Is ticagrelor superior to prasugrel for the treatment

Background Dual antiplatelet therapy with aspirin and clopidogrel is effective and safe in patients

Aim We aimed to perform a systematic review and meta-analysis employing adjusted indirect comparison

Methods We searched Pub. Med for: ◦ randomized clinical trials ◦ reporting on the

Methods Secondary end-points included components of MACE, Academic Research Consortium definite stent thrombosis, TIMI

Results From 289 initial citations, 3 trials were finally retrieved, enrolling 32, 893 patients.

Results Head-to-head comparison of prasugrel vs. ticagrelor showed no significant differences in the risk

Comparison of prasugrel or ticagrelor vs. clopidogrel Funnel plots comparing prasugrel or ticagrelor vs.

Indirect comparison of prasugrel vs. ticagrelor Funnel plots comparing prasugrel vs. ticagrelor for the

Conclusions New antiplatelet agents such as prasugrel and ticagrelor are both more potent than

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Is ticagrelor superior to prasugrel for the treatment of acute coronary syndromes? Evidence from a 32, 893 -patient adjusted indirect comparison meta-analysis Giuseppe Biondi-Zoccai gbiondizoccai@gmail. com Division of Cardiology, University of Turin, Italy

Background Dual antiplatelet therapy with aspirin and clopidogrel is effective and safe in patients with acute coronary syndromes (ACS). Recent data suggest a superior antithrombotic efficacy of both prasugrel and ticagrelor in combination to aspirin instead of clopidogrel. However, there is yet no direct comparison of prasugrel vs. ticagrelor.

Aim We aimed to perform a systematic review and meta-analysis employing adjusted indirect comparison methods comparing prasugrel vs. ticagrelor plus aspirin in patients with ACS.

Methods We searched Pub. Med for: ◦ randomized clinical trials ◦ reporting on the comparison of prasugrel vs. clopidogrel or ticagrelor vs. clopidogrel ◦ in patients with ACS ◦ reporting on at least 1 -month events The primary end-point was the rate of major adverse cardiac events (MACE, ie death, myocardial infarction or stroke).

Methods Secondary end-points included components of MACE, Academic Research Consortium definite stent thrombosis, TIMI major bleeding (not related to CABG), and compliance. Standard and adjusted indirect comparison odds ratios (OR) were computed (with 95% confidence intervals) according to Song et al, BMJ 2003; 326: 472.

Results From 289 initial citations, 3 trials were finally retrieved, enrolling 32, 893 patients. Either prasugrel or ticagrelor appeared superior to clopidogrel for 9 -month death (OR=0. 83 [0. 74 -0. 93], p<0. 001), myocardial infarction (OR=0. 79 [0. 73 -0. 86], p<0. 001), MACE (OR=0. 83 [0. 77 - 0. 89], p<0. 001), and stent thrombosis (OR=0. 55 [0. 45 -0. 68], p<0. 001). No differences in stroke (OR=0. 90 [0. 73 -1. 11], p=0. 320) were found, despite more bleedings (OR=1. 28 [1. 09 -1. 49], and discontinuation (OR=1. 08 [1. 02 -1. 15], p=0. 01).

Results Head-to-head comparison of prasugrel vs. ticagrelor showed no significant differences in the risk of death (OR=1. 22 [0. 96 -1. 55], p=0. 106), myocardial infarction (OR=0. 89 [0. 751. 06], p=0. 202), stroke (OR=1. 19 [0. 77 -1. 84], p=0. 441), MACE (OR=0. 99 [0. 86 -1. 13], p=0. 862), stent thrombosis (OR=0. 71 [0. 471. 09], p=0. 115), or major bleeding (OR=1. 06 [0. 77 -1. 45], p=0. 738). Conversely, treatment discontinuation was more frequent with ticagrelor (OR=0. 85 [0. 72 -1. 00], p=0. 053).

Comparison of prasugrel or ticagrelor vs. clopidogrel Funnel plots comparing prasugrel or ticagrelor vs. clopidogrel for the risk of: death, myocardial infarction or stroke (A); death (B); myocardial infarction (C); stroke (D); definite or probable stent thrombosis (E).

Comparison of prasugrel or ticagrelor vs. clopidogrel Funnel plots comparing prasugrel or ticagrelor vs. clopidogrel for the risk of: major bleeding (A); major non -CABG bleeding (B); major CABG-bleeding (C); any bleeding (D); minor bleeding (E); discontinuation (F)

Indirect comparison of prasugrel vs. ticagrelor Funnel plots comparing prasugrel vs. ticagrelor for the risk of key clinical events. Odds ratios (OR) <1. 0 favor prasugrel, whereas odds ratios>1. 0 favor ticagrelor.

Conclusions New antiplatelet agents such as prasugrel and ticagrelor are both more potent than clopidogrel for patients with ACS. Head-to-head comparison suggests that they are largely similar in efficacy and safety, even if prasugrel appears more tolerated than ticagrelor.