Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke.
Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.
Weinberger
Jesse
J
Neurovascular Laboratory, Department of Neurology, The Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1052, New York, NY 10029, USA. jesse.weinberger@mssm.edu
D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects; D000077144:Clopidogrel; D004176:Dipyridamole / Q000009:adverse effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012459:Salicylates / Q000009:adverse effects; D020521:Stroke / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D014859:Warfarin / Q000009:adverse effects
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; D014859:Warfarin; D004176:Dipyridamole; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
Rev Neurol Dis. 2004 Spring;1(2):91-4
16400264
JAMA. 1998 Apr 22-29;279(16):1278-81
9565008
Lancet. 1996 Nov 16;348(9038):1329-39
8918275
Am J Med. 2003 Jan;114(1):77-8
12543298
Neurology. 2004 Sep 28;63(6):1099-101
15452309
Am Heart J. 2000 Jul;140(1):67-73
10874265
Circulation. 2003 Jan 7;107(1):32-7
12515739
Stroke. 2004 Feb;35(2):533-7
14707231
Stroke. 1999 Sep;30(9):1991-4
10471455
Lancet. 2004 May 8;363(9420):1491-502
15135594
Stroke. 1980 Sep-Oct;11(5):433-42
6999670
N Engl J Med. 2000 Jun 15;342(24):1773-7
10852999
Stroke. 2003 Apr;34(4):840-8
12649515
Lancet. 1978 Jun 17;1(8077):1286-9
78050
Ann Neurol. 1997 Dec;42(6):857-65
9403477
Stroke. 1990 Dec;21(12 Suppl):IV12-23
2124385
Circulation. 2003 Apr 1;107(12):1568-9
12668486
N Engl J Med. 1991 Oct 31;325(18):1261-6
1922220
N Engl J Med. 1978 Jul 13;299(2):53-9
351394
N Engl J Med. 2001 Aug 16;345(7):494-502
11519503
Am J Health Syst Pharm. 2002 Sep 15;59(18):1723-35
12298110
Arterioscler Thromb. 1993 Aug;13(8):1171-9
8343491
N Engl J Med. 1991 Aug 15;325(7):445-53
1852179
Lancet. 1989 Jun 3;1(8649):1215-20
2566778
Thromb Haemost. 1990 Aug 13;64(1):150-5
2274920
Stroke. 1996 Sep;27(9):1459-66
8784113
Lancet. 2004 Jul 24-30;364(9431):331-7
15276392
BMJ. 1994 Jan 8;308(6921):81-106
8298418
Expert Rev Cardiovasc Ther. 2004 Mar;2(2):163-74
15151465
Neurology. 1995 Aug;45(8):1488-93
7644046
Circulation. 2003 Oct 7;108(14):1682-7
14504182
JAMA. 1999 Mar 3;281(9):806-10
10071001
Stroke. 2004 Feb;35(2):537-8
14757895
Circulation. 2001 Jan 23;103(3):363-8
11157686
Neurology. 1998 Jan;50(1):208-16
9443482
Stroke. 1982 May-Jun;13(3):290-5
7080120
Stroke. 1985 May-Jun;16(3):406-15
2860740
J Neurol Sci. 1996 Nov;143(1-2):1-13
8981292
JAMA. 1995 May 10;273(18):1421-8
7723155
Arch Neurol. 1992 Aug;49(8):857-63
1524519
Ann Intern Med. 1998 Apr 1;128(7):541-4
9518398
J Clin Invest. 1975 Sep;56(3):624-32
1159076
N Engl J Med. 2001 Nov 15;345(20):1444-51
11794192
Eur J Pharmacol. 2004 Sep 24;499(3):315-24
15381054
Stroke. 2002 Oct;33(10):2499-505
12364744
Neurology. 1992 Jan;42(1):111-5
1734290
Lancet. 2003 Nov 22;362(9397):1691-8
14643116
JAMA. 2003 Nov 26;290(20):2685-92
14645310
Stroke. 2002 Apr;33(4):901-6
11935034
Stroke. 1990 Aug;21(8):1122-30
2202093
Stroke. 1998 Feb;29(2):415-21
9472883
J Neurol Neurosurg Psychiatry. 1991 Dec;54(12 ):1044-54
1783914
Lancet. 1998 Sep 26;352(9133):1036-7
9759754
Stroke. 2001 Oct;32(10):2394-402
11588332
JAMA. 2003 Jun 11;289(22):2947-57
12799402
Stroke. 2001 Dec 1;32(12):2948-9
11740003
Arch Intern Med. 1999 Nov 22;159(21):2524-8
10573042
N Engl J Med. 1989 Aug 24;321(8):501-7
2761587
Lancet. 1994 Mar 19;343(8899):687-91
7907677