duration of medication use can affect medication adherence, clinical outcomes, and health outcomes (e.g., quality of life measures, biomarkers like LDL-C), future studies should take care to report such data and stratify results according to the presence of comorbidities and concomitant medications.84”

• cites [84] Kanonidou, 2020, Polypharmacy in elderly patients with high risk of cardiovascular disease: how is it associated with adherence and health-related quality of life?, Atherosclerosis sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

We carefully considered every one of the included studies and even added two new categories to accommodate for the highly heterogeneous studies included in our analysis.

“However, we carefully considered every one of the included studies and even added two new categories to accommodate for the highly heterogeneous studies included in our analysis.”

Classified as probably not a substantial claim.

Given the high heterogeneity among the studies in our analysis, a structured framework for classifying studies was necessary.

“Furthermore, given the high heterogeneity among the studies in our analysis, a structured framework for classifying studies was necessary.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The need for longer duration studies to demonstrate reductions in cardiovascular risk could explain why too few studies measured clinical outcomes.

“This could be attributed to the need for longer duration studies to demonstrate reductions in cardiovascular risk.”

May combine two claims.

Short-term adherence gains are achievable, but sustaining these improvements over the long term remains challenging.

“This trend indicates that while short-term adherence gains are achievable, sustaining these improvements over the long term remains challenging.”