Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.
BACKGROUND
Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.


RESULTS
Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant.


CONCLUSIONS
In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.


BACKGROUND
URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.
James
Stefan
S
Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden. Stefan.james@ucr.uu.se
Budaj
Andrzej
A
Aylward
Philip
P
Buck
Kristen K
KK
Cannon
Christopher P
CP
Cornel
Jan H
JH
Harrington
Robert A
RA
Horrow
Jay
J
Katus
Hugo
H
Keltai
Matyas
M
Lewis
Basil S
BS
Parikh
Keyur
K
Storey
Robert F
RF
Szummer
Karolina
K
Wojdyla
Daniel
D
Wallentin
Lars
L
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D002908:Chronic Disease; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine