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. 2020 Jul 14;142(2):150-160.
doi: 10.1161/CIRCULATIONAHA.120.046786. Epub 2020 May 29.

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials

Eliano P Navarese  1   2   3 , Safi U Khan  4 , Michalina Kołodziejczak  5   3 , Jacek Kubica  1   3 , Sergio Buccheri  6 , Christopher P Cannon  7 , Paul A Gurbel  8 , Stefano De Servi  9 , Andrzej Budaj  10 , Antonio Bartorelli  11 , Daniela Trabattoni  11 , E Magnus Ohman  12 , Lars Wallentin  6 , Matthew T Roe  12 , Stefan James  6
Affiliations

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials

Eliano P Navarese et al. Circulation. .

Abstract

Background: New randomized, controlled trials have become available on oral P2Y12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials.

Methods: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome.

Results: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored.

Conclusions: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.

Keywords: P2Y12 protein, human; acute coronary syndrome; meta-analysis.

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Figures

Figure 1.
Figure 1.. Meta-analyses of randomized trials for cardiovascular mortality.
A, Network meta-analysis of randomized trials for cardiovascular mortality. Pooled hazard ratios (HRs) and 95% CIs determined by network meta-analysis. B, Pairwise meta-analysis of randomized trials for cardiovascular mortality. Individual and summary hazard ratios with 95% CIs. ISAR-REACT 5 indicates Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes, PHILO indicates Phase the International Study of Ticagrelor and Clinical Outcomes in Asian ACS Patients; PLATO, PLATelet inhibition and patient Outcomes; PRASFIT-ACS, PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI; TICAKOREA, Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management; TRILOGY ACS, The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes; and TRITON–TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38.
Figure 2.
Figure 2.. Meta-analyses of randomized trials for myocardial infarction.
A, Network meta-analysis of randomized trials for myocardial infarction. Pooled hazard ratios (HRs) and 95% CIs determined by network meta-analysis. B, Pairwise meta-analysis of randomized trials for myocardial infarction. Individual and summary HRs with 95% CIs. C, Network meta-analysis of randomized trials for re–myocardial infarction. Pooled HRs and 95% CIs determined by network meta-analysis. ISAR-REACT 5 indicates Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes; PHILO, Phase the International Study of Ticagrelor and Clinical Outcomes in Asian ACS Patients; PLATO, PLATelet inhibition and patient Outcomes; PRASFIT-ACS, PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI; TICAKOREA, Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management; TRILOGY ACS, The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes; and TRITON–TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38.
Figure 3.
Figure 3.. Meta-analysis of randomized trials for definite or probable stent thrombosis.
A, Network meta-analysis of randomized trials for definite or probable stent thrombosis. Pooled hazard ratios (HRs) and 95% CIs determined by network meta-analysis. B, Pairwise meta-analysis of randomized trials for definite or probable stent thrombosis. Individual and summary HRs with 95% CIs. ISAR-REACT 5 indicates Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes; PLATO, PLATelet inhibition and patient Outcomes; PRASFIT-ACS, PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI; and TRITON–TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38.
Figure 4.
Figure 4.. Meta-analysis of randomized trials for major bleeding.
A, Network meta-analysis of randomized trials for major bleeding. Pooled hazard ratios (HRs) and 95% CIs determined by network meta-analysis. B, Pairwise meta-analysis of randomized trials for major bleeding. Individual and summary HRs with 95% CIs. ISAR-REACT 5 indicates Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes; PHILO, Phase the International Study of Ticagrelor and Clinical Outcomes in Asian ACS Patients; PLATO, PLATelet inhibition and patient Outcomes; PRASFIT-ACS, PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI; TICAKOREA, Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management; TRILOGY ACS, The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes; and TRITON–TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38.
Figure 5.
Figure 5.. Summary pooled hazard ratios (HRs) and 95% CIs determined by network meta-analysis.
The red squares indicate significant results for the investigated outcome. CV indicates cardiovascular; and MI, myocardial infarction.
See this image and copyright information in PMC

Comment in

References

    1. Tantry US, Navarese EP, Myat A, Chaudhary R, Gurbel PA. Combination oral antithrombotic therapy for the treatment of myocardial infarction: recent developments. Expert Opin Pharmacother. 2018;19:653–665. doi: 10.1080/14656566.2018.1457649 - DOI - PubMed
    1. Navarese EP, Buffon A, Kozinski M, Obonska K, Rychter M, Kunadian V, Austin D, De Servi S, Sukiennik A, Kubica J. A critical overview on ticagrelor in acute coronary syndromes. QJM. 2013;106:105–115. doi: 10.1093/qjmed/hcs187 - DOI - PubMed
    1. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, et al. ; 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;39:119–177. doi: 10.1093/eurheartj/ehx393 - DOI - PubMed
    1. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, et al. ; 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;37:267–315. doi: 10.1093/eurheartj/ehv320 - DOI - PubMed
    1. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64:e139–228. doi: 10.1016/j.jacc.2014.09.017 - DOI - PubMed

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