engleski

Antiplatelet therapy in secondary prevention of stroke

Secondary prevention means treatment and rehabilitation of patients who have had a stroke, in order to prevent second stroke. Secondary prevention also means identification and treatment of persons at a very high risk of developing stroke, in order to prevent stroke occurrence. Secondary prevention can extend overall survival, improve quality of life, decrease the need of surgical procedures, and reduce the incidence of subsequent strokes. Secondary prevention includes the following: 1) changing lifestyle: quitting smoking, increasing physical activity, reducing body weight, changing eating habits ; 2) treatment of concomitant diseases: hypertension, diabetes, elevated plasma lipids, cardiac diseases, ar~d atrial fibrillation ; 3) surgical interventions, e.g., endarterectomy ; and 4) prescribing drugs for secondary prevention. The first three measures can be carried out in some patients, while the fourth measure can be carried out in all patients. In secondary prevention of stroke, antiplatelet drugs are prescribed, most often acetylsalicylic acid (ASA), ticlopidi, clopidogrel, and dipyridamole. The Antiplatelet Trialists' Collaboration have published an overview of all controlled clinical trials on the prevention of major vascular events available by March 1990. They concluded that odds reduction for the combined vascular outcome was 22%, and that relative risk reduction for stroke was 23%. ASA inhibits cyclo-oxygenase thereby suppressing the production of thromboxane A2 (TXA2) in platelets and prostacyclin (PGI) in endothelial cells. In the Antiplatelet Trialists Collaboration publication, ASA reduced the relative risk of vascular events by 20%-28%, depending on the dosage (the difference was not statistically significant). There still are some doubts about the optimal dosage of ASA, because in different studies doses of ASA ranged from 30 mg/day to 1300 mg/day. The UK-TIA Trial showed no difference between medium (300 mg/day) and high (1200 mg/day) dose of ASA, while Dutch TIA Trial found no difference between low (30 mg/day) and medium (283 mg/day) dose of ASA. It seems that ASA in any daily dose of 30 mg or higher reduces the risk of major vascular event by 20% at most. However, higher doses increase the incidence of side effects (gastrointestinal bleeding, indigestion heartburn, nausea, vomiting). In European countries, ASA is mainly prescribed in doses lower than 500 mg/day, while in the United States ASA is mainly prescribed in doses higher than 500 mg/day. Ticlopidine is a thienopyridine derivative that inhibits the adenosine diphosphate pathway of platelet aggregation. In the CATS, ticlopidine (500 mg/day) showed a 33% reduction of the risk of stroke. In the TASS, ticlopidine (500 mg/day) showed a 12% risk reduction compared with ASA (1300 mg/day) for stroke or death. Ticlopidine is therefore better or equal to ASA in the secondary prevention of stroke. However, a major disadvantage of ticlopidine are its side effects: diarrhea, skin rashes, neutropenia, thrombocytopenia, thrombocytopenic thrombotic purpura, and pancytopenia. Ticlopidine is a drug with more side effects than ASA, and it is much more expensive. Clopidogrel is chemically related to ticlopidine, and it inhibits the adenosine diphosphate pathway of platelet aggregation, In the CAPRIE study, clopidogrel (75 mg/day) showed a relative risk reduction of 8.7% compared with ASA (325 mg/day) for major vascular events. In contrast to ticlopidine, the overall safety profile of clopidogrel is at least as good as that of medium dose ASA. Concerning, different mechanisms of action a combination of ASA and clopidogrel is potentially attractive. It is assumed that dipyridamole inhibits platelet function in several ways: it inhibits phosphodiesterase resulting in an increase in intraplatelet antithrombotic cyclic adenosine monophosphate levels, it inhibits the cellular uptake and metabolism of adenosine, thereby increasing its plasma level, and it directly stimulates the release of prostacyclin by vascular endothelium. In the ESPS-1, a combination of ASA (990 mg/day) and dipyridamole (225 mg/day) reduced the risk of stroke by 38%. ESPS-2 showed a stroke relative risk reduction by 18% for ASA (50 mg/day), 16% for dipyridamole (400 mg/day), and 37% for the combination of ASA and dipyridamole. However, the AICLA and ACCSG trials did not show any significant difference between ASA alone and ASA in combination with dipyridamole. The unresolved question is for how long should antiplatelet agents be prescribed, however, most authors believe that the patient should be treated as long as the risk of stroke persists. Antiplatelet drugs approved in Croatia are ASA and ticlopidine, so in the secondary prevention of stroke these two drugs could be used.

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