A new analysis has shown that in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS) undergoing PCI, the use of prasugrel is less frequent than clopidogrel. The study, published Oct. 16 in the JACC: Cardiovascular Interventions, also showed the risk for major adverse cardiac events was significantly higher in patients with CKD than without CKD. The findings highlight the need for randomized studies evaluating the ideal antiplatelet therapy in CKD patients with ACS. 

Using data from PROMETHEUS, a multicenter observational study comparing outcomes with prasugrel vs. clopidogrel in ACS PCI patients, Usman Baber MD, MS, et al., sought to compare clinical outcomes stratified by CKD status in the 19,832 patients with data on glomerular filtration rates.

The primary endpoint of the main study was 90-day MACE, defined as a composite of death, myocardial infarction (MI), stroke or unplanned revascularization. This analysis considered all clinical endpoints at 90 days and one year. Also evaluated was stent thrombosis and clinically significant bleeding, defined as bleeding requiring hospitalization or transfusion.

CKD was identified in 28.3 percent of study patients; they were more often women, older, and had more comorbidities, such as diabetes and multivessel disease, and more likely to be treated with bare metal stents and bivalirudin. Prasugrel was prescribed about 50 percent less frequently to patients with vs. without CKD (11.0 percent vs. 24.0 percent).

At one year, CKD was associated with a greater risk of MACE (adjusted hazard ratio [HR], 1.27; p < 0.001) and clinically significant bleeding (adjusted HR, 1.46; p < 0.001). At 90 days, the adjusted HR was 1.25 (p < 0.001).

For the individual components of the MACE endpoint, there was a greater risk of MI at one year with CKD (adjusted HR, 1.36; p < 0.001). But the risk of unplanned revascularization and stent thrombosis was similar regardless of CKD status.

The study authors note their observations also fit with existing literature on higher bleeding risk in CKD patients. "This may be the result of ineffective platelets, anemia and thrombocytopenia in this mostly elderly and female patient population," the authors write. "Interestingly, assessment of platelet reactivity may allow balanced selection of CKD patients at greater ischemic risk who may benefit from potent therapies such as prasugrel without the tradeoff of greater bleeding."

In an accompanying editorial comment, Hitinder S. Gurm, MBBS, FACC, suggests the possible yet unknown benefit of using specific P2Y12 inhibitors in patients with CKD. "This double jeopardy comes into play when considering the specific choice of P2Y12 inhibitor in patients undergoing PCI for ACS since the more potent agents, ticagrelor and prasugrel, are associated with a reduction in thrombotic events and an increase in bleeding events compared with clopidogrel in the broader population," he notes. "It remains unclear whether the presence of CKD impacts the relative risk and benefit of using specific P2Y12 inhibitors."

Keywords: Acute Coronary Syndrome, Blood Platelets, omega-Chloroacetophenone, Glomerular Filtration Rate, Risk, Comorbidity, Ticlopidine, Hirudins, Peptide Fragments, Adenosine, Myocardial Infarction, Stroke, Renal Insufficiency, Chronic, Thrombocytopenia, Thrombosis, Hospitalization, Anemia, Diabetes Mellitus, Stents, Metals

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