De-escalation with clopidogrel may reduce bleeding events in patients with recent percutaneous coronary intervention

1. 12-months after randomization, the de-escalation group met the criteria for superiority (p=0.0001) with respect to the composite primary outcome of cardiovascular mortality, myocardial infarction, stroke, or bleeding.

2. Type 2, 3, or 5 bleeding was significantly less frequent in the clopidogrel group (3.0%) compared to ticagrelor group (5.6%).

Evidence Rating Level: 1 (Excellent)

Study Rundown: Antiplatelet therapy is used to mitigate the risk of recurrent thrombotic events. For this reason, ticagrelor and prasugrel – potent P2Y₁₂ inhibitors – are preferred as immediate therapy following an acute myocardial infarction. However, given their mechanism of action, these medications may also increase one’s risk for bleeding events long term. As a result, a less potent substitute, such as clopidogrel, could be explored for long-term management. This randomized controlled trial aimed to identify the effectiveness of clopidogrel as an alternative dual antiplatelet therapy (DAPT) to ticagrelor for de-escalation one month following an acute myocardial infarction. The primary outcome for this study was the occurrence of cardiovascular death, myocardial infarction, stroke, and bleeding (type 2, 3, or 5 on the Bleeding Academic Research Consortium criteria) while key secondary outcomes included all-cause mortality. According to results, the de-escalation to clopidogrel group was found to meet the noninferiority and superiority criteria for the primary outcome. In addition, de-escalation to clopidogrel resulted in fewer instances of bleeding. This study was strengthened by a large sample size with an equal proportion of patients in each group.

Click to read the study in The Lancet

Relevant Reading: Ticagrelor with or without Aspirin in High-Risk Patients after PCI

In-depth [randomized controlled trial]: Between Feb 26, 2014, and Dec 31, 2018, 2901 patients from 32 institutes in South Korea were assessed for eligibility. Included patients were those with a successful percutaneous coronary intervention (PCI) and tolerance to aspirin and ticagrelor. Altogether, 2697 patients were enrolled (1349 to aspirin plus clopidogrel [de-escalation group] and 1348 to aspirin plus ticagrelor [control group]) and 2605 completed follow-up at 12 months. All patients received aspirin and ticagrelor up to 1-month post-myocardial infarction where they were then randomized 1:1 to continue ticagrelor or de-escalate to clopidogrel. Fewer cardiovascular deaths, myocardial infarctions, strokes, or bleeding events were reported in the clopidogrel group (4.6%) compared to the ticagrelor group (8.2%) at 12 months (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.40-0.76, p_{non-inferiority}<0.001; p_superiority=0.0001). However, when looking at individual events, the only significant difference found was with type 2, 3, or 5 bleeding, which occurred less frequently in the clopidogrel group compared to ticagrelor (3.0% vs. 5.6%, HR 0.52, 95% CI 0.35-0.77, p=0.0012). Overall, findings from this study suggest that post-operative use of clopidogrel, compared to ticagrelor, may reduce bleeding events, and result in favorable clinical outcomes.

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