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
[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 [0.751.06], 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).
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.