Secondary prevention in minor ischemic stroke with antiplatelet treatment. Systematic review and meta-analysis of comparative studies with aspirin under non-inferiority criteria. / Prevención secundaria en el ictus isquémico menor con el tratamiento antiplaquetario. Revisión sistemática y metanálisis de estudios comparativos con aspirina bajo criterios de no inferioridad.

  • Gilberto Vizcaíno Universidad Técnica de Manabí
  • Juan Paul Montalvo Herdoiza Universidad Técnica de Manabí
  • Aline Siteneski Universidad Técnica de Manabí
  • Wendy Tauriz Navarro Universidad Técnica de Manabí
Palabras clave: secondary prevention, ischemic stroke, antiplatelet treatment, meta-analysis, non-inferiority, prevención secundaria, accidente cerebrovascular isquémico, tratamiento antiplaquetario, metanálisis, no inferioridad.

Resumen

Abstract.

Minor ischemic stroke is the most frequent presentation of cerebral vascular disease and treatment with antiplatelet drugs can be used for the prevention of its recurrence. This systematic review and meta-analysis was aimed to assess non-inferiority criteria about the effect in the comparison of different antiplatelet schemes using aspirin as active control. Twelve randomized studies with a total of 52204 patients were chosen. All met the inclusion criteria with minor recurrent ischemic stroke as end point and any extracranial bleeding as safety event. The results showed a significant risk reduction of 22% [RR (95% CI) = 0.78 (0.72-0.84), p<0.0001, NNT: 67] in the recurrence of ischemic events with any antiplatelet drug (combined or not with aspirin) versus aspirin alone and there were no differences in the bleeding risk [RR (95% CI) = 1.02 (0.74- 1.41), p= 0.899, NNH: 500]. Dual antiplatelet therapy (DAPT) and cilostazol were more effective compared with aspirin alone (22% and 32% risk reduction respectively) but only cilostazol showed a higher reduction (52%) of bleeding events. In conclusion, although in some instances equivalence was demonstrated, a clinical superiority in the risk reduction for recurrent ischemic stroke of any antiplatelet treatment versus aspirin alone was observed. With the sole exception of the cilostazol trials there was an increase of the bleeding risk when the antiplatelet drugs treatments were compared with aspirin alone.

Resumen.

El accidente cerebrovascular (ictus) isquémico menor es la presentación más frecuente de enfermedad vascular cerebral y se puede utilizar el tratamiento con fármacos antiplaquetarios para la prevención de su recurrencia. Esta revisión sistemática y metanálisis tuvo como objetivo evaluar los criterios de no inferioridad sobre el efecto en la comparación de diferentes esquemas antiplaquetarios que usan aspirina como control activo. Se eligieron doce estudios aleatorios con un total de 52.204 pacientes. Todos cumplieron los criterios de inclusión para ictus isquémico recurrente menor como desenlace primario y hemorragia extracraneal como evento de seguridad. Los resultados mostraron una reducción significativa del riesgo del 22% [RR (IC 95%) = 0,78 (0,72-0,84), p <0,0001, NNT: 67] en la recurrencia de eventos isquémicos con cualquier fármaco antiplaquetario (combinado o no con aspirina) versus aspirina sola y no hubo diferencias en el riesgo de hemorragia [RR (IC 95%) = 1.02 (0.74-1.41), p = 0.899, NNH: 500]. La terapia antiplaquetaria dual (DAPT) y el cilostazol fueron más efectivos en comparación con la aspirina sola (22% y 32% de reducción de riesgo respectivamente) pero solo el cilostazol mostró una mayor reducción (52%) de los eventos hemorrágicos. En conclusión, aunque en algunos casos se demostró la equivalencia, se observó una superioridad clínica en la reducción del riesgo de accidente cerebrovascular isquémico recurrente de cualquier tratamiento antiplaquetario versus aspirina sola. Con la única excepción de los ensayos con cilostazol, hubo un aumento del riesgo de hemorragia cuando los tratamientos con fármacos antiplaquetarios se compararon con la aspirina sola.

Citas

Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJ, Demaerschalk BM, American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947. DOI: 10.1161/ STR.0b013e318284056a.

Zerna C, Thomalla G, Campbell B C V, Rha JH, Hill MD. Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke. Lancet 2018;392:1247–1256. DOI: 10.1016/ s0140-6736(18)31874-9.

Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and its use in future stroke trials. Stroke 2017;48:2007-2012. DOI: 10.1161/STROKEAHA.117.017866.

Dufouil C, Beiser A, McLure LA, Wolf PA, Tzourio C, Howard VJ, Westwood AJ, Himali JJ, Sullivan L, Aparicio HJ, Kelly- Hayes M, Ritchie K, Kase CS, Pikula A, Romero JR, D’Agostino RB, Samieri C, Vasan RS, Chêne G, Howard G, Seshadri S. Revised Framingham Stroke Risk Profile to reflect temporal trends. Circulation. 2017;135(12):1145-1159.

Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K. on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the rarly management of patients with aute ischemic stroke. Stroke 2018;49:e46–e99. DOI: 10.1161/STR.0000000000000158.

Prasad K, Siemieniuk R, Hao Q, Guyatt G, O’Donnell M, Lytvyn L, Heen AF, Agoritsas T, Vandvik PO, Gorthi SP, Fisch L, Jusufovic M, Muller J, Booth B, Horton E, Fraiz A, Siemieniuk J, Fobuzi AC, Katragunta N, Rochwerg B. Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline. BMJ 2018;363: k5130. DOI:10.1136/bmj.k5130.

Mayer L, Ferrari J, Krebs S, Boehme C, Toell T, Matosevic B, Tinchon A, Brainin M, Gattringer T, Sommer P, Thun P, Wil- leit J, Lang W, Kiechl S, Knoflach M, Austrian Stroke Unit Collaborators. ABCD3- I Score and the risk of early or 3-month stroke recurrence in tissue- and time-based definitions of TIA and minor sroke. J Neurol 2018;265 (3):530-534. DOI: 10.1007/ s00415-017-8720-8.

Odier C, Michel P. Common stroke syndromes. Textbook of stroke medicine. Brainin M, Heiss WD eds. Cambridge University Press 2019, pp: 169-181. DOI: 10. 1017/9781108659574.

Kapil N, Datta YH, Alakbarova N, Bershad E, Selim M, Liebeskind DS, Divani AA. Antiplatelet and anticoagulant therapies for prevention of ischemic stroke. Clin Appl Thromb Hemost 2016;23(4):301–318. DOI: 10.1177/1076029616660762.

The International Stroke Trial (IST): A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke: International Stroke Trial Collaborative Group. Lancet 1997;349:1569–1581.

Chinese Acute Stroke Trial, CAST Collaborative Group. Randomised placebo-con- trolled trial of early aspirin use in 20,000 patients with acute ischaemic stroke: Lancet 1997;349:1641–1649.

Sandercock PA, Counsell C, Tseng MC, Cecconi E. Oral antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev. 2014: Https://doi. org/10.1002/14651858.CD000029.

Campuzano Maya G. Inhibidores del receptor plaquetario P2Y12. Parte 1 de 2: escenario de acción, farmacología, aplicación clínica y limitaciones de su uso. Med Lab 2017;23:13-44.

Gresele P, Momi S, Falcinelli E. Antipla- telet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 2011;72:634–646.

Yamamoto H, Takahashi K, Watanabe H, Yoshikawa Y, Shirakawa R, Higashi T, Kawato M, Ikeda T, Tabuchi A, Morimoto T, Kita T, Horiuchi H. Evaluation of the antiplatelet effects of cilostazol, a phos- phodiesterase 3 inhibitor, by VASP phos- phorylation and platelet aggregation. Circ J 2008;72:1844–1851.

Siebler M, Hennerici MG, Schneider D, von Reutern GM, Seitz RJ, Röther J, Witte OW, Hamann G, Junghans U, Villringer A, Fiebach JB. Safety of tirofiban in acute ischemic stroke: the SaTIS trial. Stroke 2011;42:2388–2392. DOI: 10.1161/STRO KEAHA.110.599662.

Pancioli AM, Broderick J, Brott T, Tom- sick T, Khoury J, Bean J, del Zoppo G, Kleindorfer D, Woo D, Khatri P, Castaldo J, Frey J, Gebel J Jr, Kasner S, Kidwell C, Kwiatkowski T, Libman R, Mackenzie R, Scott P, Starkman S, Thurman RJ; for the CLEAR Trial Investigators. The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial. Stroke 2008;39:3268–3276. DOI: 10.1161/STROKEAHA.108.517656.

Adeoye O, Sucharew H, Khoury J, Tom- sick T, Khatri P, Palesch Y, Schmit PA, Pancioli AM, Broderick JP; for the CLEAR-ER, IMS III, and ALIAS Part 2 Investigators. Recombinant tissue-type plas- minogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alonein acute ischemic stroke: propensity score-matched post hoc analysis. Stroke 2015;46:461–464. DOI: 10.1161/ STROKEAHA.114.006743.

Adeoye O, Sucharew H, Khoury J, Vagal A, Schmit PA, Ewing I, Levine SR, Demel S, Eckerle B, Katz B, Kleindorfer D, Stettler B, Woo D, Khatri P, Broderick JP, Pancioli AM. Combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator in acute ischemic stroke-full dose regimen stroke trial. Stroke 2015;46:2529–2533. DOI: 10.1161/STRO KEAHA.115.010260.

Ciccone A, Motto C, Abraha I, Cozzolino F, Santilli I. Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke. Cochrane Data base Syst Rev 2014:CD005208.

Adams HP Jr, Effron MB, Torner J, Dávalos A, Frayne J, Teal P, Leclerc J, Oemar B, Padgett L, Barnathan ES, Hacke W; for the AbESTT-II Investigators. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke 2008;39:87–99. DOI: 10.1161/STROKEAHA.106.476648.

Bath PM, Woodhouse LJ, Appleton JP, Beridze M, Christensen H, Dineen RA, Flaherty K, Duley L, England TJ, Havard D, Heptinstall S, James M, Kasonde C, Krishnan K, Markus HS, Montgomery AA, Pocock S, Randall M, Ranta A, Robinson TG, Scutt P, Venables GS, Sprigg N. Triple ver- sus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT. Health Technol Assess 2018;22(48):1-76. DOI: 10.3310/hta22480.

Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: ¿is blinding necessary? Control Clin Trials1996;17:1–12.

Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. DOI: 10.1136/bmj.d5928.

GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarc- tion. N Engl J Med 1993;329:67382.

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057.

Bhatt DL, Fox KAA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, for the CHARISMA Investiga- tors. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706- 1717. DOI: 10.1056/NEJMoa060989.

The SPS3 Investigators. Effects of Clopido- grel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012;367: 817-825. DOI: 10.1056/NEJMoa1204133.

Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC, for the CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013; 369:11-19. DOI: 10.1056/NEJMoa1215340.

Côté R, Zhang Y, Hart RG, McClure LA, Anderson DC, Talbert RL, Benavente OR. ASA failure. Does the combination ASA/ clopidogrel confer better long-term vascular protection? Neurology 2014;82:382– 389.

Hong KS, Lee SH, Kim EG, Cho KH, Chang DI, Rha JH, Bae HJ, Lee KB, Kim DE, Park JM, Kim HY, Cha JK, Yu KH, Lee YS, Lee SJ, Choi JC, Cho YJ, Kwon SU, Kim GM, Sohn SI, Park KY, Kang DW, Sohn CH, Lee J, Yoon BW; COMPRESS Investigators. Recurrent ischemic lesions after acute atherothrombotic stroke clopidogrel plus aspirin versus aspirin alone. Stroke 2016;47:2323-2330. DOI: 10.1161/ STROKEAHA.115.01229.

Johnston SC, Easton D, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY, The POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018; 379(3): 215–225. DOI: 10.1056/ NEJMoa1800410.

Huang Y, Cheng Y, Wu J, Li Y, Xu E, Hong Z, Li Z, Zhang W, Ding M, Gao X, Fan D, Zeng J, Wong K, Lu C, Xiao J, Yao C, on behalf of the cilostazol versus aspirin for secondary Ischaemic stroke prevention (CASISP) cooperation investigators. Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. Lancet Neurol 2008;7:494–499. DOI: 10.1016/S1474-4422(08)70094-2.

Shinohara Y, Katayama Y, Uchiyama S, Yamaguchi T, Handa S, Matsuoka K, Ohashi Y, Tanahashi N, Yamamoto H, Genka C, Kitagawa Y, Kusuoka H, Nishimaru K, Tsushima M, Koretsune Y, Sawada T, Hamada C, for the CSPS 2 group. Cilostazol for prevention of secondary stroke (CSPS-2): an aspirin-controlled, double-blind, ran- domized non-inferiority trial. Lancet Neurol 2010;9:959–968 DOI: 10.1016/S14 74-4422(10)70198-8.

Kim BJ, Lee EJ, Kwon SU, Park JH, Kim YJ, Hong KS, Wong LKS, Yu S, Hwang YH, Lee JS, Lee J, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Navarro JC, Kang DW; PICASSO investigators. Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet Neurol 2018;17:509–518. DOI: 10.1016/S1474-4422(18)30128-5.

Toyoda K, Uchiyama S, Yamaguchi T, Easton JD, Kimura K, Hoshino H, Sakai N, Okada Y, Tanaka K, Origasa H0, Naritomi H, Houkin K, Yamaguchi K, Isobe M, Minematsu K; CSPS.com Trial Investigators. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicenter, open-label, randomized controlled trial. Lancet Neurol 2019;18(6):539-548. DOI: 10.1016/S1474-4422(19)30148-6.

Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KSL, for the SOCRATES Steering Committee and Investigator. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 2016;375:35-43. DOI: 10.1056/NEJ- Moa1603060.

The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ES- PRIT): randomized controlled trial. Lancet 2006;367(9523):1665–1673. DOI: 10. 1016/s0140-6736(06)68734-5.

Ferreira-González I. Bases para la inter- pretación de los estudios de no inferioridad: a propósito de los estudios ROCKET– AF, RE-LY y ARISTOTLE. Rev Esp Cardiol 2014;67(6):432–435.

Vizcaíno G. La Estadística al alcance del Médico. Análisis crítico de ensayos clínicos. Capítulo III. Los estudios de no inferioridad en clínica médica. Ediciones Astro Data, ISBN 978-980-402-254-5, Maracaibo, pp 153.

Hung HM, Wang SJ, Tsong Y, Lawrence J, O’neil RT. Some fundamental issues with non-inferiority testing in active controlled trials. Stat Med 2003;22:213-225.

Pluchino S. Estudios clínicos de no inferioridad y de equivalencia: metodología, análisis e interpretación de los resultados. Avances Cardiol 2009; 29:76-81.

Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJW, CONSORT Group. Reporting of noninferiority and equivalence randomized trials. An extension of the CONSORT Statement. JAMA 2006; 295(10):1152-1160. DOI: 10.1001/jama.295.10.1152.

Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarc- tion, and stroke in high risk patients. BMJ 2002;324(7329):71-86.

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med 2009;6(7): e1000097. DOI: 10.1371/journal.pmed.1000097.

Higgins JPT, Thompson SG, Deeks JJ, Alt- man DG. Measuring inconsistency in meta- analyses. BMJ 2003;327:557-560.

Rothwell PM, Algra A, Chen Z, Diener HC, Norrving B, Mehta Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke:time-course analysis of randomised trials. Lancet 2016; 388: 365–375. DOI: 10.1016/S0140-6736(16)30468-8.

Squizzato A, Bellesini M, Takeda A, Mid- deldorp S, Donadini MP. Clopidogrel plus aspirin versus aspirin alone for prevent- ing cardiovascular events. Cochrane Daminor ischaemic stroke or high risk tran- sient ischaemic attack: systematic review and meta-analysis. BMJ 2018; 363:k5108 DOI: https://doi.org/10.1136/bmj.k5108.

Sudlow CL, Mason G, Maurice JB, Wed- derburn CJ, Hankey GJ. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database of Systematic Reviews 2009. DOI: 10.1002/14651858.cd001246.

Kwok CS, Shoamanesh A, Copley HC, Myint PK, Loke YK, Benavente OR. Ef- ficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke 2015;46:1014–1023.

Han SW, Lee SS, Kim SH, Lee JH, Kim GS, Kim O-J, Koh L-S, Lee JY, Suk S-H, Lee SI, Nam HS, Kim W-J, Yong SW, Lee K-Y, Park JH. Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo controlled trial. Eur Neurol 2013;69:33–40.

Yi X, Zhou Q, Lin J, Chi L. Aspirin resistance in Chinese stroke patients increased the rate of recurrent stroke and other vascular events. Int J Stroke 2013;8(7):535-539. DOI: 10.1111/j.1747-4949.2012.00929.

Depta JP, Fowler J, Novak E, Katzan I, Bakdash S, Kottke-Marchant K, Bhatt DL. Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack. Stroke 2012;43 (9):2376-2381.

Campuzano Maya G. Resistencia a la aspirina: un problema latente de alto riesgo. Med Lab 2016;22:13-54.

Campuzano Maya G. Inhibidores del retabase of Systematic Reviews 2017. DOI:10.1002/14651858.cd005158.

Palacio S, Hart RG, Pearce LA, Anderson DC, Sharma M, Birnbaum LA, and Benavente OR. Effect of addition of clopidogrel to aspirin on stroke incidence: Meta-analysis of randomized trials. Int J Stroke 2015;10(5):686–691. DOI: 10.1111/ijs. 12050.

Hao Q, Tampi M, O’Donnell M, Foroutan P, Siemieniuk RAC, Guyatt G. Clopidogrel plus aspirin versus aspirin alone for acuteología, Diagnóstico y manejo de la resistencia. Med Lab 2017;23:113-148.

Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Antiplatelet regimen for patients with breakthrough strokes while on aspirin: a systematic review and meta- analysis. Stroke 2017;48 (9):2610-2613.

Chin CT, Neely B, Ohman M, Armstrong PW, Corbalán R, White HD, Prabhakaran D, J. Winters KJ, Fox KAA Roe MT, for the

TRILOGY ACS Investigators. Time-varying effects of prasugrel versus clopidogrel on the long-term risks of stroke after acute coronary syndromes. Results from the TRILOGY ACS Trial. Stroke 2016;47:1135-1139. DOI: 10.1161/STROKEAHA.115.012454.

Wang Y, Pan Y, Zhao X, Li H, Wang D, Johnston SC, Liu L, Meng X, Wang A, Wang C, Wang Y. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack (CHANCE) Trial one-year outcomes on be- half of the CHANCE Investigators. Circulation 2015;132:40-46. DOI: 10.1161/CIR- CULATIONAHA.114.014791).

Pan Y, Jing J, Chen W, Meng X, Li H, Zhao X, CHANCE investigators. Risks and benefits of clopidogrel–aspirin in minor stroke or TIA Time course analysis of CHANCE. Neurology 2017;88:1906–1911.

Del Brutto VJ, Chaturvedi S, Diener HS, Romano JG, Sacco RL. Antithrombotic therapy to prevent recurrent strokes in ischemic cerebrovascular disease. J Am Coll Cardiol 2019;74:786–803.

Kheiri B, Osman M, Abdalla A, Haykal T, Swaid B, Ahmed S, Chahine A, Hassan M, Bachuwa G, Al Qasmi M, Bhatt DL. Clopi- dogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of ran- domized clinical trials. J Thromb Thrombolysis 2019;47(2):233-247. DOI: 10.1007/ s11239-018-1786-z.

Ye MB, Chen YL, Wang Q, An J, Ye F, Jing P. Aspirin plus clopidogrel versus aspirin mono- therapy for ischemic stroke: a meta-analysis. Scand Cardiovasc J 2019;53(4):169-175. DOI:10.1080/14017431.2019.1620962.

Geeganage CM, Diener HC, Algra A, Chen C, Topol EJ, Dengler R, Markus HS, Bath MW, Bath PM. Acute antiplatelet stroke trialists collaboration. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke 2012;43(4):1058-1066. DOI: 10.1161/ STROKEAHA.111.637686.

Gouya G, Arrich J, Wolzt M, Huber K, Verheugt FW, Gurbel PA, Pirker-Kees A, Siller-Matula JM. Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. Stroke 2014;45(2):492-503. DOI: 10.1161/STRO KEAHA.113.002590.

Publicado
2021-01-13
Cómo citar
Vizcaíno, G., Montalvo Herdoiza, J. P., Siteneski, A., & Tauriz Navarro, W. (2021). Secondary prevention in minor ischemic stroke with antiplatelet treatment. Systematic review and meta-analysis of comparative studies with aspirin under non-inferiority criteria. / Prevención secundaria en el ictus isquémico menor con el tratamiento antiplaquetario. Revisión sistemática y metanálisis de estudios comparativos con aspirina bajo criterios de no inferioridad. Investigación Clínica, 61(3), 265-282. https://doi.org/10.22209/IC.v61n3a06