Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
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2022-05-23
Published articles
Journal：CNS Neuroscience & Therapeutics
Publication type: Original Contributions
IF(IF): 7.035
PMID: 35603937 Link To Pubmed Full text Download
Background And Purpose
Statins could decrease serum lipid level and stabilize the atherosclerotic plaque to reduce the risk of recurrence of ischemic stroke. Spontaneous intracerebral hemorrhage (ICH) has different pathological and pathophysiological mechanisms compared with ischemic stroke and it remains a debate whether statins treatment would decrease risk of ICH. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed more ICH in patients treated with statins. [1] This effect could be influenced by history of cerebrovascular disease and different lipid levels. [2-4] However, statins treatment is also proved to have potential effects including endothelial stabilization, antithrombotic properties, anti-inflammatory actions, and up regulation of endothelial nitric oxide synthase. [5] A nationwide case–control study that included 7696 cases of ICH and 14 670 controls reported a reduced incident ICH among statin-treated patients. [6] Several cohort studies revealed that, for patients diagnosed with ICH, statins could reduce the mortality and disability, indicating better clinical outcomes. [7,8] Hence, to clarify the effect of statins treatment on ICH, particularly outcomes of ICH, is crucial. In the current study, we compare the in-hospital mortality and the percentage of the evacuation of intracranial hematoma between prior statin users and non-users to investigate the impact of prior statin treatment on ICH. Moreover, we conducted additional analysis to investigate the effect of prior statin treatment on ICH in particular groups including patients with a history of stroke, patients with a history of dyslipidemia and patients with different serum lipid levels.
Method
To compare the in-hospital mortality and percentage of the evacuation of intracranial hematoma between the patients with prior statin therapy or not before spontaneous intracerebral hemorrhage (ICH) events. Statistical analysis Continuous variables will be expressed as mean± SD for normally distributed data and median [interquartile range] for non-normally distributed data. Categorical variables will be expressed as number (percentage). Table 1 In univariate analyses, to compare the baseline characteristics between prior statin users and non-users, normally distributed data will be compared using the Student’s t test and non-normally distributed data will be compared using Mann-Whitney U test. Categorical variables will be compared using Pearson χ2 or Fisher exact test, as appropriate. Additional univariate analyses will be conducted to compare the baseline characteristics between dead patients and survivors, and between the patients with operation or not. A multiple logistic regression analysis will be used to determine the independent predictors of the in-hospital mortality. All covariates with a P value ≤0.15 in the comparison of baseline characteristics and prior statin use between the dead patients and survivors will enter into the multiple logistic regression. ORs and 95% CIs will be recommended to be presented in forest plots. Figure 1 After the univariate analysis between the patients with operation or not, another multiple logistic regression analysis will be used to determine the independent predictors of the percentage of the evacuation of intracranial hematoma. Figure 2 A propensity score match (PSM) will be used to balance the baseline characteristics between prior statin users and non-users. Table 2 Another two logistic regression will be conducted to determine whether prior statin use is a predictor of in-hospital mortality and the percentage of the evacuation of intracranial hematoma respectively. Analyses stratified by low density lipoprotein cholesterol (LDL-C) levels will be conducted to investigate the impact of prior statin use on in-hospital mortality and percentage of the evacuation of intracranial hematoma respectively in patients with different LDL-C levels, presented with ORs and 95% CIs, and forest plots. Figure 3 The cut-off value of LDL-C levels will be set at 1.8mmol/L and 2.6mmol/L (≤1.8mmol/L, ＞1.8mmol/L and ≤2.6mmol/L, ＞2.6mmol/L), based on the 2019 ESC recommendation. Subgroup analyses will be conducted in patients with history of stroke, history of ischemic stroke, and history of hemorrhagic stroke to determine the impact of prior statin use on in-hospital mortality and percentage of the evacuation of intracranial hematoma respectively. Figure 4 A sensitivity analysis will be performed in patients with history of dyslipidemia to investigate the impact of prior statin use on in-hospital mortality and the percentage of the evacuation of intracranial hematoma respectively. Figure 5
Conclusion
Prior statin use was not associated with in-hospital mortality but did reduce evacuation of intracranial hematoma rates.
Main results
The final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in-hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61-1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61-0.82). Propensity score matching analyses yielded similar results.