To investigate the effect of pretreatment with P2Y12 receptor inhibitors compared with no pretreatment on efficacy and safety of treatment of non-ST elevation acute coronary syndrome (ACS). The authors of this paper report the results of a pooled analysis of randomized and observational studies of pretreatment with thienopyridines (clopidogrel or prasugrel) vs no pretreatment in patients with non–ST elevation acute coronary syndromes. There was no significant reduction in mortality associated with pretreatment, although there was a significant increase in major bleeding. Therefore, the authors argue against routine pretreatment.
Thienopyridines are a class of selective, irreversible ADP receptor/P2Y12 inhibitors used for their anti-Platelet activity. Drugs in this class are: Prasugrel (Effient), Ticlopidine (Ticlid), and Clopidogrel (Plavix). Ticagrelor (Brilinta) is often listed with thienopyridine inhibitors and has similar indications for use but is not a thienopyridine. It is a cyclo-pentyltriazolo-pyrimidine that reversibly inhibits the P2Y12 receptor.
Of the 393 titles identified, seven (four randomized controlled trials, one observational analysis from a randomized controlled trial, and three observational studies) met the inclusion criteria. No study was identified for ticagrelor or cangrelor, and analyses were thus limited to thienopyridines. A total of 32 383 non-ST elevation ACS patients were included, 18 711 coming from randomized controlled trials. Of these, 55% underwent percutaneous coronary intervention (PCI). Pretreatment was not associated with a significant lower risk of mortality in all patients (odds ratio 0.90 (95% confidence interval 0.75 to 1.07), P=0.24), in particular when considering only the randomized controlled trials (odds ratio 0.90 (0.71 to 1.14), P=0.39). Similar results were observed in the cohort of patients undergoing PCI. A significant 30-45% excess of major bleeding was consistently observed in all patients (odds ratio 1.32 (1.16 to 1.49), P<0.0001) and in those undergoing PCI, as well as in the subset analyses of randomized controlled trials of these two cohorts of patients. There was a reduction in major adverse cardiovascular events in the analysis of all patients (odds ratio 0.84 (0.72 to 0.98), P=0.02), driven by the old clopidogrel studies (CURE and CREDO), but the difference was not significant for the cohort of patients undergoing PCI. Stent thrombosis, stroke, and urgent revascularization did not differ between groups (pretreatment v no pretreatment). The results were consistent for both thienopyridines and confirmed in sensitivity analyses.
Conclusion: In patients presenting with non-ST elevation ACS, pretreatment with thienopyridines is associated with no significant reduction of mortality but with a significant excess of major bleeding no matter the strategy adopted, invasive or not. In this meta-analysis of seven studies including 32,383 patients with non–ST elevation acute coronary syndrome with and without percutaneous coronary intervention, pretreatment with thienopyridines did not reduce mortality and was associated with increased risk for major bleeding (P < .0001) in all patients. The authors do not recommend routine pretreatment of patients with non–ST elevation acute coronary syndrome with thienopyridines.
A Bellemain-Appaix, M Kerneis, SA O’Connor, J Silvain, M Cucherat, F Beygui, O Barthélémy, J-P Collet, L Jacq, F Bernasconi, G Montalescot. Reappraisal of Thienopyridine Pretreatment in Patients With Non-ST Elevation Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. BMJ Oct 24, 2014.