Clopidogrel plus aspirin lowers risk for second stroke in normal renal function
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After a minor stroke or transient ischemic attack, patients with normal vs. impaired renal function treated with ticagrelor plus aspirin had lower risk for stroke at 90 days compared with clopidogrel plus aspirin, researchers reported.
The findings of a post hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial were published in the Annals of Internal Medicine.
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"Based on the CHANCE-2 trial, our study showed that among CYP2C19 [loss-of-function] carriers with minor stroke or TIA, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with a reduced risk for recurrent stroke and without any substantial increase in severe or moderate bleeding events among patients with normal renal function, whereas patients with impaired renal function did not derive the same benefit from ticagrelor-aspirin," Anxin Wang, PhD, of the department of neurology at Beijing Tiantan Hospital and the National Clinical Research Center for Neurological Diseases in Beijing, and colleagues wrote. "The findings suggest that renal function should be considered when deciding on the use of ticagrelor-aspirin vs. clopidogrel-aspirin."
The CHANCE-2 trial
CHANCE-2 was a multicenter, randomized controlled trial conducted in China that enrolled 6,412 patients who were aged 40 years or older with a minor stroke or TIA and were carriers of CYP2C19 loss-of-function alleles. Within 24 hours of symptom onset, participants were given ticagrelor (Brilinta, AstraZeneca) plus aspirin or clopidogrel plus aspirin. Ticagrelor plus aspirin cut risk for stroke at 90 days modestly compared with clopidogrel plus aspirin and the bleeding risk did not differ between the two treatments, according to the findings published in The New England Journal of Medicine.
CHANCE-2 post hoc analysis
For the post hoc analysis, Wang and colleagues evaluated whether patient renal function had any effect on the efficacy and safety of treatment with ticagrelor plus aspirin compared with clopidogrel plus aspirin in the CHANCE-2 cohort.
The primary efficacy outcome was new hemorrhagic or ischemic stroke within 90 days and the primary safety outcome was Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding.
Within the CHANCE-2 cohort, 63.5% of participants had normal renal function (estimated glomerular filtration rate [eGFR] 90 mL/min/1.73 m2), 31.5% had mildly decreased renal function (eGFR 60-89 mL/min/1.73 m2) and 5% had moderately to severely decreased renal function (eGFR < 60 mL/min/1.73 m2).
Researchers observed that compared with patients with impaired renal function, those with normal renal function derived greater benefit with regard to the primary outcome from ticagrelor plus aspirin compared with clopidogrel plus aspirin:
- normal renal function (HR = 0.63; 95% CI, 0.49-0.81);
- mildly decreased renal function (HR = 0.98; 95% CI, 0.69-1.39); and
- moderately to severely decreased renal function (HR = 1.31; 95% CI, 0.48-3.55).
The rate of severe or moderate bleeding was not significantly different between treatment assignments and across eGFR categories, according to the study.
“Decreased renal function is characterized as a state with a prothrombotic tendency, and is associated with anemia, homocysteinemia, reduced nitric oxide, oxidative stress, inflammation, and conditions promoting coagulation; all of these pathologic processes may be related to the development of recurrent stroke in the course of decreased renal function,” the researchers wrote. “The levels of platelet inhibition from different antiplatelet therapies may not be sufficient for adequate protection against ischemic events in these patients at high risk.”
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