High on-clopidogrel platelet reactivity and chronic kidney disease: a meta-analysis of literature studies

Scand Cardiovasc J. 2019 Apr;53(2):55-61. doi: 10.1080/14017431.2019.1598571. Epub 2019 Apr 29.


Background: The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD).

Methods: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models.

Results: Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23-1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p < 0.00001), myocardial infarction (RR1.74, 95% CI 1.29 to 2.33; p = 0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p = 0.004).

Conclusions: Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.

Keywords: Chronic kidney disease; clopidogrel; high platelet reacivity.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Coronary Disease / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / epidemiology
  • Coronary Disease / therapy*
  • Drug Resistance
  • Female
  • Humans
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / physiopathology*
  • Risk Factors
  • Stents
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel