Dyslipidaemia, and more specifically low-density lipoprotein cholesterol (LDL-C) is one of the primary drivers and a very important modifiable risk factor for atherosclerosis leading to cardiovascular disease (CVD).^1,5,6 

South Africans are at high risk of ASCVD, having amongst the highest prevalence of obesity, undiagnosed diabetes mellitus, smoking and high cholesterol in Africa.7 In a survey that was conducted in rural South Africa, nearly 70% of respondents met the criteria for dyslipidaemia and only 1% were aware that they had abnormal lipid levels.⁴ 

The strongest contributor of total CV risk is age, which can be seen as ‘exposure time’ to risk factors.3 The atherogenic effect of LDL-C appears to be dependent on both the level of circulating LDL-C and the duration of this level. This correlates with data showing that the longer a person is exposed to lower LDL-C levels, the lower the risk of CV events, indicating the earlier treatment is started, the better.^3,6 

A meta-analysis of statins and evidence-based goals of LDL-C showed that with every 1mmol/l reduction in LDL-C level, a 10% reduction in all-cause mortality; 20% reduction in deaths due to coronary heart disease; 24% reduction in major coronary event and a 15% reduction in stroke can be expected.7,11 The Number Needed to Treat (NNT) has been shown to be the lowest in patients with the highest risk at baseline, indicating that those at highest risk are likely to benefit the most from intensive lipid lowering.⁷ 

WHAT IS THE CORRECT LDL-C TARGET FOR YOUR PATIENT? 

Step 1 is to determine the CV risk; likelihood of a person developing an atherosclerotic CV event over a defined period. The higher the risk, the lower the LDL-C target will be.3 Primary CV risk can be calculated by the Framingham risk scoring.7 People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high, or very high risk and therefore do not require scoring.^3,7 

Step 2:  What LDL-C target to aim for? 

> VERY HIGH CV RISK

• LDL-C<1.4mmol/l and  
• >50% reduction in LDL-C from baseline 
• Please note that in patients who experience a second atherosclerotic vascular event within two years (not necessarily the same as the first event) while taking maximum tolerated statin therapy an LDL-C goal of <1mmol/l may be considered 

> High CV risk

• LDL-C<1.8 mmol/l and >50% reduction in LDL-C from baseline 

> Moderate CV risk

• LDL-C< 2.6 mmol/l 

> Low CV risk

• LDL-C<3.0 mmol/l. 

Evidence has shown that lower LDL-C goals are associated with fewer ASCVD events, therefore it is suggested that a minimum reduction of 50% is also necessary in high and very high-risk patients.² 

Step 3 is to select the optimal treatment; after lifestyle modifications, the use of high-intensity statins (Atorvastatin/Rosuvastatin) remains the recommended first line agents for maximum LDL-C reduction, titrated up if needed, followed by adding azetimibe and thereafter a PCSK9-inhibitor.3,7 The %LDL-C reduction that can be expected from a statin is 30%-50%, with a further 15% reduction when adding Ezetimibe. A proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9-I) significantly reduce LDL-C by 60% (85% in combination with statin and ezetimibe.)³ 

Early diagnosis, lifestyle modification and aggressive management of CV risk factors are critical to prevent an epidemic of CVD in South Africa.1,7 Aim and hit the recommended LDL-C targets – the lower, the better.^2,3,9,11  

For more information, please contact za.mslondemand@sanofi.com 

MAT-ZA-2200610-07/2022-2.0  

REFERENCES:  

1. Libby, P. and Tokgözoğlu, L. (2022). Chasing LDL cholesterol to the bottom — PCSK9 in perspective. Nature Cardiovascular Research, 1(6), pp.554–561. doi:10.1038/s44161-022-00085-x. 
2. Klug, E.Q. and Raal, F.J. (2020). New cholesterol targets for patients at high or very high cardiovascular risk and the indications for PCSK9 inhibitors. South African Medical Journal, 110(11), p.1059. doi:10.7196/samj.2020.v110i11.15191.
3. Mach, F., Baigent, C., Catapano, A.L., Koskinas, K., Casula, M., Badimon, L., Chapman, J., De Backer, G.G., Delgado, V., Ference, B., Graham, I., Halliday, A., Landmesser, U., Mihaylova, B., Pederson, T., Riccardi, G., Richter, D., Sabatine, M., Taskinen, M.-R. and Tokgozoglu, L. (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal, 41, pp.111–188.
4. Reiger, S., Jardim, T., Abrahams-Gessel, S., Crowther, N., Wade, A., Gomez-Olive, F., Salomon, J., Tollman, S. and Gaziano, T., 2017. Awareness, treatment, and control of dyslipidemia in rural South Africa: The HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) study. PLOS ONE, 12(10), p.e0187347.
5. Masilela, C., Adeniyi, O.V. and Benjeddou, M. (2022). Prevalence, patterns and determinants of dyslipidaemia among South African adults with comorbidities. Scientific Reports, 12(1). doi:10.1038/s41598-021-04150-6.
6. Braunwald, E. (2021). How to live to 100 before developing clinical coronary artery disease: a suggestion. European Heart Journal, 43(4), pp.249–250. doi:10.1093/eurheartj/ehab532.
7. Klug, E.Q., Raal, F.J., Marais, A.D., Smuts, C.M., Shamroth, C., Jankelow, D., Blom, D.J. and Webb, D.A. (2018). Klug E, Raal FJ, Marais AD, et al. South African Dyslipidaemia Guideline Consensus Statement 2018 Update: A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). S Afr Med J 2018;108(11b):973-1000. South African Medical Journal, 108(11), pp.973–1000. doi:10.7196/samj.2018.v108i11.13383. 
8. Heartfoundation.co.za. 2022. CVD-stats-Reference-document-2016. [online] Available at: <https://www.heartfoundation.co.za/wp-content/uploads/2017/10/CVD-Stats-Reference-Document-2016-FOR-MEDIA-1.pdf> [Accessed 4 August 2022].
9. Khan, S.U., Khan, M.U., Virani, S.S., Khan, M.S., Khan, M.Z., Rashid, M., Kalra, A., Alkhouli, M., Blaha, M.J., Blumenthal, R.S. and Michos, E.D. (2020). Efficacy and Safety for the Achievement of Guideline-Recommended Lower Low-Density Lipoprotein Cholesterol Levels: A Systematic Review and Meta-Analysis. American Journal of Preventive Cardiology, 3, p.100050. doi:10.1016/j.ajpc.2020.100050.
10. Giugliano, R. (2017). Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with PCSK9 inhibitor evolocumab: a prespecified secondary anaylysis of the FOURIER trial. Lancet, 390(10106), pp.1962–1971.
11. Soran, H., Dent, R. and Durrington, P. (2017). Evidence-based goals in LDL-C reduction. Clinical Research in Cardiology, 106(4), pp.237–248. doi:10.1007/s00392-016-1069-7.