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Abstract: SA-PO259

Use of Antiplatelet Drugs Targeting Platelet P2Y12 Receptor Is Associated with Reduced Risk for Infectious Death in Veterans with CKD

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Jain, Nishank, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Shrestha, Prabin, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Thomas, Fridtjof, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Lu, Jun Ling, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kalantar-Zadeh, Kamyar, University of California Los Angeles, Los Angeles, California, United States
  • Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Platelets modulate thrombosis and inflammation, a hallmark of CKD pathophysiology. As a result, antiplatelet drugs are commonly used to reduce the risk of thrombosis in patients with CKD. Recent studies also demonstrated that platelet P2Y12 receptor inhibitors (P2Y12i) reduce inflammatory burden in patients with CKD, but their clinical impact on inflammation-related outcomes in CKD is not established. We investigated whether treatment with P2Y12i is associated with reduction in infection related deaths among patients with CKD.

Methods

We examined a national cohort of 90,701 US Veterans with incident CKD who were new P2Y12i users and 431,188 who never received P2Y12i. We used clinical trial emulation methods to examine the association of P2Y12i therapy with infectious deaths in competing risk regressions and cause-specific Cox models using propensity score (PS) overlap weighting to balance for baseline differences in demographics, comorbidities, laboratory values, and relevant medications use.

Results

Overall mean (SD) age was 69 (11) years, and eGFR was 69 (17) ml/min/1.73m2; 95% were men; 16% were African Americans; 46% were diabetics. During a median follow-up of 6.8 years, there were 4,823 infectious deaths with 986 deaths in P2Y12i users (event rate and 95%CI: 0.87/1000PY, 0.82-0.92) and 3,837 deaths in non-users (1.45/1000PY, 1.4-1.5). P2Y12i therapy was associated with a reduced risk of infectious deaths in competing risk regressions and in cause-specific Cox models (Table).

Conclusion

In a large national cohort of Veterans with incident CKD, use of P2Y12i was associated with reduced risk of infectious deaths. The role of P2Y12i in the management of inflammation in CKD requires additional testing in prospective trials.

Subhazard ratio and hazard ratio of a PS-weighed competing risk and cause specific Cox model in P2Y12i treated patients (vs. untreated) (n=521889).
  Competing RiskP-valueCox ModelP-value
 Event Rate per 1000PY (95% CI)Subhazard Ratio
(95% CI)
 Hazard Ratio
(95% CI)
 
No P2Y12i Treatment (N=431,188)1.45 (1.4, 1.5)Referent0.0016Referent<0.0001
P2Y12i Treatment (N=90,701)0.87 (0.82, 0.92)0.72 (0.58, 0.88)0.45 (0.36, 0.57)

Funding

  • Veterans Affairs Support