Although worldwide stroke epidemiology has changed, the burden of stroke remains high. According to the Global Burden of Disease Study, despite a 28% increase in the absolute number of cerebrovascular deaths, there was a 36% decline in the age-standardized mortality rate in most regions of the world in the period from 1990 to 2016. In 2016, 5.5 million deaths worldwide were attributed to stroke, which continues to be the second leading cause of mortality. Additionally, there were 80 million stroke survivors globally in 2016 and a 2.6% increase in the ischemic stroke rate from 2006 to 2016. Stroke also remains the leading cause of long-term disability worldwide, despite a 34% decrease in the global age-standardized YLD (years lived with disability) rate (55).
There are approximately 800,000 strokes per year in the United States, 23% of which are recurrent. Moreover, nearly one sixth of ischemic strokes are preceded by a transient ischemic attack. Most recurrent strokes are of the same subtype as the index event, and 1-year stroke recurrence rates are higher for infarcts due to large artery disease than for other ischemic stroke subtypes (140). Prevention of stroke and transient ischemic attack includes both conventional approaches to vascular risk factor management (blood pressure lowering, cholesterol reduction with statins, smoking cessation, and antiplatelet therapy) and more specific interventions, such as carotid revascularization or anticoagulation for atrial fibrillation. In this article, the authors discuss effective interventions for optimal secondary stroke prevention.
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• Each year, 1 of every 5 strokes is recurrent, and most are the same subtype as the index event.
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• Identifying and appropriately managing major modifiable stroke risk factors is essential, along with behavioral and lifestyle modifications, for preventing recurrence in individuals with either a first transient ischemic attack or a first stroke.
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• Multidisciplinary management of modifiable risk factors is advisable and should be based on therapies optimally tailored in accordance with the patient’s comorbidities and the etiology of the preceding stroke or transient ischemic attack.
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• Long-term antiplatelet therapy or anticoagulation, depending on index stroke etiology, is recommended in nearly all patients to reduce stroke recurrence risk.
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• Carotid revascularization and percutaneous patent foramen ovale closure are recommended in carefully selected patients.
History of antithrombotic therapy for prevention of stroke.
Antiplatelet agents. Because it was known to cause bleeding, aspirin was first suggested as an antithrombotic drug in 1953 by Lawrence Craven, a general practitioner working in Glendale, a suburb of Los Angeles, California (42). The antiplatelet effects were not discovered until the late 1960s (143) after which several trials were started (52; 09). The benefit of aspirin was demonstrated in reducing the incidence of stroke in patients with prior symptomatic cerebrovascular disease; from this, aspirin has become the mainstay of secondary stroke prevention. Aspirin is also beneficial for acute stroke patients (15; 16). Demonstrations of further benefit by other antiplatelet agents were evidenced by well-designed clinical trials. Ticlopidine, clopidogrel, and a combination of dipyridamole plus aspirin are available for patients requiring a drug other than aspirin (71; 14; 49).
Anticoagulants. What came to be called heparin was discovered in 1916 (101) and used in patients from the 1930s whereas oral anticoagulants were discovered in the 1930s and introduced into clinical practice in the 1940s (96). After the clinical and autopsy studies linking nonvalvular atrial fibrillation to stroke, data from epidemiological studies demonstrated this condition to be the most powerful precursor of stroke, particularly in the elderly (145). The 5-fold increased incidence of stroke in patients with atrial fibrillation was significantly reduced in a remarkable series of randomized clinical trials on warfarin anticoagulation conducted in the late 1980s and early 1990s in primary and secondary prevention of stroke (13). Anticoagulation with warfarin to achieve a well-defined level of anticoagulation (INR between 2 and 3) has been shown to be effective and generally safe in patients with atrial fibrillation. But for patients with sinus rhythm, the enthusiasts were wrong, and so far there has been no trial evidence indicating that warfarin is better than aspirin (106).
Carotid endarterectomy is 1 of the most common vascular and neurosurgical operations. However, controversies regarding its indication and safety required several decades before general resolution, and its methodology is still being debated. After early failures in China (33) and Argentina (30), the first successful carotid endarterectomy was performed in the United States in 1953 by DeBakey in 1975 (43). However, even 30 years after the first surgical treatment of carotid stenosis, physicians were questioning the utility of the procedure in light of the high rate of perioperative complications. In 1962, WS Fields started the first randomized trial of carotid endarterectomy (53). This trial demonstrated the benefit of the procedure in stroke prevention, but a high rate of complications tarnished the results. In 1987, HJM Barnett designed a large-scale clinical trial to evaluate risks and benefits of carotid endarterectomy in symptomatic patients with transient ischemic ataxia or minor stroke: the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Results of this study reported in 1991 clearly demonstrated the benefit of the surgical procedure in patients with stenosis of the internal carotid artery greater than 70% (11). Also, a European trial, the European Carotid Study Trial, showed the same benefit from surgery in comparison to medical treatment for patients with symptomatic severe carotid stenosis (10). Since these results were published, the number of carotid endarterectomies performed for stroke prevention has gradually increased.