Antiplatelet therapy in ischemic stroke: Variability in clinical trials and its impact on choosing the appropriate therapy

Journal of the Neurological Sciences

Volumn 284, Issue 1-2, 2009, Pages 1-9

  Biller, José ^a  

^a LOYOLA UNIVERSITY CHICAGO   (United States)

Author keywords

Antiplatelet therapy; Aspirin; Clopidogrel; Dipyridamole; Ischemic stroke; Randomized clinical trials

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; DIPYRIDAMOLE; SIMVASTATIN;

BLEEDING; BRAIN HEMORRHAGE; CEREBROVASCULAR ACCIDENT; CLINICAL DECISION MAKING; CLINICAL TRIAL; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; EVIDENCE BASED MEDICINE; GASTROINTESTINAL HEMORRHAGE; HEADACHE; HIGH RISK PATIENT; HUMAN; LOADING DRUG DOSE; MONOTHERAPY; PEPTIC ULCER BLEEDING; PRACTICE GUIDELINE; PRIORITY JOURNAL; RECURRENCE RISK; REVIEW; STROKE PATIENT; TRANSIENT ISCHEMIC ATTACK; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ASPIRIN; ATHEROSCLEROSIS; BRAIN ISCHEMIA; CLINICAL TRIALS AS TOPIC; CONFOUNDING FACTORS (EPIDEMIOLOGY); DECISION MAKING; DIPYRIDAMOLE; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; EVIDENCE-BASED MEDICINE; FEMALE; FOLLOW-UP STUDIES; HEMORRHAGE; HUMANS; ISCHEMIC ATTACK, TRANSIENT; MALE; MIDDLE AGED; MULTICENTER STUDIES AS TOPIC; PATIENT SELECTION; PLATELET AGGREGATION INHIBITORS; RECURRENCE; RESEARCH DESIGN; TICLOPIDINE;

EID: 67949117129     PISSN: 0022510X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jns.2009.04.001     Document Type: Review

References (86)

1. Rosamond W., Flegal K., Furie K., et al. Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117 4 (2008) e25-e146
2. Steg P.G., Bhatt D.L., Wilson P.W., et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 297 11 (2007) 1197-1206
3. Vickrey B.G., Rector T.S., Wickstrom S.L., et al. Occurrence of secondary ischemic events among persons with atherosclerotic vascular disease. Stroke 33 4 (2002) 901-906
4. Burn J., Dennis M., Bamford J., Sandercock P., Wade D., and Warlow C. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 25 2 (1994) 333-337
5. Hankey G.J., Jamrozik K., Broadhurst R.J., et al. Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke 29 12 (1998) 2491-2500
6. Hardie K., Hankey G.J., Jamrozik K., Broadhurst R.J., and Anderson C. Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study. Stroke 35 3 (2004) 731-735
7. Dhamoon M.S., Tai W., Boden-Albala B., et al. Risk of myocardial infarction or vascular death after first ischemic stroke: the Northern Manhattan Study. Stroke 38 6 (2007) 1752-1758
8. Algra A., and van Gijn J. Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 60 2 (1996) 197-199
9. McQuaid K.R., and Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 119 8 (2006) 624-638
10. Diener H.C., Cunha L., Forbes C., Sivenius J., Smets P., and Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 143 1-2 (1996) 1-13
11. Halkes P.H., van Gijn J., Kappelle L.J., Koudstaal P.J., and Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 367 9523 (2006) 1665-1673
12. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348 9038 (1996) 1329-1339
13. Diener H.C., Bogousslavsky J., Brass L.M., et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 364 9431 (2004) 331-337
14. Bhatt D.L., Fox K.A., Hacke W., et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 354 16 (2006) 1706-1717
15. Bhatt D.L., Flather M.D., Hacke W., et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 49 19 (2007) 1982-1988
16. Adams R.J., Albers G., Alberts M.J., et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 39 5 (2008) 1647-1652
17. Albers G.W., Amarenco P., Easton J.D., Sacco R.L., and Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133 6 Suppl (2008) 630S-669S
18. Kent D.M., and Thaler D.E. Stroke prevention - insights from incoherence. N Engl J Med 359 12 (2008) 1287-1289
19. Thijs V., Lemmens R., and Fieuws S. Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J 29 9 (2008) 1086-1092
20. Jonas S., and Grieco G. Potential value of triple antiplatelet therapy for secondary stroke prevention. Stroke 34 10 (2003) e182-e183
21. Willmot M., Zhao L., Heptinstall S., and Bath P. Triple antiplatelet therapy for secondary prevention of recurrent ischemic stroke. J Stroke Cerebrovasc Dis 13 3 (2004) 138-140
22. Sacco R.L., Diener H.C., Yusuf S., et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med (2008)
23. Sprigg N., Gray L.J., England T., et al. A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility. PLoS ONE 3 8 (2008) e2852
24. Adams Jr. H.P., Bendixen B.H., Kappelle L.J., et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24 1 (1993) 35-41
25. Bamford J., Sandercock P., Dennis M., et al. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981-86. 1. Methodology, demography and incident cases of first-ever stroke. J Neurol Neurosurg Psychiatry 51 11 (1988) 1373-1380
26. Kunitz S.C., Gross C.R., Heyman A., et al. The pilot Stroke Data Bank: definition, design, and data. Stroke 15 4 (1984) 740-746
27. Sacco R.L., Adams R., Albers G., et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Circulation 113 10 (2006) e409-e449
28. Petty G.W., Brown Jr. R.D., Whisnant J.P., Sicks J.D., O'Fallon W.M., and Wiebers D.O. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 31 5 (2000) 1062-1068
29. de Jong G., van Raak L., Kessels F., and Lodder J. Stroke subtype and mortality. A follow-up study in 998 patients with a first cerebral infarct. J Clin Epidemiol 56 3 (2003) 262-268
30. Grau A.J., Weimar C., Buggle F., et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 32 11 (2001) 2559-2566
31. Lovett J.K., Coull A.J., and Rothwell P.M. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology 62 4 (2004) 569-573
32. Fan Y.H., Mok V.C., Lam W.W., Hui A.C., and Wong K.S. Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts. J Neurol 251 5 (2004) 537-541
33. Fan Y.H., Zhang L., Lam W.W., Mok V.C., and Wong K.S. Cerebral microbleeds as a risk factor for subsequent intracerebral hemorrhages among patients with acute ischemic stroke. Stroke 34 10 (2003) 2459-2462
34. Kato H., Izumiyama M., Izumiyama K., Takahashi A., and Itoyama Y. Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke 33 6 (2002) 1536-1540
35. Koennecke H.C. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology 66 2 (2006) 165-171
36. Naka H., Nomura E., Wakabayashi S., et al. Frequency of asymptomatic microbleeds on T2*-weighted MR images of patients with recurrent stroke: association with combination of stroke subtypes and leukoaraiosis. AJNR Am J Neuroradiol 25 5 (2004) 714-719
37. Petty G.W., Brown Jr. R.D., Whisnant J.P., Sicks J.D., O'Fallon W.M., and Wiebers D.O. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 30 12 (1999) 2513-2516
38. Vemmos K.N., Bots M.L., Tsibouris P.K., et al. Prognosis of stroke in the south of Greece: 1 year mortality, functional outcome and its determinants: the Arcadia Stroke Registry. J Neurol Neurosurg Psychiatry 69 5 (2000) 595-600
39. Elneihoum A.M., Goransson M., Falke P., and Janzon L. Three-year survival and recurrence after stroke in Malmo, Sweden: an analysis of stroke registry data. Stroke 29 10 (1998) 2114-2117
40. Appelros P., Nydevik I., and Viitanen M. Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year. Stroke 34 1 (2003) 122-126
41. Bhatt D.L., Steg P.G., Ohman E.M., et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 295 2 (2006) 180-189
42. Petty G.W., Brown Jr. R.D., Whisnant J.P., Sicks J.D., O'Fallon W.M., and Wiebers D.O. Survival and recurrence after first cerebral infarction: a population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 50 1 (1998) 208-216
43. Saposnik G., Hill M.D., O'Donnell M., Fang J., Hachinski V., and Kapral M.K. Variables associated with 7-day, 30-day, and 1-year fatality after ischemic stroke. Stroke (2008)
44. Broessner G., Helbok R., Lackner P., et al. Survival and long-term functional outcome in 1,155 consecutive neurocritical care patients. Crit Care Med 35 9 (2007) 2025-2030
45. Acciarresi M., Caso V., Venti M., et al. First-ever stroke and outcome in patients admitted to Perugia Stroke Unit: predictors for death, dependency, and recurrence of stroke within the first three months. Clin Exp Hypertens 28 3-4 (2006) 287-294
46. Kitamura A., Nakagawa Y., Sato M., et al. Proportions of stroke subtypes among men and women > or = 40 years of age in an urban Japanese city in 1992, 1997, and 2002. Stroke 37 6 (2006) 1374-1378
47. Ohira T., Shahar E., Chambless L.E., Rosamond W.D., Mosley Jr. T.H., and Folsom A.R. Risk factors for ischemic stroke subtypes: the Atherosclerosis Risk in Communities study. Stroke 37 10 (2006) 2493-2498
48. Shin D.H., Lee P.H., and Bang O.Y. Mechanisms of recurrence in subtypes of ischemic stroke: a hospital-based follow-up study. Arch Neurol 62 8 (2005) 1232-1237
49. Li H., and Wong K.S. Racial distribution of intracranial and extracranial atherosclerosis. J Clin Neurosci 10 1 (2003) 30-34
50. Sacco R.L., Kargman D.E., Gu Q., and Zamanillo M.C. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 26 1 (1995) 14-20
51. Algra A., and van Gijn J. Science unblinded. Lancet 343 8904 (1994) 1040
52. Schulz K.F., Chalmers I., and Altman D.G. The landscape and lexicon of blinding in randomized trials. Ann Intern Med 136 3 (2002) 254-259
53. Diener H.C., Sacco R., and Yusuf S. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). Cerebrovasc Dis 23 5-6 (2007) 368-380
54. Piaggio G., Elbourne D.R., Altman D.G., Pocock S.J., and Evans S.J. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 295 10 (2006) 1152-1160
55. Albers G.W. Choice of endpoints in antiplatelet trials: which outcomes are most relevant to stroke patients?. Neurology 54 5 (2000) 1022-1028
56. Coull A.J., Lovett J.K., and Rothwell P.M. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ 328 7435 (2004) 326
57. Kennedy J., Hill M.D., Ryckborst K.J., Eliasziw M., Demchuk A.M., and Buchan A.M. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 6 11 (2007) 961-969
58. 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 324 7329 (2002) 71-86
59. Serebruany V.L., Malinin A.I., Eisert R.M., and Sane D.C. Risk of bleeding complications with antiplatelet agents: meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials. Am J Hematol 75 1 (2004) 40-47
60. Akinboboye O.O., Idris O., Chou R.L., Sciacca R.R., Cannon P.J., and Bergmann S.R. Absolute quantitation of coronary steal induced by intravenous dipyridamole. J Am Coll Cardiol 37 1 (2001) 109-116
61. Jagathesan R., Rosen S.D., Foale R.A., Camici P.G., and Picano E. Effects of long-term oral dipyridamole treatment on coronary microcirculatory function in patients with chronic stable angina: A substudy of the persantine in stable angina (PISA) study. J Cardiovasc Pharmacol 48 3 (2006) 110-116
62. Virtanen K.S., Mattila S., Jarvinen A., and Frick M.H. Angiographic findings in patients exhibiting ischemia after oral dipyridamole. Int J Cardiol 23 1 (1989) 33-36
63. De Schryver E.L., Algra A., and van Gijn J. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. An update. Stroke (2008)
64. Bowry A.D., Brookhart M.A., and Choudhry N.K. Meta-analysis of the efficacy and safety of clopidogrel plus aspirin as compared to antiplatelet monotherapy for the prevention of vascular events. Am J Cardiol 101 7 (2008) 960-966
65. Chen K.-Y., Rha S.-W., Li Y.-J., et al. Triple versus dual antiplatelet therapy in diabetic patients with acute myocardial infarction undergoing percutaneous coronary intervention in the era of drug-eluting stent. Presented at the Transcatheter Cardiovascular Therapeutics Scientific Symposium, October 12-17, 2008, Washington, DC (2008)
66. Lee S.W., Park S.W., Kim Y.H., et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients). J Am Coll Cardiol 51 12 (2008) 1181-1187
67. Passero S., Ciacci G., and Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 61 10 (2003) 1351-1356
68. Kase C.S., Furlan A.J., Wechsler L.R., et al. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology 57 9 (2001) 1603-1610
69. Bhatt D.L., Scheiman J., Abraham N.S., et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation (2008)
70. Lai K.C., Chu K.M., Hui W.M., et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol 4 7 (2006) 860-865
71. Chan F.K., Ching J.Y., Hung L.C., et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 352 3 (2005) 238-244
72. Ng F.H., Wong B.C., Wong S.Y., Chen W.H., and Chang C.M. Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin-induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re-bleeding risk - a single-blind, randomized controlled study. Aliment Pharmacol Ther 19 3 (2004) 359-365
73. Gilard M., Arnaud B., Cornily J.C., et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 51 3 (2008) 256-260
74. Zairis M., Patsourakos N., and Makrygiannis C. The impact of oral proton pump inhibitors on the effectiveness of combined aspirin and clopidogrel drug therapy during the first year after elective coronary stenting. Abstracts of the European Society of Cardiology Congress 2008. Munich, Germany. August 30-September 3, 2008. Eur Heart J 29 Suppl 1 (2008) 3-900
75. Siller-Matula J.M., Spiel A.O., Lang I.M., Kreiner G., Christ G., Jilma B., et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 157 1 (2009) 148.e1-148.e5
76. Mega J.L., Close S.L., Wiviott S.D., et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360 4 (2009) 354-362
77. Biller J. Aspirin nonresponse in patients with arterial causes of ischemic stroke: considerations in detection and management. J Neurol Sci 272 1-2 (2008) 1-7
78. Shireman T.I., Mahnken J.D., Howard P.A., Kresowik T.F., Hou Q., and Ellerbeck E.F. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 130 5 (2006) 1390-1396
79. Hart R.G., Tonarelli S.B., and Pearce L.A. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 36 7 (2005) 1588-1593
80. Caso V., Paciaroni M., Venti M., et al. Effect of on-admission antiplatelet treatment on patients with cerebral hemorrhage. Cerebrovasc Dis 24 2-3 (2007) 215-218
81. Treating Heart Disease, Heart Attack, and Stroke: The Antiplatelet Drugs. Comparing Effectiveness, Safety, and Price. Consumer Reports Best Buy Drugs: Consumer Reports (2007)
82. Levine D.A., Kiefe C.I., Howard G., Howard V.J., Williams O.D., and Allison J.J. Reduced medication access: a marker for vulnerability in US stroke survivors. Stroke 38 5 (2007) 1557-1564
83. Federman A.D., Adams A.S., Ross-Degnan D., Soumerai S.B., and Ayanian J.Z. Supplemental insurance and use of effective cardiovascular drugs among elderly medicare beneficiaries with coronary heart disease. JAMA 286 14 (2001) 1732-1739
84. Soumerai S.B., Pierre-Jacques M., Zhang F., et al. Cost-related medication nonadherence among elderly and disabled medicare beneficiaries: a national survey 1 year before the medicare drug benefit. Arch Intern Med 166 17 (2006) 1829-1835
85. Matchar D.B., Samsa G.P., and Liu S. Cost-effectiveness of antiplatelet agents in secondary stroke prevention: the limits of certainty. Value Health 8 5 (2005) 572-580
86. Ariesen M.J., Algra A., and Kappelle L.J. Antiplatelet drugs in the secondary prevention after stroke: differential efficacy in large versus small vessel disease? A subgroup analysis from ESPS-2. Stroke 37 1 (2006) 134-138