Lipid Management

Cardiovascular

• 2019 ESC/EAS dyslipidaemia guidelines propose a CV risk-based approach and recommend lower LDL-C goals*, which are especially relevant to high- and very high-risk patients.¹

*The 2019 ESC/EAS LDL-C goal for very high-risk people is <1.4 mmol/L and ≥50% reduction from baseline.1 2016/2019 risk-based LDL-C targets for very high CV risk patients: 2016, <1.8 mmol/L; 2019, <1.4 mmol/L.^1,2

• However, in clinical practice, many are not achieving the recommended LDL-C goal of <1.4 mmol/L (55 mg/dL), despite receiving moderate- or high-intensity statin monotherapy, therefore a shift towards additional lipid-lowering therapy is required.³
• Lowering LDL-C levels can help with improved lipid metabolism and reduce plasma LDL-C, leading to reduced risk of atherosclerosis.⁴
• PCSK9 inhibition offers an additional strategy to help reach LDL-C goals*, and is guideline-recommended for post-acute coronary syndrome (ACS) patients on top of statins and ezetimibe (Class 1A)†¹

^†For secondary prevention in patients at very-high risk not achieving their LDL-C goal on a maximum tolerated dose of a statin and ezetimibe, a combination with a PCSK9 inhibitor is recommended.¹ For definition of very high-risk, refer to ESC/EAS Dyslipidaemia Guidelines. 

This page summarises important information on lipid management and recommendations for lowering LDL-C.

The role of low-density lipoprotein cholesterol for cardiovascular disease

Cardiovascular disease is a major cause of mortality worldwide.⁴

Coronary heart disease (CHD) is common in cardiovascular patients and there are many CHD risk factors that can contribute to atherosclerosis, including high blood cholesterol and triglycerides levels.⁴

• LDL-C is a well-established risk factor for cardiovascular disease. High circulating PCSK9 levels can increase circulating LDL-C and can contribute to atherosclerosis.⁴
• Residual cardiovascular risk post-Acute Coronary Syndrome (ACS) is also directly related to residual LDL-C levels.⁵

Real-world evidence on reaching LDL-C lowering goals

Among 5,888 patients enrolled (3,000 primary and 2,888 secondary prevention) only 22% of very high risk patients on high-intensity statin monotherapy achieved the lower 2019 ESC/EAS guidelines goal of <1.4 mmol/L (vs 2016 goal of <1.8mmol/L).³ 2019 goal attainment is a post-hoc analysis in the DA VINCI study.

2016 and 2019 ESC/EAS LDL-C goal attainment in very high-risk patients with established ASCVD, by LLT received (n=2,039)

#2016/2019 risk-based LDL-C targets for very high CV risk patients: 2016, <1.8 mmol/L; 2019, <1.4 mmol/L.³

§PCSK9i in combination with statins and/or ezetimibe

An 18-country, cross-sectional, observational study in 5,888 patients prescribed lipid lowering therapy (LLT) for primary or secondary prevention between June 2017 and November 2018. Primary outcome was the achievement of risk-based 2016 ESC/EAS LDL-C goal while receiving stabilised LLT; 2019 goal achievement was also assessed. A post-hoc analysis determined the goal achievement according to the 2019 goals.

^2019 ESC/EAS guidelines defines very high risk as people with any of the following: 

• Documented atherosclerotic cardiovascular disease (ASCVD), either clinical or unequivocal on imaging;
• Diabetes mellitus (DM) with target organ damage (microalbuminuria, retinopathy, or neuropathy) or at least three major risk factors; or early onset of Type 1 DM of long duration (>20 years); 
• Severe chronic kidney disease (CKD) (eGFR <30 mL/min/1.73 m2);
• A calculated SCORE ≥10% for 10-year risk of fatal cardiovascular disease (CVD);
• Familial hypercholesterolaemia (FH) with ASCVD or with another major risk factor.

Only ~55% of patients in Australia receive guideline-recommended intensive lipid-lowering^§ therapy at 6 or 12 months after an ACS event  ^6¶

• Not receiving intensive lipid-lowering therapy is strongly linked with not being prescribed at the time of hospital discharge (aOR 7.24 [95% CI 4.37–12.0]).⁶
• Optimising oral lipid-lowering therapy for patients with prior ACS may help prevent recurrent coronary events for those at high risk.⁶

¶Australian patients enrolled in the CONCORDANCE registry (n=3,441) between January 2015 to May 2016 for whom information on lipid-lowering therapy 6 or 12 months after discharge from hospital were available. §Intensive lipid-lowering therapy defined as atorvastatin (≥40 mg/day), rosuvastatin (≥20 mg/day), or simvastatin** (≥80 mg/day), with or without ezetimibe; lower intensity statin therapy with ezetimibe; or ezetimibe alone.⁶

**Doses of simvastatin >80 mg/day are not currently approved in Australia.

The benefits of early initiation for LDL-C lowering therapy

Greater early^†† LDL-C lowering with statins after myocardial infarction can reduce the risk of recurrent MACE^7‡‡

^‡‡Patients who achieved a greater early†† LDL-C reduction from baseline with statin therapy (>1.85 mmol/L) had a 23% RRR in MACE outcomes vs. patients with smaller LDL-C reductions from baseline (<0.36 mmol/L); HR: 0.77 (95% CI 0.70–0.84); P-value not reported.⁷

A prospective, observational study in 40,607 myocardial infarction (MI) patients.⁷ Hazard ratio (HR) for the composite outcome MACE by change in low-density lipoprotein cholesterol (LDL-C mmol/L) from index event to cardiac rehabilitation visit, adjusted for clinical characteristics, and established cardiovascular risk factors. Solid line: hazard ratio (HR) with 95% confidence interval (CI), shadowed area, in relation to low-density lipoprotein cholesterol change using restricted cubic splines with four knots. Vertical dotted lines: percentiles. X-axis presented on a linear scale. Population distribution in relation to change in low-density lipoprotein cholesterol below spline. ^††Defined as LDL-C reduction achieved between index MI event and the cardiac rehabilitation visit (6–10 weeks after discharge).⁷ ^^MACE: major adverse cardiovascular event (composite outcome of CV mortality, MI, and ischaemic stroke).

What are the treatment goals for LDL-C?

The 2019 ESC/EAS dyslipidaemia guidelines propose a CV risk-based approach and recommend lower LDL-C goals*, which are especially relevant to high- and very high-risk patients.¹

*The 2019 ESC/EAS LDL-C goal for very high-risk people is <1.4 mmol/L and ≥50% reduction from baseline.1 2016/2019 risk-based LDL-C targets for very high CV risk patients: 2016, <1.8 mmol/L; 2019, <1.4 mmol/L.^1,2

1. Lower LDL-C goals* for patients with ACS¹
2. Use of PCSK9i to further lower* LDL-C in very high-risk^ patients^1##
3. Early^¶¶ use of PCSK9i after an ACS event¹

Three major changes in the recommendations for lipid management

*The 2019 ESC/EAS LDL-C goal for very high-risk people is <1.4 mmol/L and ≥50% reduction from baseline.1 2016/2019 risk-based LDL-C targets for very high CV risk patients: 2016, <1.8 mmol/L; 2019, <1.4 mmol/L.^1,2

^2019 ESC/EAS guidelines defines very high risk as people with any of the following:

Documented atherosclerotic cardiovascular disease (ASCVD), either clinical or unequivocal on imaging; Diabetes mellitus (DM) with target organ damage (microalbuminuria, retinopathy, or neuropathy) or at least three major risk factors; or early onset of Type 1 DM of long duration (>20 years); Severe chronic kidney disease (CKD) (eGFR <30 mL/min/1.73 m2); A calculated SCORE ≥10% for 10-year risk of fatal cardiovascular disease (CVD); familial hypercholesterolaemia (FH) with ASCVD or with another major risk factor.

^##Adding a PCSK9i to maximally tolerated statins and ezetimibe is recommended by the 2019 ESC/EAS guidelines.^1§§

^§§In secondary prevention for patients at very high risk not achieving their goal on a maximum tolerated statin and ezetimibe, a combination with a PCSK9 is recommended. In very high-risk FH patients (with ASCVD or another major risk factor) who do not achieve their goal on a maximum tolerated statin and ezetimibe, a combination with a PCSK9i is recommended.¹

^¶¶Early after the event (if possible, during hospital or after 4-6 weeks despite maximally tolerated statins and ezetimibe).¹

Treatment algorithm for pharmacological LDL-C lowering