Achievement of lipid modification goals with Statins & Ezetimibe

• This review highlighted that a significant proportion of UK patients with CVD have sub-optimal reductions in cholesterol/non-high-density lipoprotein cholesterol (HDL-C)/ low-density lipoprotein cholesterol (LDL-C) despite the widespread availability of lipid-lowering therapy and guidance.
• Reasons for sub-optimal lipid lowering are multifactorial, including a lack of compliance with guidelines, patient adherence, statin intolerance, and statin reluctance as well as wider genetic factors.
• Possible strategies that improve current lipid management and attainment of lipid-lowering goals include:
  • Improving the patient–healthcare professional partnership; conducting audits of local prescribing versus guidance; implementing plans for the refinement of current services; considering alternative options that improve adherence (cost-effective single-pill combinations)
• Additional options are needed in patients at a high risk of CVD events, in whom lipid-lowering goals are not achieved with statins and ezetimibe alone.

• Despite accepting LDL-C as a causal cardiovascular risk factor and thus a critical component in CVD risk reduction, lipid lowering is not adequately attained in the UK.
• This review was conducted to understand current UK lipid management guidance in relation to treatment with statins and ezetimibe and the corresponding attainment of recommended lipid-lowering goals, with a focus on publications between January 2017 and February 2020.

Identified publications were reviewed against lipid management guidelines in relation to CVD risk from National Institute for Health and Care Excellence (NICE, CG181), Scottish Intercollegiate Guidelines Network (SIGN, 149), and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS).

Lipid management in the UK:

• NICE CG181 (updated in 2016) and SIGN 149 (2017) are the main clinical guidelines for lipid management in relation to cardiovascular risk in the UK.
• Current UK guidelines advise that lipid-lowering therapy should be considered for both the primary and secondary prevention of CVD based on CVD risk assessment (10 year) in addition to recommending lifestyle modifications.
• Although a range of lipid-modifying therapies are approved in the UK, statins are the mainstay of initial recommended treatment strategies.
• NICE and SIGN guidance recommend that lipid-lowering therapy should achieve >40% reduction in non-HDL-C at 3 months.
• ESC/EAS guidelines highlight lowering LDL-C and total cholesterol as the primary target of therapy.
• LDL-C measurement remains relevant in routine clinical practice as the guidance for later lines of therapy (post-statin) is predicated on the evaluation of LDL-C levels.
• NICE states that ezetimibe should be considered in combination with statin for primary hypercholesterolemia when total cholesterol or LDL-C is not adequately controlled after initial statin therapy.
• Alternative therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab or alirocumab may be considered for certain patients with hypercholesterolemia or mixed dyslipidemia who have a high or very high risk of CVD, but only if LDL-C levels are persistently above recommended thresholds.
• Recent ESC/EAS guidelines also state that if patients fail to achieve LDL-C goal within 4–6 weeks despite lifestyle modifications and maximally tolerated highintensity statins, add-on therapy with ezetimibe and subsequently a PCSK9 inhibitor should be considered.

Sub-optimal achievement of guideline-derived lipid modification goals:

• Several large UK studies highlighted that a significant proportion of patients are not being adequately managed according to best practice guidelines despite widespread availability and supporting evidence on the effectiveness of statins and combination therapy with ezetimibe.
• Variations in individual patient genotypes, statin intolerance, patient adherence, and the potency of statin prescribing might be reasons for sub-optimal LDL-C reductions.
• Limited prescribing of combination therapy may also contribute to sub-optimal lipid lowering.
• Other factors likely to contribute to sub-optimal lipid lowering include late intervention in the disease trajectory, a lack of follow-up and treatment adaptation according to risk factors or fulfillment of therapeutic goals, and statin intolerance.
• Misconceptions about statin intolerance and statin-related adverse events may lead to a reluctance to take statins and early discontinuation and/or non-adherence, which may result in inadequate lipid lowering.

Possible strategies that improve current lipid management include*:

• Measures for improving the patient–healthcare professional partnership; conducting audits of local prescribing versus guidance; implementing plans for the refinement of current services; follow-up and monitoring procedures for different types of therapy; and considering alternative options that improve treatment adherence (cost-effective single pill)

Additional information:

• Possible strategies that improve adherence with cholesterol goals*