Sterkere CV risicoreductie met ticagrelor bij CKD patiënten
Improved CV outcomes with ticagrelor amplified in CKD patients
A subanalysis of the PLATO trial suggests that the benefits of ticagrelor versus clopidogrel in the management of acute coronary syndrome (ACS) are evident in patients with impaired renal function.
The study showed that ACS patients with chronic kidney disease (CKD) who received ticagrelor had a reduced risk for ischemic endpoints compared with those on clopidogrel, without any increase in their risk for major bleeding. Indeed they appeared to have a greater benefit from ticagrelor treatment in terms of the primary endpoint than did patients with normal renal function.
"Ticagrelor metabolism and excretion depend minimally on renal function," explain Stefan James (Uppsala University Hospital, Sweden) and colleagues in the journal Circulation.
In the substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial, James et al analyzed the outcomes of 15,202 patients according to renal function, as determined by their creatinine clearance levels. In all, 11,965 patients had a normal renal function and 3237 had stage 3 or 4 CKD, defined as a creatinine clearance of <60 ml/min.
The researchers found that among the CKD patients, those taking ticagrelor compared with those on clopidogrel had an absolute and relative risk reduction of 4.7% and 23.0%, respectively, for the primary end point of combined CV death, myocardial infarction (MI), and stroke (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.65-0.90). Among these CKD patients, the absolute and relative risks for all-cause mortality were similarly reduced by 4% and 28%, respectively, in the patients taking ticagrelor compared with those taking clopidogrel (HR=0.72, 95% CI: 0.58-0.89).
The team found smaller risk reductions among patients with normal renal function, with nonsignificant absolute and relative risk reductions of 1% and 10%, respectively, for the primary end point (HR=0.90, 95% CI: 0.79-1.02), and 0.5% and 11%, respectively, for all-cause mortality (HR=0.89, 95% CI: 0.73-1.09).
Overall major bleeding rates did not differ significantly between the CKD and non-CKD patients, at 15.1% versus 14.3% (HR=1.07, 95% CI: 0.88-1.30). However, major bleeding rates unrelated to coronary artery bypass graft surgery were numerically higher in patients taking ticagrelor compared with those taking clopidogrel and irrespective of renal function (HR=1.28, 95% CI: 0.97-1.68).
In an accompanying editorial, Gilles Montalescot and Johanne Silvain from Pitié-Salpêtriére University Hospital in Paris, France, said that the findings of James and colleagues "translate into a number of patients who need to be treated to prevent one death of 25 CKD patients versus 200 patients without CKD." "These amazing results in patients with CKD are subjugating and need a closer look," they advised.
James et al conclude: "Given the high prevalence of renal dysfunction among patients with atherosclerotic disease… ticagrelor provides an important opportunity to substantially improve outcome in patients with ACS and impaired renal function."