Ticagrelor vs Clopidogrel for Patients With Acute Coronary Syndrome Undergoing Percutaneous Intervention

Abstract

To the Editor A recent retrospective cohort analysis by Dr You and colleagues 1 demonstrated that compared with clopidogrel, ticagrelor was not associated with better outcomes in patients from the US and South Korea with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). However, there are several important discrepancies between this cohort analysis and the randomized Platelet Inhibition and Patient Outcomes (PLATO) trial. 2 First, this large-scale retrospective cohort analysis included ACS patients who were considered to be at relatively low risk compared with PLATO. Approximately 80% of patients enrolled in PLATO had acute myocardial infarction (AMI), whereas the proportion of patients with AMI was more limited in this cohort analysis of databases (approximately 20% in the IQVIA Hospital, approximately 50% in the Optum EHR, and approximately 65% in the Health Insurance Review and Assessment service [HIRA]). Compared with clopidogrel, potent P2Y12 inhibitors such as ticagrelor have shown more clinical benefit in high-risk patients with enhanced thrombogenic milieu. 3 In the PLATO trial, there was no definite clinical benefit of ticagrelor vs clopidogrel in ACS patients with a normal cardiac troponin level.Second, important clinical and laboratory covariates reflecting clinical risk of patients with ACS were not included in You and colleagues' 1 propensity score model, unlike the Korea Acute Myocardial Infarction Registry-National Institutes of Health in Dual Anti-Platelet Therapy (KAMIR-NIH-DAPT) score, which uses clinical and laboratory covariates to weigh net ischemic and bleeding risks in patients with AMI. Variables in this model included cardiogenic shock, left ventricular ejection fraction less than 30%, creatinine, anemia, atrial fibrillation, multivessel disease, and complete revascularization. In patients with a KAMIR-NIH-DAPT score of 3 or higher, the use of a potent P2Y12 inhibitor showed an overall clinical benefit compared with clopidogrel without increasing bleeding events. 4 Third, the study by You and colleagues 1 did not provide sufficient data regarding coronary arterial lesional characteristics and procedural interventions; we are concerned that despite statistical adjustment, this study may not have uncovered critical confounders such as disease activity and lesion complexity. Because clopidogrel has limited antiplatelet effect to prevent atherothrombotic event occurrence in patients with AMI, potent P2Y12 inhibitors may have more clinical benefit than clopidogrel in patients treated with complex interventions or who have remnant coronary artery lesions. Recent evidence has suggested a benefit of ticagrelor vs clopidogrel for cardiac protection in high-risk patients with AMI. 5

Antiplatelet therapy in elderly patients after acute coronary syndrome

“…Various de-escalation strategies of antiplatelet therapy have been and are currently being tested: switching from a stronger to a weaker P2Y12 inhibitor, switching from dual antiplatelet therapy to monotherapy, and reducing the dose of the P2Y12 inhibitor [5][6][7][8][9].…”

De-escalation of antiplatelet therapy — an approach to improve safety and efficacy of treatment in patients after acute coronary syndrome

“…At the same time significant improvement in technology of stents and implantable scaffolds, including design, materials, and antiproliferative agents, occurred resulting in reduction of throbogenity of these devices and allowing safe shortening of DAPT if necessary [8]. Moreover, changes of platelet reactivity on treatment with P2Y12 inhibitors during the acute phase and the following stable period after ACS [9][10][11][12][13][14][15][16][17][18] is an additional factor to be considered. The complexity and ever-better understanding of the pathophysiology of ACS, as well as the ever-wider therapeutic possibilities, require a rethinking of the antiplatelet treatment strategy in this clinical setting.…”