Meta-Analysis Comparing Potent Oral P2Y12 Inhibitors versus Clopidogrel in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Abstract

Background In patients with atrial fibrillation (AF) receiving percutaneous coronary intervention (PCI), current guidelines recommend against combining potent oral P2Y 12 inhibitors (i.e. ticagrelor or prasugrel) with oral anticoagulant (OAC) therapy, but the evidence is limited. Objective The aim of this meta-analysis was to compare the efficacy and safety of potent oral P2Y 12 inhibitors with clopidogrel in patients receiving OAC therapy for AF after a recent PCI. Methods Electronic databases were searched for randomized controlled trials (RCT) reporting outcomes according to the P2Y 12 inhibitor used. Major or clinically relevant non-major bleeding were the safety endpoints, while the efficacy outcomes were major adverse cardiovascular events (MACE). The potent oral P2Y 12 inhibitors prasugrel and ticagrelor were compared with clopidogrel. A subgroup analysis was conducted to evaluate the differences between patients treated with dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT). Results Four RCTs that included 10,057 patients were included in this analysis. Potent oral P2Y 12 inhibitors were associated with a significant increase in major or clinically relevant non-major bleeding compared with clopidogrel (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.06–1.59, p = 0.01; number needed to harm 18, 95% CI 12–36). This finding was consistent regardless of the concomitant antithrombotic therapy (DAT vs. TAT; p = 0.69). The risk of MACE did not differ between potent oral P2Y 12 inhibitors and clopidogrel (RR 1.02, 95% CI 0.57–1.82). Conclusions In patients receiving OAC therapy for AF after a recent PCI, potent oral P2Y 12 inhibitors increase the risk of clinically relevant bleeding compared with clopidogrel, with no evident benefit in terms of MACE reduction. Electronic supplementary material The online version of this article (10.1007/s40256-020-00436-8) contains supplementary material, which is available to authorized users.

Current views on antiplatelet therapy in acute coronary syndrome patients: the place of clopidogrel

“…Анализ в подгруппах исследования RE-DUAL PCI [36] показал, что частота больших и клинически значимых кровотечений составила 26,3% у принимавших тикагрелор и 20,1% у принимавших клопидогрел (ОШ 1,35, 95% ДИ 1,05-1,72). Метаанализ всех четырех перечисленных выше исследований [37] показал, что выбор более сильного ингибитора P2Y12 (тикагрелора или прасугрела) в сравнении с клопидогрелом ассоциируется с увеличением риска больших и клинически значимых кровотечений на треть без каких-либо преимуществ по большим ишемическим осложнениям. Крупное наблюдательное исследование TRANSLATE ACS показало, что применение прасугрела в комбинации с антикоагулянтом ассоциируется с большим риском кровотечений в сравнении с клопидогрелом как в составе тройной, так и двойной антитромботической терапии (соответственно, 39,0% vs 24,4%, p = 0,003 и 26,7% vs 19,7%, p не представлено).…”

Non–Vitamin K Antagonist Oral Anticoagulants in Coronary Artery Disease

“…49 Therefore, recent guidelines still advise against using the more potent P2Y12 inhibitors (prasugrel or ticagrelor) in AF patients post-PCI. 3,51,52 Since there are no head-to-head trials that compared NOACs directly against each other, there is no evidence to suggest one NOAC in preference to another for the management of individuals with the indication for anticoagulation after PCI. An indirect comparison of NOAC agents using a network meta-analysis also did not show superiority of one NOAC over another for AF patients post-PCI.…”

“…50 The European approach is still more cautious, recommending to terminate the triple treatment at discharge, 1 month, or 3 to 6 months depending on the individual's thrombotic and bleeding profile. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Patients with a high thrombotic risk should be treated with triple treatment for even up to 6 months, according to European guidelines. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23…”

“…3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 In general, both European and North American guidelines agree that NOAC should be preferred over VKAs in patients with AF undergoing PCI and the triple antithrombotic treatment should be as brief as feasible. 3 51 52 NOAC should be taken at the same dose as that recommended for thromboembolic protection in people with AF; lower doses are not recommended in dual-antithrombotic treatment. 50 52…”

“…3,51,52 NOAC should be taken at the same dose as that recommended for thromboembolic protection in people with AF; lower doses are not recommended in dual-antithrombotic treatment. 50,52 Ongoing Trials Several ongoing trials are awaited to fill some of the current knowledge gap. The RT-AF, APPROACH-ACS-AF, and NCT03536611 trials are studying rivaroxaban, apixaban, and dabigatran, respectively.…”