Lipid Management
- 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 MACE7‡‡
‡‡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
- Lower LDL-C goals* for patients with ACS1
- Use of PCSK9i to further lower* LDL-C in very high-risk^ patients1##
- 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
Abbreviations
ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CI, confidence interval; CHD, coronary heart disease; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DM, diabetes mellitus; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; eGFR, estimated glomerular filtration rate; FH, familial hypercholesterolaemia; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; LLT, lipid lowering therapy; MACE, major adverse cardiovascular events; MI, myocardial infarction; aOR, adjusted odds ratio; PCSK9, proprotein convertase subtilisin/kexin type 9; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SCORE, systematic coronary risk estimation; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TC: total cholesterol
References
- Mach F, et al. Eur Heart J. 2020;41:111–88.
- Catapano AL, et al. Eur Heart J. 2016;37:2999-3058.
- Ray KK, et al. Eur J Prev Cardiol. 2021;28(11):1279-1289.
- Amput P, et al. Biomed Pharmacother. 2019;109:1171–80.
- Boekholdt M, et al. J Am Coll Cardiol. 2014;64:485-94.
- Brieger D, et al. Med J Aust. 2019;210(2):80–5.
- Schubert J, et al. Eur Heart J. 2021;42:243–252 (and Suppl. Appendix).
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