Stroke: lowering cholesterol for secondary prevention
Of the stroke is a dangerous cardiovascular disease and one of the most common causes of death in Germany. Around 270,000 people in Germany suffer from one every year Stroke. Many of them have to reckon with another stroke in the years that follow. One intense LDL cholesterol lowering can save many sufferers from it, as a study now shows. But negative consequences have also been observed.
Almost a fifth of those who suffer a stroke will have a repeat stroke within the next five years. A new meta-analysis published in the journal “JAMA Neurology” with a total of over 20,000 patients confirmed that an intensive lowering of LDL cholesterol protects against recurrent strokes, especially if those affected have vascular calcifications. However, the study also showed that there was slightly more cerebral hemorrhage with this therapy.
In many cases there is a risk of another stroke
As the German Society for Neurology eV (DGN) writes in a current report, strokes are among the most common diseases in Germany with 270,000 cases a year and are associated with a high mortality rate and rate of subsequent disabilities.
They can have different causes, around four out of five strokes are so-called ischemic strokes, in which an area of the brain is no longer (or no longer sufficiently) supplied with blood.
The reason for this is often the severe narrowing or occlusion of a cerebral artery as a result of vascular calcification (atherosclerosis or hardening of the arteries) or a blood clot.
The risk factors that lead to arteriosclerosis, i.e. the formation of plaques (deposits in the vessels) over the course of life, include high blood pressure, smoking, diabetes mellitus, obesity and an increase in LDL cholesterol.
The best prevention of atherosclerotic changes is therefore the treatment or avoidance of such risk factors. Lowering cholesterol in particular plays an important role: an older statin study showed that an LDL cholesterol reduction of 1 mmol/l (39 mg/dl) can reduce the cardiovascular event rate (stroke, heart attack) by around 20 percent.
However, it is unclear whether a more intensive statin-based LDL lowering has a better risk-benefit ratio for the prevention of a subsequent stroke (recurrence) than a less intensive therapy.
Clinical studies of the last 50 years evaluated
The new meta-analysis investigated this question, in which eleven randomized clinical studies from the last 50 years were evaluated in order to compare intensive versus less intensive statin-based LDL-C lowering.
The primary outcome was recurrent stroke, secondary outcome parameters included other severe cardiovascular events and cerebral hemorrhage (hemorrhagic stroke). The final analysis included a total of 20,163 participants (67 percent men, mean age 64.9±3.7 years), the mean follow-up duration was four years.
The mean LDL-C target levels were 79 mg/dl in the group with the more intensive LDL reduction and 119 mg/dl in the patients who had a less intensive LDL reduction.
According to the DGN, the pooled results showed that more intensive LDL-C lowering was associated with a 12 percent reduced risk (RR 0.88) of stroke recurrence (absolute risk 8.1 versus 9.3 percent). The reduction in cardiovascular events was 17 percent and cardiovascular mortality was 8 percent.
In particular, people with evidence of arteriosclerosis benefited significantly (reduction in the risk of recurrence by 21 percent; RR 0.79) from the more intensive treatment, but the effect was not significant in those affected without arteriosclerosis (RR 0.95; p=0.04).
Increased risk of cerebral hemorrhage
Conversely, the more intense LDL-C lowering was associated with a 46 percent increase in the risk of cerebral hemorrhage and a 26 percent increase in the risk of diabetes mellitus (RR 1.26; data from 3/11 studies).
However, the benefits of the statins significantly outweighed the risk of bleeding. Intensive statin treatment prevented 131 ischemic strokes at the expense of 40 intracerebral hemorrhages.
However, the slightly increased risk of bleeding does not appear to be the result of successful LDL-C reduction, but is more likely associated with the slightly anticoagulant properties of statins. This is indicated by a work published in the journal “Circulation”.
In a study published in the journal “Stroke”, which was included in the meta-analysis, low lipid levels were achieved by adding a PSCK inhibitor without increasing the risk of cerebral hemorrhage.
Low LDL cholesterol target
“This meta-analysis supports a low target LDL-C for prevention of recurrence after a first stroke when atherosclerosis is present”explains Prof. Hans Christoph Diener, spokesman for the DGN.
“At the same time, intensified statin therapy seems to be associated with a slightly higher risk of cerebral hemorrhage. Presumably, it makes sense not to max out the statin dose, but instead to use a lipid-lowering combination of statin and ezetimibe to achieve the desired LDL-cholesterol reduction without an increased risk of bleeding.”
The European guidelines on lipid management generally recommend step-by-step therapy, whereby all modifiable lifestyle factors should first be optimized. In the second step, drug treatment with statins is recommended.
If the maximum possible statin dose is not sufficient to lower LDL-C to the target range, ezetimibe should also be given to inhibit cholesterol absorption in the gut. If the LDL cholesterol cannot be lowered to the target range, so-called PCSK9 inhibitors are used according to the GDN.
“In view of the current data, the addition of other substances to the statins should be considered earlier to prevent recurrence after a stroke.”, says the expert. (ad)
Author and source information
This text corresponds to the requirements of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.
- German Society for Neurology eV (DGN): LDL cholesterol reduction for secondary prevention of strokes, (accessed: May 14, 2022), German Society for Neurology eV (DGN)
- Meng Lee, Chun-Yu Cheng, Yi-Ling Wu et al.: Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention: A Meta-analysis of Randomized Clinical Trials; in: JAMA Neurology, (veröffentlicht: 01.04.2022), JAMA Neurology
- Francesco Violi, Camilla Calvieri, Domenico Ferro & Pasquale Pignatelli: Statins as Antithrombotic Drugs; in: Circulation, (veröffentlicht: 15.01.2013), Circulation
- Giugliano RP, Pedersen TR, Saver JL, Sever PS, Keech AC, Bohula EA, Murphy SA, Wasserman SM, Honarpour N, Wang H, Lira Pineda A, Sabatine MS; FOURIER Investigators: Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis; in: Stroke, (veröffentlicht: 21.04.2021), Stroke
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.