Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction of ischemic events-evidence from a network meta-analysis

Abstract

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor. The comparator was standard dosage of clopidogrel. Outcomes assessed were the risk of all causes mortality, TIMI non-CABG major bleeding, and a composite of stent thrombosis, recurrent ischemia and serious recurrent ischemia in the intervention groups versus the comparator groups. Event rates were compared using a forest plot of relative risk using a random effects model (Mantel-Haenszel); and Odd's ratio was calculated in the absence of significant heterogeneity. Prasugrel was indirectly compared with ticagrelor using network meta-analysis. Four studies (total N = 34,126) met the inclusion/exclusion criteria. Both drugs had improved mortality and greater risk of bleeding compared to clopidogrel; but outcomes were comparable for both (p = NS). However a composite of recurrent ischemic events, including rates of stent thrombosis (p = 0.045) was reduced to a modest degree with prasugrel compared with ticagrelor. This systematic review suggests greater clinical efficacy of both prasugrel and ticagrelor compared with clopidogrel and an indirect comparison indicates prasugrel may be more effective than ticagrelor for preventing stent thrombosis and recurrent ischemic events.

Contemporary antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: 1‐year outcomes from the GReek AntiPlatElet (GRAPE) Registry

“…Similar trends of patient selection when prescribing novel P2Y 12 receptor antagonists over clopidogrel have been previously reported [9,10,14,18]. No clear differences in efficacy and safety outcomes between prasugrel and ticagrelor have been reported in previous meta-analyses of the randomized trials involving these agents [19][20][21]. We were also unable to reveal differences in any efficacy or safety outcome measure between prasugrel and ticagrelor-treated patients, although ticagrelor was prescribed in patients who were older, were more likely to have had a prior stroke and had more prior bleeding events than those receiving prasugrel.…”

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

“…Four published indirect comparisons [57][58][59][60] of prasugrel compared with ticagrelor were identified by the AG and the manufacturer during searching; the key features of these studies are described in Appendix 8. The quality of the four published indirect comparisons [57][58][59][60] identified by the AG (and the manufacturer) was assessed using the assessment of multiple systematic reviews (AMSTAR) 61 tool.…”

“…The quality of the four published indirect comparisons [57][58][59][60] identified by the AG (and the manufacturer) was assessed using the assessment of multiple systematic reviews (AMSTAR) 61 tool. The results are presented in Appendix 9.…”

“…The meta-analysis conducted by Chatterjee et al 58 was intended to compare prasugrel and ticagrelor in patients with ACS or those undergoing coronary intervention for the same, or for significant coronary artery disease, by conducting a network meta-analysis. 58 Four studies, comprising a total of 34,126 patients, were included: PLATO, 33 TRITON-TIMI 38, 36 DISPERSE-2 63 and JUMBO-TIMI 26.…”

“…58 Four studies, comprising a total of 34,126 patients, were included: PLATO, 33 TRITON-TIMI 38, 36 DISPERSE-2 63 and JUMBO-TIMI 26. 38 The JUMBO-TIMI 26 38 trial was a dose-ranging Phase II trial comparing prasugrel with clopidogrel in 900 patients intended for PCI.…”