Influence of CKD and Thienopyridine Type in ACS PCI

Study Questions:

What are the clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status?


The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity-score stratification.


The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively, p < 0.001). At 1 year, CKD was associated with higher adjusted risk of MACE (1.27; 95% confidence interval, 1.18-1.37) and bleeding (1.46; 95% confidence interval, 1.24-1.73). Although unadjusted rates of 1-year MACE were lower with prasugrel versus clopidogrel in both CKD (18.3% vs. 26.5%, p < 0.001) and non-CKD (10.9% vs. 17.9%, p < 0.001) patients, associations were attenuated after propensity stratification. Similarly, unadjusted differences in 1-year bleeding with prasugrel versus clopidogrel (6.0% vs. 7.4%, p = 0.18 in CKD patients; 2.6% vs. 3.5%, p = 0.008 in non-CKD patients) were not significant after propensity score adjustment.


The authors concluded that risks for 1-year MACE were significantly higher in ACS PCI patients with CKD versus without CKD.


This analysis suggests that CKD patients undergoing ACS PCI have greater baseline comorbidities and significantly higher adjusted risks for 90-day and 1-year MACE, myocardial infarction, and bleeding, but not revascularization or stent thrombosis compared with those without renal impairment. Furthermore, despite the higher baseline ischemic risk, the frequency of prasugrel use was 50% lower in CKD patients, suggesting that clinical decision making regarding antiplatelet therapy is influenced to a larger extent by the potential for bleeding harm versus therapeutic efficacy. Overall, the adjusted treatment effect of prasugrel versus clopidogrel on both ischemic and bleeding events at 90 days and 1 year was uniform irrespective of CKD status in this analysis. These data highlight the need for randomized trials to guide optimal antiplatelet therapy in CKD patients with ACS undergoing PCI.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and ACS

Keywords: Acute Coronary Syndrome, Comorbidity, Diabetes Mellitus, Hemorrhage, Kidney Diseases, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists, Renal Insufficiency, Chronic, Stents, Stroke, Thrombosis, Ticlopidine

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