High Dose Statins Mey Improve Recovery in Stroke: Study

Recent research published in Neurology India suggests  that serum cholesterol levels were inversely related to the stroke severity, but a higher the dose of statins resulted in better functional outcome and survival in post-stroke patients, possibly due to its neuroprotective effect.

Stroke is one of the leading causes of mortality and morbidity, and more than half of stroke survivors have residual deficits and are left with permanent disabilities, making them dependent on others for activities of daily living. Due to improved healthcare facility and knowledge, there is increase in the post-stroke survival.

Studies have shown that lower cholesterol levels are consistently been found to be strongly associated with lower risks of coronary artery diseases but not with lower risks of stroke. However, the use of statins for secondary prevention of stroke is well established and previous studies support this. Few studies have shown possible neuroprotective effects of statins. The neuroprotective property may enhance the recovery of central nervous system post stroke. The recommended dosage of statins post stroke is not clearly defined. But, few studies have concluded higher dose of statins is associated with reduction in recurrence rate of major stroke and better functional outcome. Pharmacokinetic studies have suggested that Indians achieve higher levels of circulating statins compared to the Caucasian population when administered comparable doses.The higher doses of statins equivalent to atorvastatin 80 mg is mostly not well tolerable in Indian population, due to increased side effects, leading to discontinuation of treatment.

Shridharan et al conducted a study to see the effect of serum cholesterol levels on severity of stroke measured by the infarct volume, and assess the effect of dosage of statins on functional outcome following acute ischemic stroke in Indian population.The authors evaluated the relation between serum cholesterol levels and severity of stroke by comparing the mean cholesterol levels with infarct volume. It was also evaluated whether the dosage of statin has prognostic value by comparing the functional outcome at 3 months with the patient's statin dose.

Of the 100 patients admitted with acute ischemic stroke in anterior circulation with hemiplegic upper limb power of at least MRC ≤3, number of males were 60%, mostly belonged to 60-79 years of age. Hypertension was present in 52% of patients and 32% had cardiac co-morbidity, and 11% patients had atrial fibrillation.

They found that hypercholesterolemia—>200 mg/dl  was present in 65 patients, cholesterol level of >250 mg/dl (>6.46 mmol/L) was present in 25 patients. They also measured the infarct volume and correlated with the serum cholesterol level. The results showed an inverse relation; with higher infarct volume having low mean cholesterol levels and vice versa. This showed that higher cholesterol level favored development of minor stroke and the post-stroke mortality was inversely related to the total cholesterol. This was explained by higher cholesterol levels that favored the development of small-vessel disease and thereby less severe stroke and associated lower mortality. 

High-dose statins are advised post stroke, even if the baseline lipid profile is within normal limits. The use of high-dose statins is always limited by tolerability, especially in Indian population. In routine practice, we often come across statin dose in post stroke patients varying between 10 and 40 mg Atorvastatin (or equivalent dosage). The authors evaluated the effects of dose of statins post stroke and functional outcome at 90 days. They compared (modified Rankin Score) mRS at day 7 and day 90 with dose of statins (high dose vs. low dose) and mean difference of mRS between day 7 and day 90 between these two groups. There was no statistically significant difference of mRS between the high dose and low dose at day 7 and day 90. However, when we compared the mean fall in mRS between high dose versus low dose from day 7 to day 90, there was statistically significant fall of mRS in patients taking high dose of statins, suggesting a significantly improved functional outcome in high-dose statin groups

The result of our study can be explained by effect of statins on inhibition of inflammatory activation during the acute phase, immunomodulation, endothelial function-enhancing effects in addition to lipid lowering effect. Neuroprotection and regenerative effect of statin may also explain improved functional outcome of stroke patients on high-dose statins.:, say the authors.

The study concludes that  serum cholesterol levels are inversely related to the stroke severity. Statins are beneficial in stroke patients; a higher dosage is associated with better functional outcome and survival. The effect is probably not related to statin's lipid lowering property but related to its neuroprotective effects and anti-inflammatory property. Large randomized controlled trials are required to prove the dosage for acute ischemic stroke in consideration with stroke subtypes, ethnicity, and other medical co-morbidities.

Reference:

Shridharan P, Nair R, Gorthi SP, Prakashini K, Chatterjee A. Effects of Serum Cholesterol on Severity of Stroke and Dosage of Statins on Functional Outcome in Acute Ischemic Stroke. Neurol India 2023;71:923-7DOI: 10.4103/0028-3886.388115