A prespecified analysis from the ISAR-REACT 5 trial has shown that reduced renal function, compared with preserved renal function, may be associated with an increased risk for ischemic and bleeding complications among patients with chronic kidney disease (CKD) and an acute coronary syndrome (ACS) being managed with an invasive strategy. The findings will be presented during ESC Congress 2021 and were published Aug. 23 in JACC: Cardiovascular Interventions.

Jochen Wöhrle, MD, and colleagues examined the safety and efficacy of ticagrelor against prasugrel in 4,012 patients with ACS in relation to their estimated glomerular filtration rate (eGFR), categorized into three subgroups: low eGFR (<60 mL/min/1.73 m²; n=760), intermediate eGFR (between 60 and <90 mL/min/1.73 m²; n=1,968), and high eGFR (≥90 mL/min/1.73 m²; n=1,284). None of the patients in the study required dialysis.

Patients with low eGFRs were significantly older and more frequently women, and more frequently had diabetes, arterial hypertension, hypercholesterolemia, prior PCI or CABG, and cardiogenic shock. No significant difference was seen across the three subgroups for the rate of coronary angiography and the treatment strategy.

Results showed a higher risk for the primary composite outcome of all-cause death, myocardial infarction and stroke in patients with a low eGFR vs. those with an intermediate eGFR (adjusted hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.46-2.46) and vs. those with a high eGFR (adjusted HR, 2.33; 95% CI, 1.57-3.46). The risk for bleeding was also higher in the low eGFR group vs. the intermediate eGFR group (adjusted HR, 1.55; 95% CI, 1.12-2.13) and vs. the high eGFR group (HR, 1.59; 95% CI, 1.01-2.50).

Researchers found the occurrence of the primary outcome to be lower with prasugrel compared with ticagrelor across all three eGFR subgroups. In the low eGFR group, the rate for the primary endpoint was 14.7% with prasugrel vs. 20.5% with ticagrelor (HR, 1.47; 95% CI, 1.04-2.08; p=0.029). The rate of the primary endpoint with prasugrel and ticagrelor was 6.6% and 7.7% in the intermediate eGFR group (HR, 1.19; 95% CI, 0.85-1.67; p=0.30), and 2.8% and 5.2% in the high eGFR group (HR, 1.83; 95 CI, 1.03-3.25; p=0.040). No significant difference in bleeding was seen across the three eGFR subgroups.

The authors explain that their analysis of a "direct comparison of ticagrelor with prasugrel according to renal function is of great interest because of the higher ischemic and bleeding risk in patients with CKD." They conclude that their findings "suggest that renal function as assessed in this trial may not be used to guide the selection of adjunct P2Y12 inhibitors in patients with ACS."

In an accompanying editorial comment, Ovidio De Filippo, MD, et al., write that this analysis has the "merit of focusing back the scientific attention on the risk of recurrent ischemic events among CKD patients, thus helping physicians to face the crossroad of DAPT intensity in patients with impaired renal function." They add that moving forward, more data are needed to confirm these findings in patients with severe CKD and treated with hemodialysis.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Aortic Surgery, Cardiac Surgery and Heart Failure, Homozygous Familial Hypercholesterolemia, Acute Heart Failure, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension

Keywords: ESC Congress, ESC21, Purinergic P2Y Receptor Antagonists, Platelet Aggregation Inhibitors, Acute Coronary Syndrome, Glomerular Filtration Rate, Shock, Cardiogenic, Coronary Angiography, Percutaneous Coronary Intervention, Hypercholesterolemia, Renal Dialysis, Myocardial Infarction, Hemorrhage, Renal Insufficiency, Chronic, Diabetes Mellitus, Stroke, Hypertension, Coronary Artery Bypass

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