Impact of different P2Y12 inhibitors in acute coronary syndrome patients with severe chronic kidney disease: insights from the CORALYS registry

Abstract Background The impact of the most potent P2Y12i ticagrelor and prasugrel after acute coronary syndrome in patients with chronic kidney disease (CKD) remains unclear. Most evidence on dual antiplatelet therapy (DAPT) comes from real-world study but is limited to glomerular filtration rate (GFR) under 60 ml/min whereas no data are available regarding patients with severe CKD (stages IV-V) Methods Consecutive patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and severe CKD defined as GFR under 30 ml/min not on dialysis from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of Net Adverse Clinical Events (NACE) defined as major adverse cardiac events (MACE, a composite of cardiovascular death, myocardial infarction and unplanned revascularizations) in addition to major bleedings (classified as BARC scale 3 to 5) was our primary endpoint. Overall MACE and their single components, all bleedings, major bleedings and hospitalizations for heart failure were the secondary ones. Results Of 14699 patients in the CORALYS registry, 257 presented with severe CKD not on dialysis and had available data on antiplatelet regimen at discharge. Patients were divided into two groups according to the type of P2Y12i prescribed at discharge: 193 (75.1%) were given clopidogrel while 64 (24.9%) with ticagrelor or prasugrel. Our populaiton was predominantly male (153, 59.5%) with an average age 75.8 ± 10.9 years old. Average GFR was 21.8 ± 6.3 ml/min. Over a median follow-up of 459 days, Ticagrelor and Prasugrel were associated to lower rates of NACE compared to Clopidogrel (39.9% vs 25.0%, p=0.036). This was mainly driven by an excess of both CV mortality (31.1% vs 6.3%) and myocardial infarction (20.7% vs 9.4%) reported in the clopidogrel group. No difference was reported regarding overall bleeding events (5.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.81) and major bleedings (1.7% vs 4.6% with clopidogrel and new P2Y12i respectively, p=0.15). At multivariate Cox regression analysis DAPT with Ticagrelor/Prasugrel resulted independently associated with a lower risk of NACE (Adj Hr 0.41, 95%CI 0.23-0.74, p=0.003) whereas left main involvement or multivessel coronary disease led to higher risk of NACE (Adj HR 1.96 95%CI 1.21-3.18, p=0.006) Conclusions In ACS patients treated with PCI with severe CKD ticagrelor and prasugrel were associated to lower risk of NACE, MACE, CV death and myocardial infarction compared to clopidogrel. No significative difference was reported in overall and major bleedings despite a relative increase of major bleedings in the group treated with Ticagrelor or Prasugrel.