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Poor kidney function predicts worse outcomes in acute coronary syndrome (ACS) but not less benefit of prasugrel (Effient) over ticagrelor (Brilinta) in dual antiplatelet therapy for those headed to the cath lab, an analysis of the ISAR-REACT 5 trial showed.

Among the more than 4,000 patients in the open-label trial, the main findings still held across kidney function ranges, with no interaction between randomized study drug and estimated glomerular filtration rate (eGFR) for either the primary efficacy endpoint (P=0.41) or BARC types 3 to 5 bleeding (P=0.92), according to Jochen Wöhrle, MD, of the Medical Campus Lake Constance in Friedrichshafen, Germany, and colleagues, writing in .

Ticagrelor had a relative 47% more primary endpoint events than prasugrel in the chronic kidney disease (CKD, eGFR <60 mL/min/1.73 m²) group (P=0.029), a non-significant difference in the intermediate eGFR group (HR 1.19, P=0.30), and a relative 83% more primary endpoint events in the normal eGFR group (P=0.04).

"These 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," the authors concluded.

As expected, though, low eGFR predicted both ischemic and bleeding events overall in the prespecified analysis published ahead of presentation at the European Society of Cardiology virtual meeting.

The 760 patients with CKD had significantly higher risk of the primary trial endpoint, a composite of 1-year stroke, MI, or death: adjusted HR 1.89 versus more mildly decreased eGFR and 2.33 versus normal eGFR. CKD patients also had higher bleeding risk (aHR 1.55 and 1.59, respectively).

CKD "represents a puzzling dilemma" in ACS care, with prior studies documenting such patients less often get optimal medical therapy and potent P2Y₁₂ inhibitors, Ovidio De Filippo, MD, of A.O.U Città della Salute e della Scienza di Torino in Italy, and colleagues wrote in an .

"Although eGFR was not a randomization criterion in the main trial," they noted that "the study provides the largest cohort of patients with kidney dysfunction randomized to either prasugrel or ticagrelor."

Indeed, the researchers noted: "Because of the particularly high risk for adverse ischemic and bleeding events in patients with low eGFRs, this subgroup of patients also provides an excellent setting for the assessment of differences in treatment effect on rare events between ticagrelor and prasugrel."

The results weren't surprising given the main trial findings and available pharmacokinetic evidence, the editorialists added. "Ticagrelor metabolism indeed minimally depends on renal function, while previous studies observed that the levels of the active metabolites of prasugrel were not affected by moderate renal impairment."

Part of the study's importance might be just focusing back attention onto recurrent ischemic events among CKD patients, they argued.

Less concern over stent thrombosis with new-generation drug-eluting stents and potent antiplatelet therapies has "unconsciously led to a kind of neglect for the risk of recurrent ischemic events while a growing attention has been paid to bleeding outcomes and their impact on prognosis," De Filippo's group noted.

The researchers cautioned that the findings should be considered hypothesis generating because there was no eGFR-based stratified randomization of the participants.

The editorialists also pointed to the low sample size in each eGFR subgroup and called for further research to confirm the findings would hold among patients with severe CKD and those treated with hemodialysis, as ISAR-REACT 5 excluded those with CKD requiring dialysis.