From the Guidelines
The current NICE guidelines for lipid management should prioritize a systematic approach to cardiovascular disease (CVD) prevention through risk assessment and targeted interventions, with a focus on upfront lipid-lowering combination therapy for very high-risk secondary prevention patients, as recommended by the 2024 International Lipid Expert Panel (ILEP) position paper 1.
Key Recommendations
- For very high-risk secondary prevention patients, upfront lipid-lowering combination therapy, including double or triple therapy in the case of extremely high-CVD-risk patients, should be considered to increase the effectiveness of therapy and reduce the risk of recurrent CVD events and mortality 1.
- In addition to statins and ezetimibe, bempedoic acid and monoclonal antibody/small interference RNA (siRNA) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) can be used to significantly reduce LDL-C levels and consequently reduce the risk of ASCVD, particularly in patients with familial hypercholesterolaemia (FH), those with an ASCVD pre-event, and those who have already experienced an acute coronary syndrome (ACS) 1.
- The use of new agents, such as PCSK9 inhibitors, should be prioritized for patients who are most likely to benefit from them, taking into account their high cost and potential benefits in reducing LDL-C levels and ASCVD risk 1.
- Healthcare providers should emphasize the importance of adherence to medication and lifestyle modifications, including diet, exercise, smoking cessation, and moderate alcohol consumption, to maximize cardiovascular risk reduction 1.
Rationale
- The 2024 ILEP position paper provides updated guidance on the optimal use of lipid-lowering therapy in established atherosclerotic cardiovascular disease and following acute coronary syndromes, highlighting the need for more effective therapy in very high-risk secondary prevention patients 1.
- The paper emphasizes the importance of upfront combination therapy in patients with established pre-event atherosclerotic CVD and in specific populations of patients with metabolic disorders and statin intolerance 1.
- The use of lipid-lowering therapy, particularly statins, has been shown to reduce the risk of ASCVD events and mortality, and the 2024 ILEP position paper provides guidance on how to optimize therapy in very high-risk patients 1.
From the Research
Current NICE Guidelines for Lipids Management
The current guidelines for lipids management in the population are based on reducing cardiovascular morbidity and mortality by lowering low-density lipoprotein cholesterol (LDL-C) levels with statins as the primary goal of therapy 2.
Primary and Secondary Prevention
- For secondary prevention patients, those with coronary heart disease (CHD) or CHD risk equivalents, intensive LDL-C lowering is recommended 2.
- For primary prevention, reduction in LDL-C levels is based on patient risk for CHD 2.
- Statins benefit those who are at moderate to high risk and appear to have less clinical benefit for those at low risk 2.
Treatment Targets and Therapies
- Secondary targets have been proposed to decrease residual risk for CHD events in high-risk patients, including non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and apolipoprotein B 2.
- Combination therapy with other agents, such as PCSK9 inhibitors, is a safe, effective, and optimal therapeutic approach for many high-risk patients 3.
- PCSK9 inhibitors can reduce LDL-C by 50-60% above that achieved by statin therapy alone and may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 3.
- Other lipid-lowering therapies, such as fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, and omega-3 fatty acids, may also be used to manage lipids 4, 5, 6.
Safety and Efficacy
- Combination therapy with statins and omega-3 fatty acids was generally more effective on lipid concentration than statin monotherapy, but with some safety issues associated with their concomitant use 5.
- The cost-effectiveness of PCSK9i therapy is limited to secondary prevention in high-risk patients 3.