Ticagrelor or Clopidogrel to reduce ischemic events after Percutaneous Coronary Intervention in chronic coronary syndrome in clopidogrel naive patient: the ALPHEUS Naive sub-study
Authors: Manzo-Silberman S , Cayla G , Beygui F , Range G , Motovska Z , Vicaut E , Collet J P , Guedeney P , El Kasty M , Kerneis M , Zeitouni M , Filippi E , Coste P , Montalescot G , Silvain J 
Published: November 2023

Abstract

Background
The ALPHEUS trial showed a similar rate of type 4 myocardial infarction (MI) or major myocardial injury in elective PCI treated by clopidogrel or ticagrelor. Whether clopidogrel therapy at baseline might have affected these results is unknown.

Purpose
We evaluated the impact of ticagrelor versus clopidogrel loading dose in clopidogrel naïve patients as compared to patients already treated by clopidogrel in this pre-specified analysis.

Methods
We divided 1882 randomized patients with complete data on baseline clopidogrel into 2 groups according to presence of clopidogrel therapy &gt; 7 days (long term clopidogrel = Clopi+) or its absence (clopidogrel naïve = Clopi-). The primary endpoint was the rate of PCI-related MI and myocardial injury as defined by the 3rd and 4th universal definition of MI evaluated within 48 h of PCI (or hospital discharge if earlier) and major and minor bleeding. Angiographic complications evaluated by the core laboratory (coronary slow flow, no flow, dissection, and thrombus) were also compared. Event rates were compared and the interaction of the allocated treatment in the randomized groups was evaluated.

Results
1077 patients (57.2%) were Clopi- and 805 patients were Clopi+. Patients in the Clopi- group were less frequently male (78.0% vs 81.9%, p= 0.04) with less often dyslipidemia (57.8% vs 65.6%, p&lt; 0.001) and peripheral artery disease (11.1% vs 14.4%, p= 0.03) and had less acute coronary syndrome in the last 12 months (3.4% vs 8.7% p= 0.002). The primary endpoint was less frequent in Clopi- as compared to tClopi+ (32.8% vs 40%, OR =0.73, CI [0.60-0.88], p=0.001). This difference was mainly driven by a lower rate of major myocardial injury 24.% vs 31.6% while the rate of type 4a MI and stent thrombosis were similar (8.4% vs 8.2%) and (0.4% vs 0.2%) respectively. Angiographic complication rate was similar in the Clopi- and the Clopi+ groups (14.6% vs 12.9%) OR=1.15 CI [0.88-1.5], p=0.31. Major bleedings were infrequent in the trial. (0.1% vs 0%), and minor bleeding did not differ significantly between Clopi- and Clopi+ patients (7.0% vs 4.8% OR=1.47, CI [0.99-2.19], p=0.06). At 30 days, no difference in any outcomes were reported between the two groups. Alike for the main trial results, in the Clopi- group, ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis, p for interaction was 0.83.

Conclusions
Periprocedural MI and procedural angiographic complications were less frequent in clopidogrel naïve patients as compared to patients already on clopidogrel therapy, and not influenced by the potency of the P2Y12 inhibitor’s loading dose prior to PCI. These results globally suggest no benefit of a long term clopidogrel pretreatment in patients receiving a loading dose of P2Y12 in the 24 hours prior to PCI in chronic coronary syndrome undergoing elective PCI and support the use of clopidogrel as the standard of care.