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

Background: Poor medication adherence to lipid-lowering medications (LLMs) remains a barrier in reducing the burden of cardiovascular disease (CVD). We sought to review interventions aimed at improving adherence to LLMs for the primary or secondary prevention of CVD, and evaluate their effectiveness on patient outcomes. Methods: A systematic review and meta-analysis was performed according to PRISMA guidelines. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, and CINAHL, were searched for studies published between January 1, 2016 and October 3, 2024, reporting randomised controlled trials on interventions to enhance adherence to LLMs. Cochrane's Risk-of-Bias (ROB-2) tool was utilised for quality appraisal. A narrative analysis and a random-effects meta-analysis was conducted, with adherence to LLMs as main outcomes. Pooled effects were calculated using Standardised Mean Difference (SMD) or Odds Ratios (OR). The review's protocol is available on Open Science Framework (https://osf.io/9gx5h). Findings: The systematic review and meta-analysis included 35 and 15 studies, respectively. Participants (n = 51,824) had a mean age ranging 50.2-74.4 years. 6 distinct interventions were employed; most were conducted in primary care settings and employed intensified patient care. Overall, interventions assessed with continuous (SMD 0.17, 95% CI [0.04, 0.31]) and dichotomous (OR 1.26, 95% CI [1.08, 1.47]) measures showed improvements in adherence. Participants who engaged in complex behavioural approaches exhibited improved adherence in dichotomous (OR 1.74, 95% CI [1.17, 2.58]) and continuous outcomes (SMD 0.35, 95% CI [0.15, 0.54]). Pooled estimates suggest no differences in physiological outcomes between the groups. 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". Interpretation: Current interventions bring about improvements in medication adherence, but such improvements are not sustained over the long-term. For real world and practice implications, interventions must be multipronged in nature, addressing a combination of at least two dimensions of medication adherence. Additional global studies, particularly long-term randomised controlled trials, are required to corroborate our findings.