Renal Function Impacts Efficacy of Dual-Antiplatelet Therapy After Minor Stroke

Compared with patients with impaired renal function, those with normal renal function demonstrated greater benefit with ticagrelor-aspirin compared with clopidogrel-aspirin.

Following a minor stroke or transient ischemic attack (TIA), patients with normal renal function treated with ticagrelor-aspirin had a lower risk for stroke at 90 days compared with clopidogrel-aspirin. These are the findings of a study published in the Annals of Internal Medicine.

Researchers conducted a post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial, Clopidogrel With Aspirin in High-Risk Patients With Acute Non-disabling Cerebrovascular Events II (CHANCE-2; Identifier: NCT04078737) across 202 medical centers throughout China. They compared the efficacy and safety of the dual-antiplatelet therapies, ticagrelor-aspirin and clopidogrel-aspirin, used to treat 6378 patients (aged 40 years or older; 33.9% women) following minor stroke or TIAs.

In the CHANCE-2 trial, researchers randomly assigned patients to 2 treatment groups after experiencing a minor stroke or TIA — 3187 to receive ticagrelor-aspirin and 3191 to receive clopidogrel-aspirin.

The researchers focused on the effect of these 2 treatments on renal function as measured by estimated glomerular filtration rate (eGFR). Additionally, they analyzed stroke recurrence and moderate to severe bleeding within 90 days of the initial stroke or TIA.

Of the 6378 patients studied, 4050 demonstrated normal renal function (eGFR ≥ 90 mL/min/1.73m2), while 2010 and 318 patients exhibited mildly decreased (eGFR 60-89 mL/min/1.73m2) and moderately to severely decreased (eGFR <60 mL/min/1.73m2) renal function, respectively.

Potential mechanisms underlying our results may be a synergistic relationship between the thrombotic effects of renal dysfunction and the antithrombotic effects of dual antiplatelet treatment.

Recurrent stroke occurred in 189 patients (5.9%) treated with ticagrelor-aspirin and 243 patients (7.6%) treated with clopidogrel-aspirin.

In patients with normal renal function, ticagrelor-aspirin correlated with reduced recurrence of stroke within 90 days compared with clopidogrel-aspirin (5.2% vs. 8.1%, respectively; difference: -2.8%; 95% CI, -4.4% to -1.3%; hazard ratio [HR], 0.63; 95% CI, 0.49-0.81). This trend between treatment groups was not observed in patients with mild or moderate-to-severe renal impairment.

Moderate or severe bleeding rate did not differ significantly across the renal impairment categories between the 2 treatment groups.

“Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor–aspirin versus clopidogrel–aspirin,” the researchers noted. “Potential mechanisms underlying our results may be a synergistic relationship between the thrombotic effects of renal dysfunction and the antithrombotic effects of dual antiplatelet treatment,” they hypothesized.

Study limitations included definition of renal function using only eGFR without including measurements of proteinuria or albuminuria, decreased number of patients with moderate to severe renal impairment, and the inability to generalize results outside of the Chinese population.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.


Wang A, Xie X, Tian X, et al. Ticagrelor-aspirin versus clopidogrel-aspirin among CYP2C19 loss-of-function carriers with minor stroke or transient ischemic attack in relation to renal function: A post hoc analysis of the CHANCE-2 trial. Ann Intern Med. Published online November 1, 2022. doi:10.7326/M22-1667