Giuseppe Biondi-Zoccai

gbiondizoccai@gmail.com

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 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.
 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
[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).
 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. 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 prasugrel, whereas odds ratios>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.