Skip to main content
Top
Published in: Drug Safety 13/2002

01-11-2002 | Review Article

A Benefit-Risk Assessment of Agents Used in the Secondary Prevention of Stroke

Authors: Dr Ronald S. MacWalter, Colin P. Shirley

Published in: Drug Safety | Issue 13/2002

Login to get access

Abstract

Stroke is a major cause of morbidity and mortality. Full assessment of stroke or transient ischaemic attack (TIA) patients is required to identify all risk factors and apply appropriate secondary preventative strategies.
Antiplatelet therapies are effective in the secondary prevention of ischaemic stroke and can be justified despite adverse effects such as gastrointestinal haemorrhage. Aspirin (acetylsalicylic acid), aspirin plus dipyridamole, ticlopidine and clopidogrel are all of value but their adverse effect profiles vary significantly. Combinations of antiplatelet agents may offer additional benefit but not all combinations have been studied in stroke patients. Anticoagulation with agents such as warfarin is effective with coexisting atrial fibrillation and other conditions predisposing to cardioembolic stroke. Antihypertensive agents have been extensively studied in the primary prevention of stroke; however, relatively few trials of antihypertensive agents in the secondary prevention of stroke are available. The incidence of adverse effects of antihypertensive agents is relatively low and the benefit-risk profile would tend to favour their use in the secondary prevention of stroke. Recent studies of ACE inhibitors have identified an important role for these agents in the secondary prevention of stroke even in those who are normotensive and in those who have had a haemorrhagic stroke. The incidence of serious adverse effects with ACE inhibitors appears relatively low.
Lipid-lowering agents may have a role to play in certain groups of patients with stroke. The incidence of adverse effects is relatively low with HMG-CoA reductase inhibitors.
Cigarette smoking is an important risk factor for stroke and evidence is available that smoking cessation does reduce the individualbs risk of stroke. Pharmacological agents are available to help smoking cessation.
In patients with diabetes mellitus, intensive regimens with insulin and oral hypoglycaemic agents have so far not definitively been shown to reduce the incidence of macrovascular complications such as stroke. Tight glycaemic control has been shown to improve microvascular complications such as retinopathy, nephropathy and neuropathy and hence this is reason enough to advocate the use of these agents. Future developments in the treatment of diabetes may help.
Secondary prevention of stroke has improved greatly over the past decade and hopefully will continue to improve. The use of pharmacological agents available currently and in the future will be clarified and refined as further clinical trials report.
Literature
1.
go back to reference Grieve R, Hutton J, Bhalla A, et al. A comparison of the costs and survival of hospital-admitted stroke patients across Europe. Stroke 2001 Jul 1 32: 1684–91PubMedCrossRef Grieve R, Hutton J, Bhalla A, et al. A comparison of the costs and survival of hospital-admitted stroke patients across Europe. Stroke 2001 Jul 1 32: 1684–91PubMedCrossRef
2.
go back to reference Caro JJ, Huybrechts KF. Stroke treatment economic model (STEM): predicting long-term costs from functional status. Stroke 1999; 30: 2574–9PubMedCrossRef Caro JJ, Huybrechts KF. Stroke treatment economic model (STEM): predicting long-term costs from functional status. Stroke 1999; 30: 2574–9PubMedCrossRef
3.
go back to reference Terent A. Stroke morbidity in stroke: populations, cohorts, and clinical trials. Oxford: Butterworth-Heineman, 1993 Terent A. Stroke morbidity in stroke: populations, cohorts, and clinical trials. Oxford: Butterworth-Heineman, 1993
4.
go back to reference Dyken ML, Pokras R. The performance of endarterectomy for disease of the extracranial arteries of the head. Stroke 1984; 15: 948–50PubMedCrossRef Dyken ML, Pokras R. The performance of endarterectomy for disease of the extracranial arteries of the head. Stroke 1984; 15: 948–50PubMedCrossRef
5.
go back to reference Wolf PA, D’Agostino RB, O’Neal MA, et al. Secular trends in stroke incidence and mortality. The Framingham Study. Stroke 1992 23: 1551–5CrossRef Wolf PA, D’Agostino RB, O’Neal MA, et al. Secular trends in stroke incidence and mortality. The Framingham Study. Stroke 1992 23: 1551–5CrossRef
6.
go back to reference Department of Health. Health of the Nation: a strategy for health in England. London: HMSO, 1992 Department of Health. Health of the Nation: a strategy for health in England. London: HMSO, 1992
7.
go back to reference Wade DT. Stroke: acute cerebrovascular disease. In: Stevens A, Raftery J, editors. Health care needs assessment: the epidemiologically based needs assessment reviews. Vol. 1. Oxford: Radcliffe Medical Press, 1994 Wade DT. Stroke: acute cerebrovascular disease. In: Stevens A, Raftery J, editors. Health care needs assessment: the epidemiologically based needs assessment reviews. Vol. 1. Oxford: Radcliffe Medical Press, 1994
9.
go back to reference Ramasubbu R. Relationship between depression and cerebrovascular disease: conceptual issues. J Affect Disord 2000; 57: 1–11PubMedCrossRef Ramasubbu R. Relationship between depression and cerebrovascular disease: conceptual issues. J Affect Disord 2000; 57: 1–11PubMedCrossRef
10.
go back to reference Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994 Aug 1; 308: 81–106 Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 1994 Aug 1; 308: 81–106
11.
go back to reference Warner TD. Relationships between the endothelin and nitric oxide pathways. Clin Exp Pharmacol Physiol 1999; 26: 247–52PubMedCrossRef Warner TD. Relationships between the endothelin and nitric oxide pathways. Clin Exp Pharmacol Physiol 1999; 26: 247–52PubMedCrossRef
12.
go back to reference The International Stroke Trial (IST). A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997 May 31; 349: 1569–81 The International Stroke Trial (IST). A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997 May 31; 349: 1569–81
13.
go back to reference Chinese Acute Stroke Trial (CAST). A randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997 Jun 7; 349: 1641–9 Chinese Acute Stroke Trial (CAST). A randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997 Jun 7; 349: 1641–9
14.
go back to reference Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12; 324: 71–86 Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12; 324: 71–86
15.
go back to reference Swedish Aspirin Low-Dose Trial (SALT) of 75mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. The SALT Collaborative Group. Lancet 1991 Nov 30; 338: 1345–9 Swedish Aspirin Low-Dose Trial (SALT) of 75mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. The SALT Collaborative Group. Lancet 1991 Nov 30; 338: 1345–9
16.
go back to reference The Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30mg vs 283mg a day) in patients after a transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group. N Engl J Med 1991 Oct 31; 325: 1261–6 The Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30mg vs 283mg a day) in patients after a transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group. N Engl J Med 1991 Oct 31; 325: 1261–6
17.
go back to reference Farrell B, Godwin J, Richards S, et al. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991 54: 1044–54PubMedCrossRef Farrell B, Godwin J, Richards S, et al. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991 54: 1044–54PubMedCrossRef
18.
go back to reference Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000 Nov 11; 321: 1183–7PubMedCrossRef Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000 Nov 11; 321: 1183–7PubMedCrossRef
19.
go back to reference Gustafsson D, Nystrom J, Carlsson S, et al. The direct thrombin inhibitor melagatran and its oral prodrug h 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb Res 2001 Feb 1 101: 171–81PubMedCrossRef Gustafsson D, Nystrom J, Carlsson S, et al. The direct thrombin inhibitor melagatran and its oral prodrug h 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb Res 2001 Feb 1 101: 171–81PubMedCrossRef
20.
go back to reference Hawkey CJ. Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs. Gut 2000; 46: 310–1hPubMedCrossRef Hawkey CJ. Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs. Gut 2000; 46: 310–1hPubMedCrossRef
21.
go back to reference Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002 16: 779–86PubMedCrossRef Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002 16: 779–86PubMedCrossRef
22.
go back to reference Barnett HJ, Eliasziw M, Meldrum HE. Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995 Jan 26; 332: 238–48PubMedCrossRef Barnett HJ, Eliasziw M, Meldrum HE. Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995 Jan 26; 332: 238–48PubMedCrossRef
23.
go back to reference Algra A, van Gijn J. Aspirin at any dose above 30mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 1996; 60: 197–9PubMedCrossRef Algra A, van Gijn J. Aspirin at any dose above 30mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 1996; 60: 197–9PubMedCrossRef
24.
go back to reference Barnett HJ, Kaste M, Meldrum H, et al. Aspirin dose in stroke prevention: beautiful hypotheses slain by ugly facts. Stroke 1996; 27: 588–92PubMedCrossRef Barnett HJ, Kaste M, Meldrum H, et al. Aspirin dose in stroke prevention: beautiful hypotheses slain by ugly facts. Stroke 1996; 27: 588–92PubMedCrossRef
25.
go back to reference Komiya T, Kudo M, Urabe T, et al. Compliance with antiplatelet therapy in patients with ischemic cerebrovascular disease: assessment by platelet aggregation testing. Stroke 1994; 25: 2337–42PubMedCrossRef Komiya T, Kudo M, Urabe T, et al. Compliance with antiplatelet therapy in patients with ischemic cerebrovascular disease: assessment by platelet aggregation testing. Stroke 1994; 25: 2337–42PubMedCrossRef
26.
go back to reference Helgason CM, Bolin KM, Hoff JA, et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994 25: 2331–6PubMedCrossRef Helgason CM, Bolin KM, Hoff JA, et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994 25: 2331–6PubMedCrossRef
27.
go back to reference McGeehan M, Bush RK. The mechanisms of aspirin-intolerant asthma and its management. Curr Allergy Asthma Rep 2002; 2: 117–25PubMedCrossRef McGeehan M, Bush RK. The mechanisms of aspirin-intolerant asthma and its management. Curr Allergy Asthma Rep 2002; 2: 117–25PubMedCrossRef
28.
go back to reference Chen ZM, Sandercock P, Pan HC. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40 000 randomized patients from a Chinese acute stroke trial and the International Stroke Trial. J Intern Med Suppl 2000; 31: 1240–9 Chen ZM, Sandercock P, Pan HC. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40 000 randomized patients from a Chinese acute stroke trial and the International Stroke Trial. J Intern Med Suppl 2000; 31: 1240–9
29.
go back to reference Boysen G. Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit-risk analysis. J Intern Med 1999; 246: 239–45PubMedCrossRef Boysen G. Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit-risk analysis. J Intern Med 1999; 246: 239–45PubMedCrossRef
30.
go back to reference Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001 Dec 12 345: 1809–17PubMedCrossRef Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001 Dec 12 345: 1809–17PubMedCrossRef
31.
go back to reference Eikelboom JW, Hirsh J, Weitz JI, et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650–5PubMedCrossRef Eikelboom JW, Hirsh J, Weitz JI, et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650–5PubMedCrossRef
32.
go back to reference Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 1998; 114: 470S–88SPubMedCrossRef Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 1998; 114: 470S–88SPubMedCrossRef
33.
go back to reference Bousser MG, Eschwege E, Haguenau M, et al. ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 1983; 14: 5–14PubMedCrossRef Bousser MG, Eschwege E, Haguenau M, et al. ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 1983; 14: 5–14PubMedCrossRef
34.
go back to reference Guiraud-Chaumeil B, Rascol A, David J, et al. Prevention of recurrences of cerebral ischemic vascular accidents by platelet antiaggregants: results of a 3-year controlled therapeutic trial. Rev Neurol (Paris) 1982 138: 367–85 Guiraud-Chaumeil B, Rascol A, David J, et al. Prevention of recurrences of cerebral ischemic vascular accidents by platelet antiaggregants: results of a 3-year controlled therapeutic trial. Rev Neurol (Paris) 1982 138: 367–85
35.
go back to reference Diener HC, Cunha L, Forbes C, et al. European stroke prevention study: 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 143: 1–13PubMedCrossRef Diener HC, Cunha L, Forbes C, et al. European stroke prevention study: 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 143: 1–13PubMedCrossRef
36.
go back to reference Muller TH, Su CA, Weisenberger H, et al. Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo. Br J Clin Pharmacol 1990 30: 179–86PubMedCrossRef Muller TH, Su CA, Weisenberger H, et al. Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo. Br J Clin Pharmacol 1990 30: 179–86PubMedCrossRef
37.
go back to reference Virtanen KS, Mattila S, Jarvinen A, et al. Angiographic findings in patients exhibiting ischemia after oral dipyridamole. Int J Cardiol 1989 23: 33–6PubMedCrossRef Virtanen KS, Mattila S, Jarvinen A, et al. Angiographic findings in patients exhibiting ischemia after oral dipyridamole. Int J Cardiol 1989 23: 33–6PubMedCrossRef
38.
go back to reference Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989 Jun 3 I: 1215–20CrossRef Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989 Jun 3 I: 1215–20CrossRef
39.
go back to reference Hass WK, Easton JD, Adams Jr HP, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989 Aug 24; 321: 501–7PubMedCrossRef Hass WK, Easton JD, Adams Jr HP, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989 Aug 24; 321: 501–7PubMedCrossRef
40.
go back to reference Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996 Nov 16; 348: 1329–39 Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996 Nov 16; 348: 1329–39
41.
go back to reference Harker LA, Boissel J-P, Pilgrim AJ, the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) Steering Committee and Investigators, et al. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE trial. Drug Saf 1999; 21(4): 325–35PubMedCrossRef Harker LA, Boissel J-P, Pilgrim AJ, the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) Steering Committee and Investigators, et al. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE trial. Drug Saf 1999; 21(4): 325–35PubMedCrossRef
42.
go back to reference Trontell AE, Honig PK. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–2PubMedCrossRef Trontell AE, Honig PK. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–2PubMedCrossRef
43.
go back to reference Salliere D, Kassler-Taub KB. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–4PubMedCrossRef Salliere D, Kassler-Taub KB. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–4PubMedCrossRef
44.
go back to reference Mohr JP, Thompson JLP, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001 Nov 15 345: 1444–51PubMedCrossRef Mohr JP, Thompson JLP, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001 Nov 15 345: 1444–51PubMedCrossRef
45.
go back to reference De Schryver EL. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Cerebrovasc Dis 2000; 10: 147–50PubMedCrossRef De Schryver EL. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Cerebrovasc Dis 2000; 10: 147–50PubMedCrossRef
46.
go back to reference Diener HC, Ringleb P. Antithrombotic secondary prevention after stroke. 2001; 3: 451–62 Diener HC, Ringleb P. Antithrombotic secondary prevention after stroke. 2001; 3: 451–62
47.
go back to reference Rho R, DeNofrio D, Loh E. Cardiomyopathy and embolization: risks and benefits of anticoagulation in sinus rhythm. Curr Cardiol Rep 2000; 2: 106–11PubMedCrossRef Rho R, DeNofrio D, Loh E. Cardiomyopathy and embolization: risks and benefits of anticoagulation in sinus rhythm. Curr Cardiol Rep 2000; 2: 106–11PubMedCrossRef
48.
go back to reference Stein PD, Alpert JS, Bussey HI, et al. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001 119: 220S–7SPubMedCrossRef Stein PD, Alpert JS, Bussey HI, et al. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001 119: 220S–7SPubMedCrossRef
49.
go back to reference Lowe GD, Jaap AJ, Forbes CD. Relation of atrial fibrillation and high haematocrit tomortality in acute stroke. Lancet 1983 Apr 9; I: 784–6CrossRef Lowe GD, Jaap AJ, Forbes CD. Relation of atrial fibrillation and high haematocrit tomortality in acute stroke. Lancet 1983 Apr 9; I: 784–6CrossRef
50.
go back to reference Sandercock P, Bamford J, Dennis M, et al. Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). BMJ 1992f Dec 12; 305: 1460–5PubMedCrossRef Sandercock P, Bamford J, Dennis M, et al. Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). BMJ 1992f Dec 12; 305: 1460–5PubMedCrossRef
51.
go back to reference Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994 Jul 11; 154: 1449–57 Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994 Jul 11; 154: 1449–57
52.
go back to reference Stroke Prevention in Atrial Fibrillation III. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996 Sep 7; 348: 633–8 Stroke Prevention in Atrial Fibrillation III. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996 Sep 7; 348: 633–8
53.
go back to reference Hart RG, Benavente O, McBride R, et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999 Oct 5 131: 492–501PubMed Hart RG, Benavente O, McBride R, et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999 Oct 5 131: 492–501PubMed
54.
go back to reference European Atrial Fibrillation Trial (EAFT) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT Study Group. Lancet 1993 Nov 20; 342: 1255–62 European Atrial Fibrillation Trial (EAFT) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT Study Group. Lancet 1993 Nov 20; 342: 1255–62
55.
go back to reference Atrial Fibrillation Investigators. The efficacy of aspirin in patients with atrial fibrillation: analysis of pooled data from three randomized trials. The Atrial Fibrillation Investigators. Arch Intern Med 1997 Jun 9; 157: 1237–40 Atrial Fibrillation Investigators. The efficacy of aspirin in patients with atrial fibrillation: analysis of pooled data from three randomized trials. The Atrial Fibrillation Investigators. Arch Intern Med 1997 Jun 9; 157: 1237–40
56.
go back to reference Consensus Conference on Atrial Fibrillation. Consensus conference on atrial fibrillation in hospital and general practice. Scott Med J 1998; 43: 166–7 Consensus Conference on Atrial Fibrillation. Consensus conference on atrial fibrillation in hospital and general practice. Scott Med J 1998; 43: 166–7
57.
go back to reference Laupacis A, Albers G, Dalen J, et al. Antithrombotic therapy in atrial fibrillation. Chest 1995 108: 352S–9SPubMedCrossRef Laupacis A, Albers G, Dalen J, et al. Antithrombotic therapy in atrial fibrillation. Chest 1995 108: 352S–9SPubMedCrossRef
58.
go back to reference Halperin JL, Petersen P. Thrombosis in the cardiac chambers: ventricular dysfunction and atrial fibrillation. In: Verstrate M, Fuster V, Topol EJ, editors. Cardiovascular thromboepidemiology and thromboneurology. Philadelphia (PA): Lippincott-Raven, 1998 Halperin JL, Petersen P. Thrombosis in the cardiac chambers: ventricular dysfunction and atrial fibrillation. In: Verstrate M, Fuster V, Topol EJ, editors. Cardiovascular thromboepidemiology and thromboneurology. Philadelphia (PA): Lippincott-Raven, 1998
59.
go back to reference Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8PubMedCrossRef Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8PubMedCrossRef
60.
go back to reference Levine HJ, Pauker SG, Eckman MH. Antithrombotic therapy in valvular heart disease. Chest 1995; 108: 360S–70SPubMedCrossRef Levine HJ, Pauker SG, Eckman MH. Antithrombotic therapy in valvular heart disease. Chest 1995; 108: 360S–70SPubMedCrossRef
61.
go back to reference Gohlke-Barwolf C, Acar J, Burckhardt D, et al. Guidelines for prevention of thromboembolic events in valvular heart disease. Ad Hoc Committee of the Working Group on Valvular Heart Disease, European Society of Cardiology. J Heart Valve Dis 1993; 2: 398–410PubMed Gohlke-Barwolf C, Acar J, Burckhardt D, et al. Guidelines for prevention of thromboembolic events in valvular heart disease. Ad Hoc Committee of the Working Group on Valvular Heart Disease, European Society of Cardiology. J Heart Valve Dis 1993; 2: 398–410PubMed
62.
go back to reference Beyth RJ. Hemorrhagic complications of oral anticoagulant therapy. Clin Geriatr Med 2001; 17: 49–56PubMedCrossRef Beyth RJ. Hemorrhagic complications of oral anticoagulant therapy. Clin Geriatr Med 2001; 17: 49–56PubMedCrossRef
63.
go back to reference Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119: 108S–21SPubMedCrossRef Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119: 108S–21SPubMedCrossRef
64.
go back to reference Adams JN, Guatam PC. Warfarin therapy in the elderly. Br J Hosp Med 1994 Apr 20; 51: 392–3PubMed Adams JN, Guatam PC. Warfarin therapy in the elderly. Br J Hosp Med 1994 Apr 20; 51: 392–3PubMed
65.
go back to reference Khosla R, Butman AN, Hammer DF. Simvastatin-induced lupus erythematosus. South Med J 1998; 91: 873–4PubMedCrossRef Khosla R, Butman AN, Hammer DF. Simvastatin-induced lupus erythematosus. South Med J 1998; 91: 873–4PubMedCrossRef
66.
go back to reference Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet 2001 Mar 10; 357: 771–2PubMedCrossRef Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet 2001 Mar 10; 357: 771–2PubMedCrossRef
67.
go back to reference PATS (Post-Stroke Antihypertensive Treatment Study) Collaborating Group. Post-Stroke Antihypertensive Treatment Study. A preliminary result. Chin Med J (Engl) 1995; 108 (9): 710–7 PATS (Post-Stroke Antihypertensive Treatment Study) Collaborating Group. Post-Stroke Antihypertensive Treatment Study. A preliminary result. Chin Med J (Engl) 1995; 108 (9): 710–7
68.
go back to reference Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985 Jun 15; I: 1349–54CrossRef Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985 Jun 15; I: 1349–54CrossRef
69.
go back to reference Dahlof B, Lindholm LH, Hansson L, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991 Nov 23 338: 1281–5PubMedCrossRef Dahlof B, Lindholm LH, Hansson L, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991 Nov 23 338: 1281–5PubMedCrossRef
70.
go back to reference Medical Research Council. Trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992 Feb 15; 304: 405–12 Medical Research Council. Trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992 Feb 15; 304: 405–12
71.
go back to reference Lever AF, Ramsay LE. Treatment of hypertension in the elderly. J Hypertens 1995 Jun; 13 (6): 571–9 Lever AF, Ramsay LE. Treatment of hypertension in the elderly. J Hypertens 1995 Jun; 13 (6): 571–9
72.
go back to reference Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997 Sep 13; 350: 757–64PubMedCrossRef Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997 Sep 13; 350: 757–64PubMedCrossRef
73.
go back to reference Systolic Hypertension in the Elderly Program (SHEP). Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265: 3255–64 Systolic Hypertension in the Elderly Program (SHEP). Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265: 3255–64
74.
go back to reference Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease: Part 2. Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990 Apr 7 335: 827–38PubMedCrossRef Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease: Part 2. Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990 Apr 7 335: 827–38PubMedCrossRef
75.
go back to reference MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease: Part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990 Mar 31 335: 765–74PubMedCrossRef MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease: Part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990 Mar 31 335: 765–74PubMedCrossRef
76.
go back to reference Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998 Jun 13; 351(9118): 1755–62PubMedCrossRef Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998 Jun 13; 351(9118): 1755–62PubMedCrossRef
77.
go back to reference UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 1998; 317: 703–13 UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 1998; 317: 703–13
78.
go back to reference Gueyffier F, Boissel JP, Boutitie F, et al. Effect of antihypertensive treatment in patients having already suffered from stroke: gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators. Stroke 1997; 28: 2557–62PubMedCrossRef Gueyffier F, Boissel JP, Boutitie F, et al. Effect of antihypertensive treatment in patients having already suffered from stroke: gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators. Stroke 1997; 28: 2557–62PubMedCrossRef
79.
go back to reference Alsop K, Mac MM. Withdrawing cardiovascular medications at a syncope clinic. Postgrad Med J 2001; 77: 403–5PubMedCrossRef Alsop K, Mac MM. Withdrawing cardiovascular medications at a syncope clinic. Postgrad Med J 2001; 77: 403–5PubMedCrossRef
80.
go back to reference Duprez DA, De Buyzere ML, Clement DL. Calcium antagonists, is there a real concern about safety? Acta Clin Belg 1998; 53: 61–5PubMed Duprez DA, De Buyzere ML, Clement DL. Calcium antagonists, is there a real concern about safety? Acta Clin Belg 1998; 53: 61–5PubMed
81.
go back to reference Lindholm LH, Anderson H, Ekbom T, et al. Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension. 2: a 5-year, prospective, randomised, controlled trial. Lancet 2001 Aug 18; 358: 539–44PubMedCrossRef Lindholm LH, Anderson H, Ekbom T, et al. Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension. 2: a 5-year, prospective, randomised, controlled trial. Lancet 2001 Aug 18; 358: 539–44PubMedCrossRef
82.
go back to reference Pepine CJ. Improved endothelial function with angiotensin-converting enzyme inhibitors. Am J Cardiol 1997 Mar 6; 79: 29–32PubMedCrossRef Pepine CJ. Improved endothelial function with angiotensin-converting enzyme inhibitors. Am J Cardiol 1997 Mar 6; 79: 29–32PubMedCrossRef
83.
go back to reference Lonn E. Modifying the natural history of atherosclerosis: the SECURE trial. Int J Clin Pract Suppl 2001; 117: 13–8PubMed Lonn E. Modifying the natural history of atherosclerosis: the SECURE trial. Int J Clin Pract Suppl 2001; 117: 13–8PubMed
84.
go back to reference Schiffrin EL. Small artery remodeling in hypertension: can it be corrected? Am J Med Sci 2001; 322: 7–11PubMedCrossRef Schiffrin EL. Small artery remodeling in hypertension: can it be corrected? Am J Med Sci 2001; 322: 7–11PubMedCrossRef
85.
86.
go back to reference Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002 Mar 23 324: 699–701PubMedCrossRef Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002 Mar 23 324: 699–701PubMedCrossRef
87.
go back to reference Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000 Jan 20 342: 145–53PubMedCrossRef Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000 Jan 20 342: 145–53PubMedCrossRef
88.
go back to reference Carter AB. Hypotensive therapy in stroke survivors. Lancet 1970 Mar 7; I: 485–9CrossRef Carter AB. Hypotensive therapy in stroke survivors. Lancet 1970 Mar 7; I: 485–9CrossRef
89.
go back to reference Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974 Jul 22; 229: 409–18 Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974 Jul 22; 229: 409–18
90.
go back to reference Dutch Transient Ischemic Attack (TIA) Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. The Dutch TIA Trial Study Group. Stroke 1993; 24: 543–8 Dutch Transient Ischemic Attack (TIA) Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. The Dutch TIA Trial Study Group. Stroke 1993; 24: 543–8
91.
go back to reference Barer DH, Cruickshank JM, Ebrahim SB, et al. Low dose beta blockade in acute stroke (‘BEST’ trial): an evaluation. BMJ (Clin Res Ed) 1988 Mar 12 296: 737–41CrossRef Barer DH, Cruickshank JM, Ebrahim SB, et al. Low dose beta blockade in acute stroke (‘BEST’ trial): an evaluation. BMJ (Clin Res Ed) 1988 Mar 12 296: 737–41CrossRef
92.
go back to reference PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41 PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41
93.
go back to reference Vitovec J, Spinar J. First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Slovak Investigator Group. Eur J Heart Fail 2000; 2: 299–304PubMedCrossRef Vitovec J, Spinar J. First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Slovak Investigator Group. Eur J Heart Fail 2000; 2: 299–304PubMedCrossRef
94.
go back to reference Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the studies of left ventricular dysfunction (SOLVD). SOLVD Investigators. Am Heart J 1996 131: 350–5CrossRef Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the studies of left ventricular dysfunction (SOLVD). SOLVD Investigators. Am Heart J 1996 131: 350–5CrossRef
95.
go back to reference Wynckel A, Ebikili B, Melin JP, et al. Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors. Am J Hypertens 1998 11: 1080–6PubMedCrossRef Wynckel A, Ebikili B, Melin JP, et al. Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors. Am J Hypertens 1998 11: 1080–6PubMedCrossRef
96.
go back to reference Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 2000 Mar 13; 160: 685–93PubMedCrossRef Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 2000 Mar 13; 160: 685–93PubMedCrossRef
97.
go back to reference Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001 Apr 17 134: 629–36PubMed Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001 Apr 17 134: 629–36PubMed
98.
go back to reference Esmail ZN, Loewen PS. Losartan as an alternative to ACE inhibitors in patients with renal dysfunction. Ann Pharmacother 1998; 32: 1096–8PubMedCrossRef Esmail ZN, Loewen PS. Losartan as an alternative to ACE inhibitors in patients with renal dysfunction. Ann Pharmacother 1998; 32: 1096–8PubMedCrossRef
99.
go back to reference Stys T, Lawson WE, Smaldone GC, et al. Does aspirin attenuate the beneficial effects of angiotensin-converting enzyme inhibition in heart failure? Arch Intern Med 2000 May 22 160: 1409–13PubMedCrossRef Stys T, Lawson WE, Smaldone GC, et al. Does aspirin attenuate the beneficial effects of angiotensin-converting enzyme inhibition in heart failure? Arch Intern Med 2000 May 22 160: 1409–13PubMedCrossRef
100.
go back to reference Schrader J, Rothemeyer M, Luders S, et al. Hypertension and stroke: rationale behind the ACCESS trial. Acute Candesartan Cilexetil Evaluation in Stroke Survivors. Basic Res Cardiol 1998; 93Suppl. 2: 69–78PubMedCrossRef Schrader J, Rothemeyer M, Luders S, et al. Hypertension and stroke: rationale behind the ACCESS trial. Acute Candesartan Cilexetil Evaluation in Stroke Survivors. Basic Res Cardiol 1998; 93Suppl. 2: 69–78PubMedCrossRef
101.
go back to reference Oizilbash N, Duffy SW, Warlow C, et al. Lipids are risk factors for ischemic stroke overview and review. Cerebrovasc Dis 1992 2: 127–36CrossRef Oizilbash N, Duffy SW, Warlow C, et al. Lipids are risk factors for ischemic stroke overview and review. Cerebrovasc Dis 1992 2: 127–36CrossRef
102.
go back to reference National Cholesterol Education Program (NCEP). Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269: 3015–3023 National Cholesterol Education Program (NCEP). Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269: 3015–3023
103.
go back to reference Fine-Edelstein JS, Wolf PA, O’Leary DH, et al. Precursors of extracranial carotid atherosclerosis in the Framingham Study. Neurology 1994 44: 1046–50PubMedCrossRef Fine-Edelstein JS, Wolf PA, O’Leary DH, et al. Precursors of extracranial carotid atherosclerosis in the Framingham Study. Neurology 1994 44: 1046–50PubMedCrossRef
104.
go back to reference Blauw GJ, Lagaay AM, Smelt AH, et al. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 1997 28: 946–50PubMedCrossRef Blauw GJ, Lagaay AM, Smelt AH, et al. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 1997 28: 946–50PubMedCrossRef
105.
go back to reference Crouse III JR, Byington RP, Hoen HM, et al. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med 1997 Jun 23 157: 1305–10PubMedCrossRef Crouse III JR, Byington RP, Hoen HM, et al. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med 1997 Jun 23 157: 1305–10PubMedCrossRef
106.
go back to reference Plehn JF, Davis BR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the cholesterol and recurrent events (CARE) study. Circulation 1999 Jan 19 99: 216–23PubMedCrossRef Plehn JF, Davis BR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the cholesterol and recurrent events (CARE) study. Circulation 1999 Jan 19 99: 216–23PubMedCrossRef
107.
go back to reference White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000 Aug 3 343: 317–26PubMedCrossRef White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000 Aug 3 343: 317–26PubMedCrossRef
108.
go back to reference Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20: 1460–5PubMedCrossRef Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20: 1460–5PubMedCrossRef
109.
go back to reference MRC/BHF Heart Protection Study. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002; 360 (9326): 7–22 MRC/BHF Heart Protection Study. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002; 360 (9326): 7–22
110.
go back to reference MRC/BHF Heart Protection Study. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals. Lancet 2002; 360 (9326): 23–33 MRC/BHF Heart Protection Study. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals. Lancet 2002; 360 (9326): 23–33
111.
go back to reference Callahan A. Cerebrovascular disease and statins: a potential addition to the therapeutic armamentarium for stroke prevention. Am J Cardiol 2001 Oct 11; 88: 33J–7JPubMedCrossRef Callahan A. Cerebrovascular disease and statins: a potential addition to the therapeutic armamentarium for stroke prevention. Am J Cardiol 2001 Oct 11; 88: 33J–7JPubMedCrossRef
112.
go back to reference Davidson MH. Safety profiles for the HMG-CoA reductase inhibitors: treatment and trust. Drugs 2001; 61(2): 197–206PubMedCrossRef Davidson MH. Safety profiles for the HMG-CoA reductase inhibitors: treatment and trust. Drugs 2001; 61(2): 197–206PubMedCrossRef
113.
go back to reference Davidson MH, Stein EA, Hunninghake DB, et al. Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia. Nutr Metab Cardiovasc Dis 2000 10: 253–62PubMed Davidson MH, Stein EA, Hunninghake DB, et al. Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia. Nutr Metab Cardiovasc Dis 2000 10: 253–62PubMed
114.
go back to reference Cilla Jr DD, Whitfield LR, Gibson DM, et al. Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Clin Pharmacol Ther 1996 60: 687–95PubMedCrossRef Cilla Jr DD, Whitfield LR, Gibson DM, et al. Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Clin Pharmacol Ther 1996 60: 687–95PubMedCrossRef
115.
go back to reference Atkins D, Psaty BM, Koepsell TD, et al. Cholesterol reduction and the risk for stroke in men: a meta-analysis of randomized, controlled trials. Ann Intern Med 1993 Jul 15 119: 136–45PubMed Atkins D, Psaty BM, Koepsell TD, et al. Cholesterol reduction and the risk for stroke in men: a meta-analysis of randomized, controlled trials. Ann Intern Med 1993 Jul 15 119: 136–45PubMed
116.
go back to reference Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989 Mar 25; 298: 789–94PubMedCrossRef Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989 Mar 25; 298: 789–94PubMedCrossRef
117.
go back to reference Wannamethee SG, Shaper AG, Whincup PH, et al. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995 Jul 12 274: 155–60PubMedCrossRef Wannamethee SG, Shaper AG, Whincup PH, et al. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995 Jul 12 274: 155–60PubMedCrossRef
118.
go back to reference Coleman T. Smoking cessation: integrating recent advances into clinical practice. Thorax 2001; 56: 579–82PubMedCrossRef Coleman T. Smoking cessation: integrating recent advances into clinical practice. Thorax 2001; 56: 579–82PubMedCrossRef
119.
go back to reference Dale LC, Glover ED, Sachs DP, et al. Bupropion for smoking cessation: predictors of successful outcome. Chest 2001 119: 1357–64PubMedCrossRef Dale LC, Glover ED, Sachs DP, et al. Bupropion for smoking cessation: predictors of successful outcome. Chest 2001 119: 1357–64PubMedCrossRef
120.
go back to reference Gonzales DH, Nides MA, Ferry LH, et al. Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study. Clin Pharmacol Ther 2001 69: 438–44PubMedCrossRef Gonzales DH, Nides MA, Ferry LH, et al. Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study. Clin Pharmacol Ther 2001 69: 438–44PubMedCrossRef
121.
go back to reference Enns MW. Seizure during combination of trimipramine and bupropion. J Clin Psychiatry 2001; 62: 476–7PubMedCrossRef Enns MW. Seizure during combination of trimipramine and bupropion. J Clin Psychiatry 2001; 62: 476–7PubMedCrossRef
122.
go back to reference Pederson KJ, Kuntz DH, Garbe GJ. Acute myocardial ischemia associated with ingestion of bupropion and pseudoephedrine in a 21-year-old man. Can J Cardiol 2001; 17: 599–601PubMed Pederson KJ, Kuntz DH, Garbe GJ. Acute myocardial ischemia associated with ingestion of bupropion and pseudoephedrine in a 21-year-old man. Can J Cardiol 2001; 17: 599–601PubMed
123.
go back to reference Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust 2001 Jun 18; 174: 650–1PubMed Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust 2001 Jun 18; 174: 650–1PubMed
124.
go back to reference Diabetes Control and Complications Trial. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995 May 1; 75: 894–903 Diabetes Control and Complications Trial. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995 May 1; 75: 894–903
125.
go back to reference UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 Sep 12; 352: 837–53 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 Sep 12; 352: 837–53
126.
go back to reference American College of Physicians. Guidelines for medical treatment for stroke prevention. American College of Physicians. Ann Intern Med 1994 Jul 1; 121: 54–5 American College of Physicians. Guidelines for medical treatment for stroke prevention. American College of Physicians. Ann Intern Med 1994 Jul 1; 121: 54–5
127.
go back to reference Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–97 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–97
Metadata
Title
A Benefit-Risk Assessment of Agents Used in the Secondary Prevention of Stroke
Authors
Dr Ronald S. MacWalter
Colin P. Shirley
Publication date
01-11-2002
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 13/2002
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200225130-00005

Other articles of this Issue 13/2002

Drug Safety 13/2002 Go to the issue