engleski

The effect of P2Y12 inhibitor pretreatment vs. no pretreatment on major bleeding among patients with NSTE-ACS: an updated meta-analysis and meta- regression pooling 41,548 patients from 11 studies

Background: Recent European Society of Cardiology (ESC) guidelines for the management of non-ST elevation acute coronary syndromes (NSTE-ACS) do not recommend routine pretreatment with P2Y12 inhibitors in patients in whom coronary anatomy is not known and an early invasive management is planned. Purpose: To investigate the impact of P2Y12 pretreatment vs. no pretreatment on short-term major bleeding events among patients with NSTE- ACS. Methods: MEDLINE and EMBASE databases were systematically searched to find interventional or observational studies that investigated the use of P2Y12 inhibitors as a pretreatment vs. no pretreatment in NSTE-ACS population. Studies that reported major bleeding events, as adjudicated by study' investigators, during hospitalization or within 30 days since randomization were included. Random-effects meta-analysis was performed with prespecified subgroup analysis concerning more potent P2Y12 inhibitor use and drug-eluting stent (DES) uptake >50%. For the primary analysis, the odds ratio (OR) with 95% confidence intervals (95% CI) were reported. Heterogeneity across studies was inspected by I2 statistic. Meta-regression was performed to assess potential interaction of variables including percutaneous coronary intervention (PCI) receipt, NSTE-ACS subtype, DES uptake >50%, and potent P2Y12 inhibitor use with the primary outcome. Results: Eleven studies that provided data on major bleeding were included (6 randomized clinical trials, 4 registry-based studies, and 1 prespecified analysis of an RCT) accumulating a total of 41, 548 patients with pooled 1366 major bleeding events (871 in the pretreatment and 495 in the no-pretreatment group). Most of the studies were older than 10 years and used clopidogrel as a pretreatment while the average rate of PCI receipt was 78.2%. Low-to-moderate heterogeneity was detected across studies. Pretreatment with P2Y12 inhibitors increased the likelihood of major bleeding (OR 1.245, 95% CI 1.092–1.419) across all studies analyzed while in contemporary NSTE-ACS cohorts with high penetration of DES platforms and agents more potent than clopidogrel, this effect was borderline (OR 1.241, 95% CI 0.901–1.709 – Figure 1 and OR 1.443, 95% CI 0.742–2.807 – Figure 2, respectively). Of all variables, the use of potent P2Y12 inhibitors was independently associated with the increase of major bleeding events (coefficient 0.743, 95% CI 0.133–1.354, P=0.017). Conclusions: Our updated results show that P2Y12 pretreatment was associated with the increased likelihood of major bleeding with this effect diminished in contemporary NSTE-ACS cohorts, although the latter could be attributed to presence of heterogeneity. The use of potent P2Y12 agents was a significant modifier of major bleeding. Taken together, routine pretreatment with P2Y12 inhibitors in NSTE-ACS increases the likelihood of major bleeding with this effect generally being enhanced by potent antiaggregation used, regardless of pretreatment utilization.

acute coronary syndromes ; clopidogrel ; prasugrel ; ticagrelor ; percutaneous coronary intervention ; PCI ; pharmacotherapy ; hemorrhage ; heterogeneity ; medline ; guidelines ; drug-eluting stents ; receptors, purinergic p2y12 ; non-st-segment acute coronary syndromes ; NSTE-ACS ; bleeding ; 2y12 receptor antagonists ; european society of cardiology ; embase ; primary outcome measures ; pretreatment ; preloading ; loading ; NSTEMI ; unstable angina

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