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

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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.

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References

  1. 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: 1684–91

    Article  PubMed  CAS  Google Scholar 

  2. Caro JJ, Huybrechts KF. Stroke treatment economic model (STEM): predicting long-term costs from functional status. Stroke 1999; 30: 2574–9

    Article  PubMed  CAS  Google Scholar 

  3. Terent A. Stroke morbidity in stroke: populations, cohorts, and clinical trials. Oxford: Butterworth-Heineman, 1993

    Google Scholar 

  4. Dyken ML, Pokras R. The performance of endarterectomy for disease of the extracranial arteries of the head. Stroke 1984; 15: 948–50

    Article  PubMed  CAS  Google Scholar 

  5. Wolf PA, D’Agostino RB, O’Neal MA, et al. Secular trends in stroke incidence and mortality. The Framingham Study. Stroke 1992 23: 1551–5

    Article  CAS  Google Scholar 

  6. Department of Health. Health of the Nation: a strategy for health in England. London: HMSO, 1992

  7. 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

    Google Scholar 

  8. Dunbabin D. Cost-effective intervention in stroke. Pharmacoeconomics 1992; 2: 468–99

    Article  PubMed  CAS  Google Scholar 

  9. Ramasubbu R. Relationship between depression and cerebrovascular disease: conceptual issues. J Affect Disord 2000; 57: 1–11

    Article  PubMed  CAS  Google Scholar 

  10. 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. Warner TD. Relationships between the endothelin and nitric oxide pathways. Clin Exp Pharmacol Physiol 1999; 26: 247–52

    Article  PubMed  CAS  Google Scholar 

  12. 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. 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. 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. 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. 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

    Google Scholar 

  17. 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: 1044–54

    Article  PubMed  CAS  Google Scholar 

  18. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000 Nov 11; 321: 1183–7

    Article  PubMed  CAS  Google Scholar 

  19. 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: 171–81

    Article  PubMed  CAS  Google Scholar 

  20. Hawkey CJ. Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs. Gut 2000; 46: 310–1h

    Article  PubMed  CAS  Google Scholar 

  21. 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: 779–86

    Article  PubMed  CAS  Google Scholar 

  22. Barnett HJ, Eliasziw M, Meldrum HE. Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995 Jan 26; 332: 238–48

    Article  PubMed  CAS  Google Scholar 

  23. Algra A, van Gijn J. Aspirin at any dose above 30mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 1996; 60: 197–9

    Article  PubMed  CAS  Google Scholar 

  24. Barnett HJ, Kaste M, Meldrum H, et al. Aspirin dose in stroke prevention: beautiful hypotheses slain by ugly facts. Stroke 1996; 27: 588–92

    Article  PubMed  CAS  Google Scholar 

  25. 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: 2337–42

    Article  PubMed  CAS  Google Scholar 

  26. Helgason CM, Bolin KM, Hoff JA, et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994 25: 2331–6

    Article  PubMed  CAS  Google Scholar 

  27. McGeehan M, Bush RK. The mechanisms of aspirin-intolerant asthma and its management. Curr Allergy Asthma Rep 2002; 2: 117–25

    Article  PubMed  Google Scholar 

  28. 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

    CAS  Google Scholar 

  29. Boysen G. Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit-risk analysis. J Intern Med 1999; 246: 239–45

    Article  PubMed  CAS  Google Scholar 

  30. 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: 1809–17

    Article  PubMed  CAS  Google Scholar 

  31. 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: 1650–5

    Article  PubMed  CAS  Google Scholar 

  32. Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 1998; 114: 470S–88S

    Article  PubMed  CAS  Google Scholar 

  33. 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: 5–14

    Article  PubMed  CAS  Google Scholar 

  34. 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

    CAS  Google Scholar 

  35. 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: 1–13

    Article  PubMed  CAS  Google Scholar 

  36. 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: 179–86

    Article  PubMed  CAS  Google Scholar 

  37. Virtanen KS, Mattila S, Jarvinen A, et al. Angiographic findings in patients exhibiting ischemia after oral dipyridamole. Int J Cardiol 1989 23: 33–6

    Article  PubMed  CAS  Google Scholar 

  38. Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989 Jun 3 I: 1215–20

    Article  Google Scholar 

  39. 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: 501–7

    Article  PubMed  CAS  Google Scholar 

  40. 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. 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): 325–35

    Article  PubMed  CAS  Google Scholar 

  42. Trontell AE, Honig PK. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–2

    Article  PubMed  CAS  Google Scholar 

  43. Salliere D, Kassler-Taub KB. Clopidogrel and thrombotic thrombocytopenic purpura. N Engl J Med 2000 Oct 19; 343: 1191–4

    Article  PubMed  CAS  Google Scholar 

  44. 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: 1444–51

    Article  PubMed  CAS  Google Scholar 

  45. 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: 147–50

    Article  PubMed  Google Scholar 

  46. Diener HC, Ringleb P. Antithrombotic secondary prevention after stroke. 2001; 3: 451–62

    Google Scholar 

  47. Rho R, DeNofrio D, Loh E. Cardiomyopathy and embolization: risks and benefits of anticoagulation in sinus rhythm. Curr Cardiol Rep 2000; 2: 106–11

    Article  PubMed  CAS  Google Scholar 

  48. Stein PD, Alpert JS, Bussey HI, et al. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001 119: 220S–7S

    Article  PubMed  CAS  Google Scholar 

  49. Lowe GD, Jaap AJ, Forbes CD. Relation of atrial fibrillation and high haematocrit tomortality in acute stroke. Lancet 1983 Apr 9; I: 784–6

    Article  Google Scholar 

  50. 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: 1460–5

    Article  PubMed  CAS  Google Scholar 

  51. 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. 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. 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: 492–501

    PubMed  CAS  Google Scholar 

  54. 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. 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. Consensus Conference on Atrial Fibrillation. Consensus conference on atrial fibrillation in hospital and general practice. Scott Med J 1998; 43: 166–7

    Google Scholar 

  57. Laupacis A, Albers G, Dalen J, et al. Antithrombotic therapy in atrial fibrillation. Chest 1995 108: 352S–9S

    Article  PubMed  CAS  Google Scholar 

  58. 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

    Google Scholar 

  59. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8

    Article  PubMed  CAS  Google Scholar 

  60. Levine HJ, Pauker SG, Eckman MH. Antithrombotic therapy in valvular heart disease. Chest 1995; 108: 360S–70S

    Article  PubMed  CAS  Google Scholar 

  61. 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: 398–410

    PubMed  CAS  Google Scholar 

  62. Beyth RJ. Hemorrhagic complications of oral anticoagulant therapy. Clin Geriatr Med 2001; 17: 49–56

    Article  PubMed  CAS  Google Scholar 

  63. Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119: 108S–21S

    Article  PubMed  CAS  Google Scholar 

  64. Adams JN, Guatam PC. Warfarin therapy in the elderly. Br J Hosp Med 1994 Apr 20; 51: 392–3

    PubMed  CAS  Google Scholar 

  65. Khosla R, Butman AN, Hammer DF. Simvastatin-induced lupus erythematosus. South Med J 1998; 91: 873–4

    Article  PubMed  CAS  Google Scholar 

  66. Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet 2001 Mar 10; 357: 771–2

    Article  PubMed  CAS  Google Scholar 

  67. 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

    Google Scholar 

  68. 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: 1349–54

    Article  Google Scholar 

  69. 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: 1281–5

    Article  PubMed  CAS  Google Scholar 

  70. Medical Research Council. Trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992 Feb 15; 304: 405–12

  71. Lever AF, Ramsay LE. Treatment of hypertension in the elderly. J Hypertens 1995 Jun; 13 (6): 571–9

    Google Scholar 

  72. 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: 757–64

    Article  PubMed  CAS  Google Scholar 

  73. 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

    Google Scholar 

  74. 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: 827–38

    Article  PubMed  CAS  Google Scholar 

  75. 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: 765–74

    Article  PubMed  CAS  Google Scholar 

  76. 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): 1755–62

    Article  PubMed  CAS  Google Scholar 

  77. UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 1998; 317: 703–13

    Google Scholar 

  78. 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: 2557–62

    Article  PubMed  CAS  Google Scholar 

  79. Alsop K, Mac MM. Withdrawing cardiovascular medications at a syncope clinic. Postgrad Med J 2001; 77: 403–5

    Article  PubMed  CAS  Google Scholar 

  80. Duprez DA, De Buyzere ML, Clement DL. Calcium antagonists, is there a real concern about safety? Acta Clin Belg 1998; 53: 61–5

    PubMed  CAS  Google Scholar 

  81. 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: 539–44

    Article  PubMed  CAS  Google Scholar 

  82. Pepine CJ. Improved endothelial function with angiotensin-converting enzyme inhibitors. Am J Cardiol 1997 Mar 6; 79: 29–32

    Article  PubMed  CAS  Google Scholar 

  83. Lonn E. Modifying the natural history of atherosclerosis: the SECURE trial. Int J Clin Pract Suppl 2001; 117: 13–8

    PubMed  Google Scholar 

  84. Schiffrin EL. Small artery remodeling in hypertension: can it be corrected? Am J Med Sci 2001; 322: 7–11

    Article  PubMed  CAS  Google Scholar 

  85. Bargout R. The HOPE study [letter]. Cleve Clin J Med 2000; 67: 452

    PubMed  CAS  Google Scholar 

  86. Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002 Mar 23 324: 699–701

    Article  PubMed  CAS  Google Scholar 

  87. 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: 145–53

    Article  PubMed  CAS  Google Scholar 

  88. Carter AB. Hypotensive therapy in stroke survivors. Lancet 1970 Mar 7; I: 485–9

    Article  Google Scholar 

  89. 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. 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

    Google Scholar 

  91. 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: 737–41

    Article  CAS  Google Scholar 

  92. 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

    Google Scholar 

  93. 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: 299–304

    Article  PubMed  CAS  Google Scholar 

  94. 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: 350–5

    Article  CAS  Google Scholar 

  95. 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: 1080–6

    Article  PubMed  CAS  Google Scholar 

  96. 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: 685–93

    Article  PubMed  CAS  Google Scholar 

  97. 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: 629–36

    PubMed  CAS  Google Scholar 

  98. Esmail ZN, Loewen PS. Losartan as an alternative to ACE inhibitors in patients with renal dysfunction. Ann Pharmacother 1998; 32: 1096–8

    Article  PubMed  CAS  Google Scholar 

  99. 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: 1409–13

    Article  PubMed  CAS  Google Scholar 

  100. 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: 69–78

    Article  PubMed  Google Scholar 

  101. Oizilbash N, Duffy SW, Warlow C, et al. Lipids are risk factors for ischemic stroke overview and review. Cerebrovasc Dis 1992 2: 127–36

    Article  Google Scholar 

  102. 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

    Google Scholar 

  103. Fine-Edelstein JS, Wolf PA, O’Leary DH, et al. Precursors of extracranial carotid atherosclerosis in the Framingham Study. Neurology 1994 44: 1046–50

    Article  PubMed  CAS  Google Scholar 

  104. 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: 946–50

    Article  PubMed  CAS  Google Scholar 

  105. Crouse III JR, Byington RP, Hoen HM, et al. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med 1997 Jun 23 157: 1305–10

    Article  PubMed  CAS  Google Scholar 

  106. 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: 216–23

    Article  PubMed  CAS  Google Scholar 

  107. White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000 Aug 3 343: 317–26

    Article  PubMed  CAS  Google Scholar 

  108. Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20: 1460–5

    Article  PubMed  CAS  Google Scholar 

  109. 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

    Google Scholar 

  110. 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

    Google Scholar 

  111. Callahan A. Cerebrovascular disease and statins: a potential addition to the therapeutic armamentarium for stroke prevention. Am J Cardiol 2001 Oct 11; 88: 33J–7J

    Article  PubMed  CAS  Google Scholar 

  112. Davidson MH. Safety profiles for the HMG-CoA reductase inhibitors: treatment and trust. Drugs 2001; 61(2): 197–206

    Article  PubMed  CAS  Google Scholar 

  113. 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: 253–62

    PubMed  CAS  Google Scholar 

  114. 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: 687–95

    Article  PubMed  CAS  Google Scholar 

  115. 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: 136–45

    PubMed  CAS  Google Scholar 

  116. Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989 Mar 25; 298: 789–94

    Article  PubMed  CAS  Google Scholar 

  117. Wannamethee SG, Shaper AG, Whincup PH, et al. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995 Jul 12 274: 155–60

    Article  PubMed  CAS  Google Scholar 

  118. Coleman T. Smoking cessation: integrating recent advances into clinical practice. Thorax 2001; 56: 579–82

    Article  PubMed  CAS  Google Scholar 

  119. Dale LC, Glover ED, Sachs DP, et al. Bupropion for smoking cessation: predictors of successful outcome. Chest 2001 119: 1357–64

    Article  PubMed  CAS  Google Scholar 

  120. 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: 438–44

    Article  PubMed  CAS  Google Scholar 

  121. Enns MW. Seizure during combination of trimipramine and bupropion. J Clin Psychiatry 2001; 62: 476–7

    Article  PubMed  CAS  Google Scholar 

  122. 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: 599–601

    PubMed  CAS  Google Scholar 

  123. Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust 2001 Jun 18; 174: 650–1

    PubMed  CAS  Google Scholar 

  124. 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

    Google Scholar 

  125. 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

    Google Scholar 

  126. American College of Physicians. Guidelines for medical treatment for stroke prevention. American College of Physicians. Ann Intern Med 1994 Jul 1; 121: 54–5

    Google Scholar 

  127. 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

    Google Scholar 

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Acknowledgements

We acknowledge the support of colleagues in Ninewells Hospital & Medical School, Dundee, Tayside University Hospitals Trust and University of Dundee, Scotland, UK. RSM has received educational grants from Boehringer Ingelheim, Sanofi-Synthelabo, Napp and other pharmaceutical companies. He has lectured to other members of the medical profession for many pharmaceutical companies including Boehringer Ingelheim, Sanofi-Synthelabo, Pfizer, Servier, MSD and AstraZeneca. This manuscript was not funded by any source.

We acknowledge the PROGRESS (Perindopril Prevention Against Recurrent Stroke Study) group and Dr Neil Chapman, Senior Research Fellow, Institute of International Health, University of Sydney, Australia, for their kind permission to reproduce part of their slide set. References

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  1. The Stroke Study Centre, University Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom

    Ronald S. MacWalter & Colin P. Shirley

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  1. Ronald S. MacWalter
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  2. Colin P. Shirley
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Correspondence to Ronald S. MacWalter.

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MacWalter, R.S., Shirley, C.P. A Benefit-Risk Assessment of Agents Used in the Secondary Prevention of Stroke. Drug-Safety 25, 943–963 (2002). https://doi.org/10.2165/00002018-200225130-00005

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