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. 2022 Nov;175(11):1534-1542. doi: 10.7326/M22-1667. Epub 2022 Nov 1.

Abstract

Background: Evidence on the risk-benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent.

Objective: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment.

Design: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737).

Setting: 202 centers in China.

Patients: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.

Intervention: Ticagrelor-aspirin and clopidogrel-aspirin.

Measurements: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.

Results: Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased, and moderately to severely decreased renal function was -2.8 percentage points (95% CI, -4.4 to -1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, -2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.

Limitation: Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low.

Conclusion: Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin.

Primary funding source: Ministry of Science and Technology of the People's Republic of China.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin* / therapeutic use
  • Cerebral Infarction
  • Clopidogrel* / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics
  • Drug Therapy, Combination
  • Hemorrhage / chemically induced
  • Humans
  • Ischemic Attack, Transient* / drug therapy
  • Kidney / physiology
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Stroke / chemically induced
  • Ticagrelor* / therapeutic use
  • Treatment Outcome

Substances

  • Aspirin
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Platelet Aggregation Inhibitors
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT04078737