Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials
Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this l...
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| Veröffentlicht in: | European heart journal Jg. 43; H. 10; S. 959 |
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| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
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England
07.03.2022
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| ISSN: | 1522-9645, 1522-9645 |
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| Abstract | Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS.
We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments.
In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS.
This study is registered in PROSPERO (CRD42021258603).
A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored.
In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality.
A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome. |
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| AbstractList | Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS.
We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments.
In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS.
This study is registered in PROSPERO (CRD42021258603).
A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored.
In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality.
A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome. Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS.AIMSGuidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS.We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments.METHODS AND RESULTSWe performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments.In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS.CONCLUSIONIn patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS.This study is registered in PROSPERO (CRD42021258603).STUDY REGISTRATION NUMBERThis study is registered in PROSPERO (CRD42021258603).A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored.KEY QUESTIONA guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored.In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality.KEY FINDINGIn a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality.A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.TAKE HOME MESSAGEA guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome. |
| Author | Biondi-Zoccai, Giuseppe Pereira, Naveen L Vescovo, Giovanni Maria Capodanno, Davide Cavallari, Larisa H Gibson, Charles Michael Sibbing, Dirk Benenati, Stefano Crea, Filippo Bikdeli, Behnood Galli, Mattia Rollini, Fabiana Franchi, Francesco Ten Berg, Jurrien Mehran, Roxana Angiolillo, Dominick J |
| Author_xml | – sequence: 1 givenname: Mattia orcidid: 0000-0003-3909-182X surname: Galli fullname: Galli, Mattia organization: Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Largo Francesco Vito, 1, Rome 00168, Italy – sequence: 2 givenname: Stefano orcidid: 0000-0001-9669-4278 surname: Benenati fullname: Benenati, Stefano organization: Dipartimento di Medicina Interna e Specialità Mediche (DIMI), Policlinico San Martino IRCCS, University of Genoa, Largo Rosanna Benzi, 10, Genoa 16132, Italy – sequence: 3 givenname: Francesco surname: Franchi fullname: Franchi, Francesco organization: Division of Cardiology, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA – sequence: 4 givenname: Fabiana surname: Rollini fullname: Rollini, Fabiana organization: Division of Cardiology, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA – sequence: 5 givenname: Davide surname: Capodanno fullname: Capodanno, Davide organization: Division of Cardiology, Azienda Ospedaliero Universitaria Policlinico "G. Rodolico-San Marco", University of Catania, Via Santa Sofia, 78, Catania 95123, Italy – sequence: 6 givenname: Giuseppe surname: Biondi-Zoccai fullname: Biondi-Zoccai, Giuseppe organization: Mediterranea Cardiocentro, Via Orazio, 2, Napoli 80122, Italy – sequence: 7 givenname: Giovanni Maria surname: Vescovo fullname: Vescovo, Giovanni Maria organization: Interventional Cardiology, Department of Cardiothoracic and Vascular Science, Ospedale dell'Angelo, Via Paccagnella, 11, Venice 30174, Italy – sequence: 8 givenname: Larisa H surname: Cavallari fullname: Cavallari, Larisa H organization: Department of Pharmacotherapy & Translational Research, Center for Pharmacogenomics & Precision Medicine, University of Florida, Gainesville, FL 32611, USA – sequence: 9 givenname: Behnood surname: Bikdeli fullname: Bikdeli, Behnood organization: Clinical Trials Center, Cardiovascular Research Foundation, 1700 Broadway, New York, NY 10019, USA – sequence: 10 givenname: Jurrien surname: Ten Berg fullname: Ten Berg, Jurrien organization: Department of Cardiology and Center for Platelet Function Research, St Antonius Hospital, The Cardiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, Maastricht 6229, the Netherlands – sequence: 11 givenname: Roxana surname: Mehran fullname: Mehran, Roxana organization: Icahn School of Medicine at Mount Sinai, Cardiovascular Institute, 1 Gustave L. Levy Pl, New York, NY 10029, USA – sequence: 12 givenname: Charles Michael surname: Gibson fullname: Gibson, Charles Michael organization: Department of Medicine, Beth Israel Deaconess Medical Center, 169 Pilgrim Rd, Boston, MA 02215, USA – sequence: 13 givenname: Filippo orcidid: 0000-0002-9482-411X surname: Crea fullname: Crea, Filippo organization: Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Largo Francesco Vito, 1, Rome 00168, Italy – sequence: 14 givenname: Naveen L surname: Pereira fullname: Pereira, Naveen L organization: Department of Cardiovascular Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA – sequence: 15 givenname: Dirk orcidid: 0000-0002-0698-2696 surname: Sibbing fullname: Sibbing, Dirk organization: DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Greifswald 17475, Germany – sequence: 16 givenname: Dominick J orcidid: 0000-0001-8451-2131 surname: Angiolillo fullname: Angiolillo, Dominick J organization: Division of Cardiology, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34918066$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com. |
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| Keywords | Antiplatelet therapy Prasugrel P2Y12 inhibitors Platelet function Clopidogrel Genetic testing Acute coronary syndrome Ticagrelor |
| Language | English |
| License | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com. |
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| References | 36303423 - Eur Heart J. 2023 Jan 14;44(3):236. doi: 10.1093/eurheartj/ehac601. 35166344 - Eur Heart J. 2022 Mar 7;43(10):968-970. doi: 10.1093/eurheartj/ehac046. 36303412 - Eur Heart J. 2023 Jan 14;44(3):235. doi: 10.1093/eurheartj/ehac598. |
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| Snippet | Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS).... |
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| SubjectTerms | Acute Coronary Syndrome Humans Percutaneous Coronary Intervention Platelet Aggregation Inhibitors - adverse effects Platelet Aggregation Inhibitors - therapeutic use Prasugrel Hydrochloride - adverse effects Prasugrel Hydrochloride - therapeutic use Purinergic P2Y Receptor Antagonists - adverse effects Purinergic P2Y Receptor Antagonists - therapeutic use Randomized Controlled Trials as Topic Ticagrelor - adverse effects Ticagrelor - therapeutic use Treatment Outcome |
| Title | Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials |
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