Strokes prevention

Dipyridamole is a PDE5/PDE6 selective inhibitor that is used widely in conjunction with aspirin to reduce clotting and prevent stroke. More recent studies with a fixed combination of these two drugs (Aggrenox) has been shown in the recent European Stroke Prevention Study 2 to be of greatly added benefit over aspirin alone for prevention of recurrent stroke. 

Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO Task Force on Stroke and other Cerebrovascular Disorders. Stroke 1989 20 1407-1431. 

The European Stroke Prevention Study 2 (ESPS-2) trial examined four treatment arms—extended-release dipyridamole (ER-DP) 200 mg twice daily alone, aspirin 25 mg twice daily alone, ER-DP 200 mg twice daily + aspirin 25 mg twice daily, or placebo. In comparison with placebo the overall reduction in stroke risk was 16% with ER-DP alone and 18% with aspirin alone. The combination of ER-DP and aspirin led to a 37% reduction in stroke risk compared to placebo. Compared with aspirin alone, the combination of ER-DP with aspirin reduced the risk of stroke by 23%. 

The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) confirmed the finding of ESPS 2, showing that the combination of aspirin and dipyridamole is more effective than aspirin alone in the prevention of new vascular events in patients with nondisabling cerebral ischaemia of presumed arterial origin. Adding the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or MI of 0.82 (95% Cl 0.74-0.91). 

Diener HC, Cunha L, Forhes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and asetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 143 1-13. 

Hart RG, Halperin JL, Pearce LA, Anderson DC, Kronmal RA, McBride R, Nasco E, Sherman DG, Talbert RL, Marler JR. Lessons from the stroke prevention in atrial fibrillation trials. Ann Intern Med 2003 138 831-838. 

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. 

The majority of patients with AF should receive warfarin therapy (titrated to an International Normalized Ratio of 2 to 3) for stroke prevention, particularly if they have other risk factors for stroke. 

Stroke Prevention All patients with paroxysmal, persistent, or permanent AF should receive therapy for stroke prevention, unless compelling contraindications exist. A decision strategy for stroke prevention in AF is presented in Fig. 6-9.27 In general, most patients require therapy with warfarin in some patients with no additional risk factors for stroke, aspirin may be acceptable. For some patients, serious consideration of the benefits of warfarin versus the risks of bleeding associated with warfarin therapy is warranted. The potential bleeding risks associated with warfarin may outweigh the benefits in... 

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). 

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. 

Ticlopidine is slightly more beneficial in stroke prevention than aspirin in both men and women.31,32 The usual recommended dosage is 250 mg orally twice daily. Ticlopidine is costly, and side effects include bone marrow suppression, rash, diarrhea, and an increased cholesterol level. Neutropenia is seen in approximately 2% of patients. Thrombotic thrombocytopenic... 

Straus SE, Majumdar SR, McAlister FA. New evidence for stroke prevention scientific review. JAMA 2002 288 1388-1395. 

Primary indication stroke prevention in pediatric patients... 

Several methods of transfusion maybe used, including simple transfusion, exchange transfusion, or erythrocytapheresis. The goal of chronic transfusion therapy is to maintain the HbS level at less than 30% (0.30) of total hemoglobin concentration. Transfusions usually are administered every 3 to 4 weeks depending on the HbS concentration. For secondary stroke prevention, current studies have indicated that lifelong transfusion may be required, with an increased incidence of recurrence once transfusions are stopped.6... 

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. 

STOP Stroke Prevention Trial in Sickle Cell... 

The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Patients with nonvalvular atrial fibrillation at low risk of stroke dur-... 

Matchar DB, McCrory DC, Barnett HJM, Feussner JR. Medical treatment for stroke prevention. Ann Inter Med 1994 121 54-5. 

Diener HC. Stroke prevention Antiplatelet and an-tithrombolytic therapy. Haemostasis 2000 30 14-26. 

Verdecchia P et al Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention. Hypertension 2005 46 386. [PMID 16009786]... 

Stroke Prevention in Atrial Fibrillation Study Group of Investigators Special Report. N. Eng J. Med., 863 (March 22, 1990). 

Go AS, Fang MC, Singer DE. Antithrombotic therapy for stroke prevention in atrial fibrillation. Prog Cardiovasc Dis. 2005 48 108-124. 

Schmidt, R., Fazekas, F., Hayn, M., Schmidt, H., Kapeller, P., Toob, G., Offenbacher, H., Schumacher, M., Eber, B., Weinrauch, V., Kostner, G.M., and Esterbauer, H. 1997. Risk factors for microangiopathy-related cerebral damage in Aistrian stroke prevention study. J. Neurol. Sci. 152, 15-21. 

SPORTIF III Stroke prevention in nonvalvular atrial fibrillation Open-label 36 mg twice daily for at least 12 months Warfarin, target INR, 2.0-3.0 1704 1703 (60,83)... 

Olsson SB. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III) randomised controlled trial. Lancet 2003 362 1691-1698. 

Albers GW, Diener HC, Frison L, et al. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation a randomized trial. J Am Med Assoc 2005 293 690-698. 

Lip GY Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation A systematic review and meta-analysis. Thromb Res 2006 ... 

---