Giuseppe Biondi-Zoccai Division of Cardiology, University of Turin, Turin, Italy.

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Presentation transcript:

Giuseppe Biondi-Zoccai Division of Cardiology, University of Turin, Turin, Italy

 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.

 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.

 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).

 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.

 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 [ ], p<0.001), myocardial infarction (OR=0.79 [ ], p<0.001), MACE (OR=0.83 [ ], p<0.001), and stent thrombosis (OR=0.55 [ ], p<0.001).  No differences in stroke (OR=0.90 [ ], p=0.320) were found, despite more bleedings (OR=1.28 [ ], and discontinuation (OR=1.08 [ ], p=0.01).

 Head-to-head comparison of prasugrel vs. ticagrelor showed no significant differences in the risk of death (OR=1.22 [ ], p=0.106), myocardial infarction (OR=0.89 [ ], p=0.202), stroke (OR=1.19 [ ], p=0.441), MACE (OR=0.99 [ ], p=0.862), stent thrombosis (OR=0.71 [ ], p=0.115), or major bleeding (OR=1.06 [ ], p=0.738).  Conversely, treatment discontinuation was more frequent with ticagrelor (OR=0.85 [ ], p=0.053).

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. 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. ticagrelor for the risk of key clinical events. Odds ratios (OR) 1.0 favor ticagrelor.

 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.