Efficacy and safety of newer P2Y12 inhibitors for acute coronary syndrome: a network meta-analysis

Abstract

Whether newer P2Y12 inhibitors are more efficacious and safer than clopidogrel and whether there is a superior one remain uncertain. We compared the effect of P2Y12 inhibitors on clinical outcomes in patients with acute coronary syndrome (ACS). Randomized controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin were searched. Sixteen trials with altogether 77,896 patients were included. Compared to clopidogrel, cardiovascular mortality was reduced with prasugrel (OR 0.85, 95% CI 0.75–0.97) and ticagrelor (0.82, 0.73–0.93). Myocardial infarction (0.75, 0.63–0.89) and major adverse cardiovascular events (0.80, 0.69–0.94) were reduced by prasugrel. Stent thrombosis was reduced by prasugrel (0.49, 0.38–0.63), ticagrelor (0.72, 0.57–0.90), and cangrelor (0.59, 0.43–0.81). It was reduced more by prasugrel than ticagrelor (0.69, 0.51–0.93). There were more major bleeds with prasugrel (1.24, 1.05–1.48). Thrombolysis in Myocardial Infarction (TIMI) major bleeding was increased with prasugrel compared to clopidogrel (1.36, 1.11–1.66) and ticagrelor (1.33, 1.06–1.67). TIMI minor bleeding was increased with prasugrel (1.44, 1.16–1.77) and cangrelor (1.47, 1.01–2.16) compared to clopidogrel while it was increased with prasugrel compared to ticagrelor (1.32, 1.01–1.72). Prasugrel is preferable to those ACS patients at low bleeding risk to reduce cardiovascular events whereas ticagrelor is a relatively safe antiplatelet drug of choice for most patients.

Early vs. Delayed Initiation of Treatment With P2Y12 Inhibitors in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

“…This meta-analysis of randomized trials comparing different initiations of P2Y 12 inhibitors increases our understanding of the strengths and weaknesses of the available evidence regarding the best timing to start DAP and pinpoints the need for more studies to properly define the optimal time of initiation of each P2Y 12 inhibitor in patients with NSTE-ACS. Compared with previous meta-analyses ( 13 , 24 , 27 , 29 ) our study presents a number of differences and advantages: i) it is the first meta-analysis focused on the timing of administration rather than on the comparison between drugs, ii) it is restricted to the initiation of P2Y 12 inhibitors in patients with NSTE-ACS, probably the most controversial scenario for clinical decision-making ( 4 , 5 , 24 , 34 ), iii) it summarizes all available information, including direct evidence and indirect estimations, providing a quantitative proxy of the potential benefits and risks of each therapeutic strategy with each P2Y 12 inhibitor compared with the other options; iv) in contrast to the meta-analysis by Navarese et al ( 23 ), it includes open label RCTs, as it is very difficult to have (and unlikely to happen) double blind face-to-face comparisons between all the P2Y 12 inhibitors and time strategies; v) it is the only review that includes information on the delayed treatment with ticagrelor; vi) it includes patients of all ages, not only the elderly ( 24 ), and vii) it includes an analysis of cardiovascular mortality, a relevant endpoint not available in all the studies ( 24 , 27 ). However, this review should be interpreted with caution considering a number of limitations.…”

“…We have incorporated all trials including different times of P2Y 12 initiation by any design. Compared with clopidogrel, prasugrel reduces ischemic events, such as MACE, stent thrombosis ( 27 , 28 ), cardiovascular mortality, and stroke ( 29 ). However, the timing of administration makes an important difference.…”

Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials

“…41 Heterogeneity was defined as the variability of results across trials, with τ 2 <0.04 indicating a low level and τ 2 >0.4 a high level. [42][43][44] The fit of the model to the data was measured by calculating the posterior mean residual deviance. 38 If the mean of the residual deviance is similar to the number of data points of the model, it indicates that the model fits the data adequately.…”

Clinical efficacy and safety of tirofiban combined with conventional dual antiplatelet therapy in ACS patients undergoing PCI

“…As an important supplement to oral medicine, intravenous aggrastat has been proven to provide a more rapid and sustained inhibition of platelet function and bridge the initial treatment gap 33 , 34 . Clopidogrel, with a less efficacy than new P2Y12 receptor inhibitor 35 , requires the addition of GPI when the blood concentration does not reach the standard level to avoid the formation of stent thrombosis. A recent large retrospective study suggests that a short regimen of GPI is protective against stent thrombosis risk in morphine-treated STEMI patients, who are potentially exposed to increased risk of acute stent thrombosis due to delayed absorption of oral P2Y 12 inhibitors 36 .…”