Efficacy and safety of alternative oral administrations of P2Y12-receptor inhibitors: Systematic review and meta-analysis

Background: Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies. Methods: Systematic research was performed on Pubmed, Cochrane Library, Biomed Central, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome). Results and discussion: Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses. These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was −59.24 PRU (95% CI from −30.61 to −87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis.