Ischemic stroke prevention

When the CAST collaborative group performed a meta-analysis of 1ST, CAST, and MAST-I, the trend seen in CAST and 1ST toward a beneficial effect of aspirin on the rate of death or dependency reached the threshold for statistical significance. Early aspirin therapy (160-300 mg/day) conferred an absolute reduction in the rate of recurrent ischemic stroke by 0.7% (7 per 1000 patients treated) (p < 0.001) and reduced the rate of death or dependency by 1.3% (13 per 1000 patients treated) (2p = 0.007). Aspirin caused about 2 hemorrhagic strokes among every 1000 patients treated, but prevented about 11 other strokes or deaths in hospital. 

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

Kamphuisen PW, Agnelli G. What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke Thromb Res 2007 119(3) 265-274. 

Five randomized primary and secondary prevention trials " have demonstrated the efficacy and safety of warfarin in preventing AF-related stroke. Pooled data from these trials demonstrated a 68% reduction in ischemic stroke (95% Cl 50-79) and an intracerebral hemorrhage rate of <1% per year. The data for aspirin suggested that it had a lesser effect, with a 36% risk reduction (95% Cl 4—57). 

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators High-dose atorvastatin after stroke or transients ischemic attack. N Engl J Med 2006 355 549-559. 

FIGURE 6-9. Decision algorithm for stroke prevention in atrial fibrillation.27 Risk factors for stroke prior transient ischemic attack or stroke hypertension heart failure rheumatic heart valve disease prosthetic heart valve. Target International Normalized Ratio = 2.5 (range 2 to 3). 

Develop an appropriate therapeutic plan for outpatient management of a patient with ischemic stroke, including an appropriate agent to prevent stroke recurrence. 

A major goal in the long-term treatment of ischemic stroke involves the prevention of a recurrent stroke through the reduction and modification of risk factors. 

Aspirin is typically considered to be the first-line secondary prevention agent for ischemic stroke and decreases the risk of subsequent stroke by approximately 25% in both men and women with previous transient ischemic attacks or stroke. 

Assessment of risk factors for ischemic stroke as well as for hemorrhagic stroke is an important component of the diagnosis and treatment of patients. A major goal in the long-term treatment of ischemic stroke involves the prevention of a recurrent stroke through the reduction and modification of risk factors. The major focus of primary prevention (prevention of the first stroke) is also reduction and modification of risk factors. Risk factors for ischemic stroke can be divided into modifiable and non-modifiable factors. Every patient should have risk factors assessed and treated, if possible, as management of risk factors can decrease the occurrence and/or recurrence of stroke.4... 

Randomized trials have been completed assessing the role of antiplatelet therapy with aspirin for primary stroke prevention. The use of aspirin in patients with no history of stroke or ischemic heart disease reduced the incidence of non-fatal myocardial infarction (MI) but not of stroke. A meta-analysis of eight trials found that the risk of stroke was slightly increased with aspirin use, especially hemorrhagic stroke. Major bleeding risk was also increased with aspirin use.4 Aspirin is beneficial in the primary prevention of MI, but not for primary stroke prevention. 

Chronic transfusion therapy is warranted to prevent serious complications from SCD, including stroke and recurrence. Especially in children, chronic transfusions have been shown to decrease stroke recurrence from approximately 50% to 10% over 3 years. Without chronic transfusions, approximately 70% of ischemic stroke patients will have another stroke. Chronic transfusion therapy also may be used to prevent vaso-occlusive pain and ACS, as well as prevent progression of... 

Early detection of ischemic stroke can be done with the use of transcranial Doppler ultrasonography. In the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study, screening with this method followed by transfusion significantly reduced the incidence of stroke.29 Screening is recommended in all patients over 2 years of age. 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

Stroke A stroke occurs when there is an interruption of blood supply to the brain. An ischemic stroke occurs when a clot prevents blood flow in the brain. A hemorrhagic stroke is when there is a rupture of a blood vessel in the brain. In either case, the brain cells in the affected area die. This area is called an infarct. Medical treatment is required to arrest the damage. More effective treatment can be administered within 6 hours of the onset of stroke. A stroke may result in weakness, paralysis, impairment of speech and memory, or even death. Medical treatment includes the use of anticoagulants to treat stroke victims. 

Tanne D et al. Blood lipids and first-ever ischemic stroke/transient ischemic attack in the Benzafibrate Infarction Prevention (BIP) Registry High triglycerides constitute an independent risk factor. Circulation 2001 104 2892-2897. 

The use of traditional (unffactionated) heparin has therefore been replaced by LMWHs to a large extent.18,100 LMWHs are clearly safer and more convenient to their unfractionated counterparts, and these drugs have become the primary method of treating acute venous thrombosis.47,100 LMWHs are now used routinely to prevent or treat deep vein thrombosis (DVT) following various types of surgery or medical conditions (ischemic stroke, cancer).70,127 It has also been suggested that LMWHs will produce optimal effects if they are administered for more than a few days, and some patients who are at high risk for thrombosis may receive LMWHs via subcutaneous injection for several weeks or months.80 Future research will help determine the best way to use LMWHs to prevent or treat venous thrombosis in specific clinical situations. 

Kamphuisen PW, Agnelli G, Sebastianelli M. Prevention of venous thromboembolism after acute ischemic stroke. J Thromb Haemost. 2005 3 1187-1194. 

Leonardi-Bee J, Bath PM, BousserMG, et al. Dipyridamole for preventing recurrent ischemic stroke and other vascular events a meta-analysis of individual patient data from randomized controlled trials. Stroke. 2005 36 162-168. 

Ling GS, Ling SM. Preventing ischemic stroke in the older adult. Cleve Clin J Med. 2005 72(suppl 3) S14-S25. 

IboleJF etal. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004 291 (5) 565-575. 

Goldstein LB, Adams R, Becker K, et al, Primary prevention of ischemic stroke a statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 2001 103 163-182,... 

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