Statin therapy and stroke prevention

Hypercholesterolemia has not traditionally been considered an important risk factor in the pathogenesis of stroke. However, recent studies show that statin therapy significantly reduces ischemic stroke for patients with established coronary artery disease. Statin therapy may reduce stroke through amelioration of precerebral atherosclerosis in the carotid artery and the aorta. Anti-atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur within the blood and in plaque. Statins may also protect against cerebral ischemia through beneficial modulation of the brain endothelial nitric oxide system. Ongoing studies are exploring the role of statin therapy in the primary prevention of stroke and in the prevention of cognitive decline and multi-infarct cerebrovascular disease.     

Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients

Purpose

More than 120,000 patients now have taken part in randomized trials evaluating statin therapy for stroke prevention. We aimed to conduct a comprehensive review of all randomized trials and determine the therapeutic potential of statins for all strokes.

Methods

We searched 10 electronic databases (from inception to December 2006). We additionally contacted study authors and authors of previous reviews. We extracted data on study characteristics and outcomes related to all-cause mortality, all-stroke incidence, specific type of strokes, and cholesterol changes. We pooled data using a random-effects model and conducted meta-regression.

Results

We included 42 trials assessing statin therapy for all-stroke prevention (n = 121,285), resulting in a pooled relative risk (RR) of 0.84 (95% confidence interval [CI], 0.79-0.91). The pooled RR of statin therapy for all-cause mortality (n = 116,080) was 0.88 (95% CI, 0.83-0.93). Each unit increase in low-density lipoprotein (LDL) resulted in a 0.3% increased RR of death (P = .02). Seventeen trials evaluated statins on cardiovascular death (n = 57,599, RR 0.81, 95% CI, 0.74-0.90), and 11 evaluated nonhemorrhagic cerebrovascular events (n = 58,604, RR 0.81, 95% CI, 0.69-0.94). Eleven trials reported hemorrhagic stroke incidence (total n = 54,334, RR 0.94, 95% CI, 0.68-1.30) and 21 trials reported on fatal strokes (total n = 82,278, RR 0.99, 95% CI, 0.80-1.21). Only one trial reported on statin therapy for secondary prevention.

Conclusions

Statin therapy provides high levels of protection for all-cause mortality and nonhemorrhagic strokes. This overview reinforces the need to consider prolonged statin treatment in patients at high risk of major vascular events, but caution remains for patients at risk of bleeds.     

Statin therapy for coronary heart disease and its effect on stroke

Coronary heart disease (CHD) and stroke share common risk factors and are the leading causes of death and disability in the United States. Although the impact of elevated cholesterol on stroke risk has been disputed, numerous trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (ie, statins) in patients with CHD have demonstrated a significant reduction in stroke incidence as a secondary endpoint. It is likely that statins are pleiotropic in stroke prevention, providing benefits through both cholesterol reduction and cholesterol-independent mechanisms. In this article, we review the relationship between cholesterol and stroke, randomized trials of statins in patients with CHD and high risk for CHD that have assessed stroke risk, and the putative mechanisms of stroke prevention by statins.     

Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.

PURPOSE: To characterize the efficacy and safety of anticoagulants and antiplatelet agents for prevention of stroke in patients with atrial fibrillation. DATA SOURCES: Randomized trials identified by using the search strategy developed by the Cochrane Collaboration Stroke Review Group. STUDY SELECTION: All published randomized trials testing antithrombotic agents to prevent stroke in patients with atrial fibrillation. DATA EXTRACTION: Data on interventions, number of participants, duration of exposure and occurrence of all stroke (ischemic and hemorrhagic), major extracranial bleeding, and death were extracted independently by two investigators. DATA SYNTHESIS: Sixteen trials included a total of 9874 participants (mean follow-up, 1.7 years). Adjusted-dose warfarin (six trials, 2900 participants) reduced stroke by 62% (95% CI, 48% to 72%); absolute risk reductions were 2.7% per year for primary prevention and 8.4% per year for secondary prevention. Major extracranial bleeding was increased by warfarin therapy (absolute risk increase, 0.3% per year). Aspirin (six trials, 3119 participants) reduced stroke by 22% (CI, 2% to 38%); absolute risk reductions were 1.5% per year for primary prevention and 2.5% per year for secondary prevention. Adjusted-dose warfarin (five trials, 2837 participants) was more efficacious than aspirin (relative risk reduction, 36% [CI, 14% to 52%]). Other randomized comparisons yielded inconclusive results. CONCLUSIONS: Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more efficacious than aspirin. The benefit of antithrombotic therapy was not offset by the occurrence of major hemorrhage among participants in randomized trials. Judicious use of antithrombotic therapy, tailored according to the inherent risk for stroke, importantly reduces stroke in patients with atrial fibrillation.     

Drug insight: Statin use in the elderly

The elderly represent a notable proportion of patients who present with myocardial infarction or acute coronary syndromes. This subgroup of patients also experiences a higher incidence of adverse outcomes than younger age-groups, and, therefore, has more to gain from effective, evidence-based therapies. The efficacy of statins in secondary cardiovascular disease prevention is firmly established. The starting of therapy soon after an acute coronary event has been shown to provide added benefit. Uncertainties about the effectiveness of statins in the elderly, however, have resulted in their underuse in this population. In this review we evaluate the evidence for statin use in this important and increasingly large group of patients.     

How to prevent perioperative delirium in the elderly?

Due to increasing life expectancy, the number of elderly patients needing surgical care is increasing. Improvements in surgical techniques and anesthetic procedures offer the opportunity of surgical intervention even in frail patients. Delirium on admission to the hospital or in the perioperative setting is a common and often serious complication. Cognitive impairment is regarded as the main risk factor for delirium; unfortunately, under routine clinical conditions, these deficits often remain undetected. Postoperative delirium is associated with increased morbidity and mortality, as well as increased length of hospitalization, resulting in increased suffering and costs. The aim of the intervention presented here was to prevent delirium in a general hospital without a geriatric specialty department. Geriatric nurses became part of the team in the perioperative setting, giving psychological support and being a continuous companion to the patient and his/her proxies. Co-operation between all professions involved throughout hospitalization of the patient was emphasized. The low incidence of delirium in elderly surgical patients resulting from our efforts indicate that – for this setting in a general hospital – the strategy was effective for the prevention of delirium. Nowadays, geriatric nurses are an essential part of the perioperative team and delirium has lost much of its imminence.     

How to prevent perioperative delirium in the elderly?

Due to increasing life expectancy, the number of elderly patients needing surgical care is increasing. Improvements in surgical techniques and anesthetic procedures offer the opportunity of surgical intervention even in frail patients. Delirium on admission to the hospital or in the perioperative setting is a common and often serious complication. Cognitive impairment is regarded as the main risk factor for delirium; unfortunately, under routine clinical conditions, these deficits often remain undetected. Postoperative delirium is associated with increased morbidity and mortality, as well as increased length of hospitalization, resulting in increased suffering and costs. The aim of the intervention presented here was to prevent delirium in a general hospital without a geriatric specialty department. Geriatric nurses became part of the team in the perioperative setting, giving psychological support and being a continuous companion to the patient and his/her proxies. Co-operation between all professions involved throughout hospitalization of the patient was emphasized. The low incidence of delirium in elderly surgical patients resulting from our efforts indicate that – for this setting in a general hospital – the strategy was effective for the prevention of delirium. Nowadays, geriatric nurses are an essential part of the perioperative team and delirium has lost much of its imminence.     

他汀类药物与卒中防治

近2／3的缺血性卒中患者有动脉粥样硬化，其卒中由大动脉粥样硬化或小动脉血管病变引起。脑缺血由动脉狭窄或闭塞造成，或来自复合动脉粥样硬化斑块的栓子脱落导致血流减少引起。动脉粥样硬化是狭窄的最主要原因，其过程复杂，涉及血管内皮损伤、炎症、脂质沉积、血管平滑肌增生、粥样硬化斑块形成、纤维化、血小板和凝血酶激活。鉴于他汀类药物（以下简称他汀类）降脂治疗与卒中防治的研究渐成热点，现将他汀类在卒中预防和治疗中的作用，以及重要的临床试验证据综述如下。