Marvardi Michele, Paciaroni Maurizio, Caso Valeria
Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Clinical Neurology Unit, Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.
Eur Stroke J. 2025 Jan 9:23969873241307520. doi: 10.1177/23969873241307520.
The efficacy and safety of statins for secondary prevention in patients who have experienced a cardioembolic stroke are not well-defined. However, previous observational data reported hyperlipidemia as a risk factor for both ischemic and bleeding complications in patients with AF and previous stroke. Based on these premises, we conducted a sub-analysis of the RAF and RAF-NOAC studies to evaluate the efficacy and safety of statins in secondary prevention in patients with acute ischemic stroke and AF.
We combined patient data from the RAF and RAF-NOAC studies, prospective observational studies conducted across Stroke Units in Europe, the United States, and Asia from January 2012 to June 2016. We included consecutive patients with AF who suffered an acute ischemic stroke with a follow-up of 90 days. Our outcomes were the combined endpoint, including stroke, transient ischemic attack, systemic embolism, symptomatic intracerebral hemorrhage, and major extracranial bleeding. Furthermore, both ischemic and hemorrhagic outcomes were evaluated separately.
A total of 1742 patients were included (46% male), and 898 (52%) received statins after the index event, of whom 436 (48.6%) were already taking statins before the index event, 462 (51.4%) started treatment after. At multivariable analysis, statin use was statistically associated with age (OR 0.92, 95% CI 0.97-0.99, = 0.001), male sex (OR 1.35, 95% CI 1.07-1.70, = 0.013), anticoagulation (OR 2.53, 95% CI 1.90-3.36, < 0.0001), hyperlipidemia (OR 5.52, 95% CI 4.28-7.12, < 0.0001), paroxysmal AF (OR 1.40, 95% CI 1.12-1.75, = 0.003), leukoaraiosis (OR 1.39, 95% CI 1.11-1.75, = 0.004) and heart failure (OR 0.72, 95% CI 0.53-0.98, = 0.034). Statin use was not associated with the combined outcome event (OR 0.84, 95% CI 0.58-1.23, = 0.3) and ischemic outcome event (OR 1.17, 95% CI 0.73-1.88, = 0.5) while was associated with a lower risk of hemorrhagic outcome event (OR 0.51, 95% CI 0.28-0.91, = 0.02).
Statins protect cerebral arterial vessels (particularly small vessels) from subacute damage due to hypertension, diabetes, and other harmful agents (such as reactive oxygen species, proinflammatory cytokines, etc.) due to their systemic anti-inflammatory and endothelium-protective effects.
Our data show that statins seem to protect against global bleeding events in cardioembolic stroke patients; this may be due to the pleiotropic effect of statins. More data are warranted to confirm these findings.
他汀类药物在经历心源性栓塞性卒中患者二级预防中的疗效和安全性尚未明确界定。然而，既往观察性数据报道高脂血症是房颤和既往卒中患者缺血性及出血性并发症的危险因素。基于这些前提，我们对RAF和RAF-NOAC研究进行了亚组分析，以评估他汀类药物在急性缺血性卒中和房颤患者二级预防中的疗效和安全性。
我们合并了RAF和RAF-NOAC研究的患者数据，这两项研究是2012年1月至2016年6月在欧洲、美国和亚洲的卒中单元进行的前瞻性观察性研究。我们纳入了连续发生急性缺血性卒中且随访90天的房颤患者。我们的结局是复合终点，包括卒中、短暂性脑缺血发作、系统性栓塞、症状性脑出血和颅外大出血。此外，分别对缺血性和出血性结局进行了评估。
共纳入1742例患者（46%为男性），898例（52%）在索引事件后接受了他汀类药物治疗，其中436例（48.6%）在索引事件前已服用他汀类药物，462例（51.4%）在索引事件后开始治疗。在多变量分析中，他汀类药物的使用与年龄（比值比0.92，95%置信区间0.97 - 0.99，P = 0.001）、男性（比值比1.35，95%置信区间1.07 - 1.70，P = 0.013）、抗凝治疗（比值比2.53，95%置信区间1.90 - 3.36，P < 0.0001）、高脂血症（比值比5.52，95%置信区间4.28 - 7.12，P < 0.0001）、阵发性房颤（比值比1.40，95%置信区间1.12 - 1.75，P = 0.003）、脑白质疏松（比值比1.39，95%置信区间1.11 - 1.75，P = 0.004）和心力衰竭（比值比0.72，95%置信区间0.53 - 0.98，P = 0.034）具有统计学关联。他汀类药物的使用与复合结局事件（比值比0.84，95%置信区间0.58 - 1.23，P = 0.3）和缺血性结局事件（比值比1.17，95%置信区间0.73 - 1.88，P = 0.5）无关，而与出血性结局事件风险较低相关（比值比0.51，95%置信区间0.28 - 0.91，P = 0.02）。
他汀类药物因其全身抗炎和内皮保护作用，可保护脑动脉血管（尤其是小血管）免受高血压、糖尿病和其他有害因素（如活性氧、促炎细胞因子等）的亚急性损伤。
我们的数据表明，他汀类药物似乎可预防心源性栓塞性卒中患者的全身性出血事件；这可能归因于他汀类药物的多效性作用。需要更多数据来证实这些发现。
