Benefits of clopidogrel in clinical practice: current data

Kochetkov A.I.; Ostroumova O.D.; Kirichenko A.A.; Aleshkovich E.V.

doi:https://doi.org/10.17116/kardio202013041322

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Abstract:

Antiplatelet therapy is one of the most important aspects in the management of patients with atherothrombotic diseases. Currently, acetylsalicylic acid and P2Y₁₂ receptor blockers (clopidogrel, ticagrelor and prasugrel) are used as antiplatelet drugs. Recently, the results of several studies and meta-analyses have been published. According to these data, clopidogrel is characterized by comparable efficacy and better safety profile compared to other P2Y₁₂ blockers. In addition, de-escalation algorithms for antiplatelet therapy with rejection of ticagrelor/prasugrel in favor of clopidogrel are actively studied. The available data similarly indicate that this approach ensures adequate prevention of ischemic complications and reduces the risk of bleeding. Thus, more favorable general prognostic effect is expected. An important advantage of clopidogrel is long-standing experience of clinical application and an extensive evidence base confirming effectiveness and safety of this drug. As a result, clopidogrel is included into the leading international guidelines. These documents emphasize that clopidogrel is a first-line antiplatelet drug for dual and triple antithrombotic therapy in patients with atrial fibrillation and previous thrombolysis. In addition, clopidogrel is effective for symptomatic atherosclerosis of the carotid and lower limb arteries, especially in patients after previous stenting of these vessels.

Keywords:

antiplatelet therapy

guidelines

clopidogrel

coronary artery disease

effectiveness

safety

Authors:

Kochetkov A.I.

Russian Medical Academy of Continuous Professional Education

Ostroumova O.D.

Russian Medical Academy of Continuous Professional Education

SPIN RSCI: 3910-6585
Scopus AuthorID: 7004067629
ResearcherID: M-9553-2014
ORCID: 0000-0002-0795-8225

Kirichenko A.A.

Russian Medical Academy of Continuous Professional Education

Aleshkovich E.V.

Botkin Municipal Clinical Hospital

Received:

19.05.2020

Accepted:

12.06.2020

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References:

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. https://doi.org/10.1093/eurheartj/ehx393
Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. https://doi.org/10.1093/eurheartj/ehz425
Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763-816. https://doi.org/10.1093/eurheartj/ehx095
Kandaswamy E., Zuo L. Recent Advances in Treatment of Coronary Artery Disease: Role of Science and Technology. Int J Mol Sci. 2018;19(2). pii: E424. https://doi.org/10.3390/ijms19020424
Smertnost’ ot boleznej serdtsa i sosudov dostigla minimuma c 2010 goda. (In Russ.) Accessed May 18, 2020. https://iz.ru/722507/elina-khetagurova/smertnost-ot-boleznei-serdtca-i-sosudov-dostigla-minimuma-c-2010-goda
Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30-47. https://doi.org/10.1038/nrcardio.2014.156
Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39(3):213-260. https://doi.org/10.1093/eurheartj/ehx419
Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Jüni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165. https://doi.org/10.1093/eurheartj/ehy394
Koski R, Kennedy B. Comparative Review of Oral P2Y12 Inhibitors. P T. 2018;43(6):352-357.
Ostroumova OD, Kochetkov AI, Pereverzev AP, Kravchenko EV, Kazyulin AN, Andreev DN, Pavleeva EE. The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications. Therapeutic Archive. 2019;91(8):118-126. (In Russ.)
Kochetkov AI, Ostroumova OD, Kravchenko EV, Bondaretc OV, Guseva TF. Combined therapy with proton pump inhibitors and clopidogrel — focus on cardiovascular risk. Consilium Medicum. 2019;21(1):56-66. (In Russ.) https://doi.org/10.26442/20751753.2019.1.190194
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494-502. https://doi.org/10.1056/NEJMoa010746
Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, McCabe CH, Braunwald E; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352(12):1179-1189. https://doi.org/10.1056/NEJMoa050522
Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ; CREDO Investigators. Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19):2411-2420. https://doi.org/10.1001/jama.288.19.2411
Ringleb PA, Bhatt DL, Hirsch AT, Topol EJ, Hacke W; Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events Investigators. Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. Stroke. 2004;35(2):528-532. https://doi.org/10.1161/01.STR.0000110221.54366.49
Sacco RL, Diener HC, Yusuf S, Cotton D, Ounpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen ST, Cunha L, Dahlöf B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW; PRoFESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359(12):1238-1251. https://doi.org/10.1056/NEJMoa0805002
Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706-1717. https://doi.org/10.1056/NEJMoa060989
Bhatt DL, Flather MD, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Fabry-Ribaudo L, Hu T, Topol EJ, Fox KA; CHARISMA Investigators. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49(19):1982-1988. https://doi.org/10.1016/j.jacc.2007.03.025
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-2015. https://doi.org/10.1056/NEJMoa0706482
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; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. https://doi.org/10.1056/NEJMoa0904327
Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315. https://doi.org/10.1093/eurheartj/ehv320
Monti S, Grosso V, Todoerti M, Caporali R. Randomized controlled trials and real-world data: differences and similarities to untangle literature data. Rheumatology (Oxford). 2018;57(57 Suppl 7):vii54-vii58. https://doi.org/10.1093/rheumatology/key109
Saturni S, Bellini F, Braido F, Paggiaro P, Sanduzzi A, Scichilone N, Santus PA, Morandi L, Papi A. Randomized Controlled Trials and real life studies. Approaches and methodologies: a clinical point of view. Pulm Pharmacol Ther. 2014;27(2):129-138. https://doi.org/10.1016/j.pupt.2014.01.005
Turgeon RD, Koshman SL, Youngson E, Har B, Wilton SB, James MT, Graham MM. Association of Ticagrelor vs Clopidogrel With Major Adverse Coronary Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA Intern Med. 2020;180(3):420-428. https://doi.org/10.1001/jamainternmed.2019.6447
Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG, Cornel JH, Bhatt DL, Clemmensen P, Martinez F, Ardissino D, Nicolau JC, Boden WE, Gurbel PA, Ruzyllo W, Dalby AJ, McGuire DK, Leiva-Pons JL, Parkhomenko A, Gottlieb S, Topacio GO, Hamm C, Pavlides G, Goudev AR, Oto A, Tseng CD, Merkely B, Gasparovic V, Corbalan R, Cinteză M, McLendon RC, Winters KJ, Brown EB, Lokhnygina Y, Aylward PE, Huber K, Hochman JS, Ohman EM; TRILOGY ACS Investigators. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367(14):1297-1309. https://doi.org/10.1056/NEJMoa1205512
Guan W, Lu H, Yang K. Choosing between ticagrelor and clopidogrel following percutaneous coronary intervention: A systematic review and Meta-Analysis (2007-2017). Medicine (Baltimore). 2018;97(43):e12978. https://doi.org/10.1097/MD.0000000000012978
Wang D, Yang XH, Zhang JD, Li RB, Jia M, Cui XR. Compared efficacy of clopidogrel and ticagrelor in treating acute coronary syndrome: a meta-analysis. BMC Cardiovasc Disord. 2018 Nov 29;18(1):217. https://doi.org/10.1186/s12872-018-0948-4
Doll JA, Neely ML, Roe MT, Armstrong PW, White HD, Prabhakaran D, Winters KJ, Duvvuru S, Sundseth SS, Jakubowski JA, Gurbel PA, Bhatt DL, Ohman EM, Fox KA; TRILOGY ACS Investigators. Impact of CYP2C19 Metabolizer Status on Patients With ACS Treated With Prasugrel Versus Clopidogrel. J Am Coll Cardiol. 2016;67(8):936-947. https://doi.org/10.1016/j.jacc.2015.12.036
Angiolillo DJ, Patti G, Chan KT, Han Y, Huang WC, Yakovlev A, Paek D, Del Aguila M, Girotra S, Sibbing D. De-escalation from ticagrelor to clopidogrel in acute coronary syndrome patients: a systematic review and meta-analysis. J Thromb Thrombolysis. 2019;48(1):1-10. https://doi.org/10.1007/s11239-019-01860-7
Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komócsi A, Dézsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017;390(10104):1747-1757. https://doi.org/10.1016/S0140-6736(17)32155-4
Cuisset T, Deharo P, Quilici J, Johnson TW, Deffarges S, Bassez C, Bonnet G, Fourcade L, Mouret JP, Lambert M, Verdier V, Morange PE, Alessi MC, Bonnet JL. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J. 2017;38(41):3070-3078. https://doi.org/10.1093/eurheartj/ehx175
Ostroumova OD, Kochetkov AI, Chernyaeva MS. Arterial Hypertension in Older Adults in the Light of New European Guidelines 2018. Rational Pharmacotherapy in Cardiology. 2018;14(5):774-784. (In Russ.) https://doi.org/10.20996/1819-6446-2018-14-5-774-784
Oganov RG, Simanenkov VI, Bakulin IG, Bakulina NV, Barbarash OL, Boytsov SA, Boldueva SA, Garganeeva NP, Doshchitsin VL, Karateev AE, Kotovskaya YV, Lila AM, Lukyanov MM, Morozova TE, Pereverzev AP, Petrova MM, Pozdnyakov YM, Syrov AV, Tarasov AV, Tkacheva ON, Shalnova SA. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Cardiovascular Therapy and Prevention. 2019;18(1):5-66. (In Russ.) https://doi.org/10.15829/1728-8800-2019-1-5-66
Bavry AA. Randomized Comparison of Clopidogrel Versus Ticagrelor or Prasugrel in Patients of 70 years or Older With Non-ST-Elevation Acute Coronary Syndrome — POPular AGE. Link available on 18.05.2020. https://www.acc.org/latest-in-cardiology/clinical-trials/2019/08/30/09/59/popular-age
Orange Book Preface. Link available on 18.05.20. https://www.fda.gov/drugs/development-approval-process-drugs/orange-book-preface
Leslie KH, McCowan C, Pell JP. Adherence to cardiovascular medication: a review of systematic reviews. J Public Health (Oxf). 2019;41(1):e84-e94. https://doi.org/10.1093/pubmed/fdy088