Is Prasugrel Superior To Ticagrelor For The Treatment Of Patients With Acute Coronary Syndromes? Evidence From A 32,893-Patient Adjusted Indirect Comparison Meta-Analysis Giuseppe Biondi Zoccai, University of Turin, Turin, Italy (gbiondizoccai@gmail.com) Marzia Lotrionte, Catholic University, Rome, Italy Antonio Abbate, VCU Pauley Heart Center, Richmond, VA Pierfrancesco Agostoni, University Medical Center, Utrecht, The Netherlands Enrico Romagnoli, Policlinico Casilino, Rome, Italy Giuseppe Sangiorgi, University of Modena, Modena, Italy Imad Sheiban, University of Turin, 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 anti-thrombotic 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 (1) We searched PubMed 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 (2) Secondary end-points included components of MACE, 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 (1) 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), without differences in stroke (OR=0.90 [0.73-1.11], p=0.320) or p=0.690), despite more bleedings (OR=1.28 [1.09-1.49], and discontinuation (OR=1.08 [1.02- 1.15], p=0.01).

Results (2) 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 [0.75-1.06], 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 [0.47-1.09], 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).

Funnel plots comparing prasugrel or ticagrelor vs 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).

Funnel plots comparing prasugrel or ticagrelor vs 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)

Funnel plots comparing prasugrel vs 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. C

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.

Thank you for your attention For any correspondence: gbiondizoccai@gmail.com For these and further slides on these topics feel free to visit the metcardio.org website: http://www.metcardio.org/slides.html