During this year’s “Stroke Summer School 2021” in Basel, Switzerland, Gian Marco De Marchis (Stroke Unit, University Hospital Basel, Switzerland) provided an overview of the most important recent findings regarding lipids and stroke.

Lipid target levels decisive of cardiovascular risk in stroke patients

Dr De Marchis dived into the topic by presenting an interesting double-blinded clinical study published last year. Researchers investigated cardiovascular events in patients with an ischemic stroke with associated atherosclerosis depending on low-density lipoprotein (LDL) target levels.¹ It was demonstrated that patients with a target LDL level of less than 1.8 mml/L had a lower risk of subsequent cardiovascular events than patients with a higher LDL target range of 2.3–2.8 mmol/L. Per LDL cholesterol decrease of 1 mmol/L, the study group reported a 20% decrease in cardiovascular events.¹ Dr De Marchis noted that the current European guidelines for the management of dyslipidaemias also follow the concept “the lower, the better”.²

How to reach low target LDL levels

“How can we reach these ambitious LDL target levels?”, Dr De Marchis asked during his presentation. The answer is high-intensity statins, that allow an LDL reduction of at least 50%. However, for patients with high baseline LDL levels above 2.8 mmol/L statins alone will not suffice.

Combination therapies with statins potentially lower LDL levels further

Dr De Marchis continued his presentation discussing options for patients with high baseline LDL levels. One therapy option in combination with statins is ezetimibe. Ezetimibe inhibits the uptake of cholesterol in the intestine, leading to lower LDL levels in the bloodstream.³ It was shown in two studies that ezetimibe can reduce stroke risk in combination with high-intensity statins.^4,5 “What else is new?”, Dr De Marchis asked. He went on to speak about another potential combination therapy, namely bempedoic acid, that inhibits the synthesis of cholesterol. It has been previously shown to reduce LDL levels by 16.5%, but the results of the large CLEAR outcomes trial investigating bempedoic acid are expected earliest in 2022.⁶ Proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis inhibitors are another LDL level decreasing therapy option mentioned by Dr De Marchis. Inclisiran, a small interfering RNA molecule, is one example of a PCSK9 inhibitor.⁷ It decreased LDL levels by more than 45% in two phase 3 clinical trials and only needs to be administrated every 6 months subcutaneously, making it an interesting treatment option for patients.⁷

What else to consider in the lipid diagnosis?

To wrap up his talk, Dr De Marchis spoke about important things to consider in the lipid diagnostic besides LDL levels. There is a vast range of atherogenic lipoproteins that also contain cholesterol.⁸ Measuring LDL levels only – especially in patients with metabolic syndromes – can be misleading in terms of the actual presence of cholesterol. Therefore, according to the European guideline committee, the levels of apolipoprotein B (ApoB), the protein that surrounds all types of atherogenic lipoproteins, should also be analysed for cardiovascular risk assessment.² Furthermore, especially lipoprotein A (LPA) has lately received attention, as a study group from Zürich was able to show that elevated LPA levels are associated with increased risk for recurrent cerebrovascular events.⁹ “There are no specific therapies available right now that allow a reduction of LPA,” Dr De Marchis concluded. However, measuring LPA levels in patients would still be important to evaluate risk and to consider new or alternative treatment approaches.

References

1. Amarenco P et al. N Engl J Med. 2020;382:9–19
2. Mach F et al. Eur Heart J. 2020;41:111–88
3. Ibanez B et al. Future Lipidology. 2006;1:255–66
4. Cannon CP et al. NEJM. 2015;372:2387–97
5. Bohula EA et al. Circulation. 2017;136:2440–50
6. Ray KK et al. NEJM. 2019;380:1022–32
7. Ray KK et al. NEJM. 2017;376:1430–40
8. Sniderman et al. JAMA Cardiol. 2019;4:1287–95
9. Arnold M et al. Eur Heart. 2021;42:2186–96