No reduction in ischemic events with more potent P2Y12 inhibitor in elective PCI patients
Ticagrelor Versus Clopidogrel In Elective Percutaneous Coronary Intervention : The ALPHEUS Trial
Presented at the AHA Scientific Sessions 2020 by Johanne Silvain (Paris, France)
Introduction and methods
Percutaneous coronary intervention (PCI) is a safe procedure in stable coronary patients and has a <1% chance of serious complications. However, PCI-related complications, such as MI and myocardial injury, can be frequently diagnosed after elective PCI treatment. A more potent P2Y12 inhibitor (ticagrelor) could potentially lower these ischemic events.
The Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) trial examined the effect of the P2Y12 inhibitor ticagrelor compared to clopidogrel on periprocedural myocardial ischemic events in stable coronary patients undergoing elective PCI treatment.
Patients (n=1900, <75 years) who were troponin negative or modestly positive at baseline before elective PCI were included in this study. Patients with at least one high-risk factor (eGFR <60 mL/min/1.73m², diabetes, BMI>30, history of ACS in the last 12 months, LVEF<40% and/or prior episode of HF, were randomized to loading dose of 180 mg ticagrelor or 300 mg or 600 mg clopidogrel. After PCI procedure, patients’ medication dose was adjusted to 90 mg ticagrelor twice a day or 75 mg clopidogrel daily. The primary endpoint was a composite of MI, stent thrombosis, or major myocardial injury after 48 hours (or earlier because of hospital discharge). The main secondary endpoint was a composite of minor myocardial injury or any myocardial injury. Safety was assessed by bleeding events (BARC 1-5). The follow-up for secondary endpoints was 30 days.
- There was no difference in the primary outcome, and the individual components of MI, stent thrombosis, and major myocardial injury between patients treated with ticagrelor or clopidogrel.
- There were also no differences observed in the main secondary outcome between the ones receiving ticagrelor or clopidogrel.
- Patients receiving ticagrelor had significantly more nuisance or minor bleedings (OR 1.54, 95% CI: 1.12-2.11, P=0.007) after 30 days of treatment compared to patients receiving clopidogrel. There were also more bleedings (BARC 1-5) in the ticagrelor group compared to the clopidogrel group (OR 1.58, 95% CI: 1.15-2.15, P=0.0039).
- Dyspnea occurred more frequently in patients treated with ticagrelor (11.2%) compared to the ones treated with clopidogrel (0.5%). This also led to a higher percentage of individuals on ticagrelor discontinuing the treatment (2.2% on ticagrelor vs. 0.4% on clopidogrel).
The ALPHEUS trial found no reduction on MI, stent thrombosis, and major myocardial injury with treatment of the P2Y12 inhibitor ticagrelor compared to clopidogrel in high-risk, stable coronary patients after elective PCI. Ticagrelor therapy did result in increased minor bleedings after 30 days and dyspnea occurred more frequently in patients on ticagrelor.
Discussant Stephen Wiviott (Boston, MA, USA) said that the last 25 years of anti-platelet therapy studies has resulted in more intensive antiplatelet therapy leading to a reduction in ischemic events, predominantly MI and stent thrombosis in patients undergoing PCI. But intense anti-platelet therapy also leads to increased bleeding. Wiviott emphasized that “striking a balance in individual patients and procedures results from assessing these two competing risks.”
The ACC/AHA and ESC guidelines offer recommendations on how to treat patients with acute coronary syndrome, however there is insufficient data on how to treat patients with stable coronary artery disease, said Wiviott.
This trial does not support the use of more potent P2Y12 inhibitors for elective PCI, according to Wiviott, given that there was not an ischemic benefit and a tendency of increased bleeding. Based upon these results and similar other trial outcomes (SASSICAIA), clopidogrel should remain the standard care in the treatment of stable coronary patients.
- Our reporting is based on the information provided during AHA Scientific Sessions 2020 –