Proportion of High-Risk/Very High-Risk Patients in Europe with Low-Density Lipoprotein Cholesterol at Target According to European Guidelines: A Systematic Review

Abstract

Objective: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines.

Design: Systematic literature review.

Data sources: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature.

Eligibility criteria: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]).

Data extraction and synthesis: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test.

Results: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only).

Conclusions: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase.

Protocol registration: PROSPERO registration number; CRD77844.

Keywords: Cardiovascular disease; Guidelines; High-risk; LDL-C targets; Low-density lipoprotein cholesterol; Systematic review.

Fig. 1

PRISMA flow diagram. ^aFor the secondary outcome a meaningful comparison was only possible among studies reporting on individuals with established CVD. CINAHL Cumulative Index to Nursing and Allied Health Literature, CVD cardiovascular disease, FH familial hypercholesterolaemia, LDL-C low-density lipoprotein cholesterol, RCT randomised controlled trial, SCORE Systematic Coronary Risk Evaluation

Fig. 2

LDL-C goal achievement among patients with SCORE 5–10% (high risk) and SCORE ≥ 10% (very high risk). Studies included in this figure were those reporting LDL-C goal achievement stratified by high risk and very high risk [–51]. LDL-C low-density lipoprotein cholesterol, HR high risk, VHR very high risk