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 firstname.lastname@example.org Division of Cardiology, 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 • 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 • 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 [0.75-1.06], 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).
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)
Indirectcomparison 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.